Pub Date : 2025-11-26DOI: 10.1016/j.mvr.2025.104886
B. Gayathri , K. Sreekanth , G. Aparna , C. Chandana , N. Radhakrishnan , E.K. Radhakrishnan
Angioplasty and coronary artery bypass grafting (CABG) are common interventions for the management of coronary artery disease aiming to address atherosclerotic plaques in the epicardial coronary arteries. However, many patients experience recurrent angina and other complications such as low cardiac output and even mortality due to other undiagnosed pathologies. Coronary microvascular dysfunction (CMD), which causes impaired blood flow in the microvascular network is a critically overlooked factor in this regard. Such microvascular dysfunction occurs due to the endothelial abnormalities leading to vascular remodelling, and increased resistance to blood flow. The mobilization of unstable plaques during operative procedures such as stenting, angioplasty, and bypass surgery can also contribute to the microcirculatory obstruction, potentially resulting in fatal coronary embolization. Also, such plaque rupture release emboli that can migrate and obstruct the distal arterioles, resulting in low cardiac output, recurrent angina, and ischemia. These microvascular blocks resulting from preexisting dysfunction or iatrogenic embolization are mostly undiagnosed after a CABG or angioplasty. Diagnosis of CMD is challenging, as conventional imaging techniques only focus on macrovascular assessment, neglecting the importance of microvascular hemodynamics. Current diagnostic protocols need a re-evaluation to include methods to assess microvascular perfusion dynamics in postoperative patients.
{"title":"The underdiagnosed risk of Coronary microvascular dysfunction in post CABG/angioplasty patients a call for myocardial perfusion mapping of blood flow dynamics","authors":"B. Gayathri , K. Sreekanth , G. Aparna , C. Chandana , N. Radhakrishnan , E.K. Radhakrishnan","doi":"10.1016/j.mvr.2025.104886","DOIUrl":"10.1016/j.mvr.2025.104886","url":null,"abstract":"<div><div>Angioplasty and coronary artery bypass grafting (CABG) are common interventions for the management of coronary artery disease aiming to address atherosclerotic plaques in the epicardial coronary arteries. However, many patients experience recurrent angina and other complications such as low cardiac output and even mortality due to other undiagnosed pathologies. Coronary microvascular dysfunction (CMD), which causes impaired blood flow in the microvascular network is a critically overlooked factor in this regard. Such microvascular dysfunction occurs due to the endothelial abnormalities leading to vascular remodelling, and increased resistance to blood flow. The mobilization of unstable plaques during operative procedures such as stenting, angioplasty, and bypass surgery can also contribute to the microcirculatory obstruction, potentially resulting in fatal coronary embolization. Also, such plaque rupture release emboli that can migrate and obstruct the distal arterioles, resulting in low cardiac output, recurrent angina, and ischemia. These microvascular blocks resulting from preexisting dysfunction or iatrogenic embolization are mostly undiagnosed after a CABG or angioplasty. Diagnosis of CMD is challenging, as conventional imaging techniques only focus on macrovascular assessment, neglecting the importance of microvascular hemodynamics. Current diagnostic protocols need a re-evaluation to include methods to assess microvascular perfusion dynamics in postoperative patients.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"164 ","pages":"Article 104886"},"PeriodicalIF":2.7,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-14DOI: 10.1016/j.mvr.2025.104884
Jin Zhou , Xiaomin Hou , Zhifa Zheng , Tingting Quan , Xin Meng , Yi Xu , Liangyuan Zhao , Xiaoxia Ren , Lingbo Yang , Yiwei Shi , Xiaojiang Qin
Pulmonary hypertension (PH) is a severe and life-threatening pulmonary vascular disease. Cigarette smoking is a significant environmental risk factor for PH, and nicotine, a primary toxic component of cigarettes, is closely associated with the development and progression of PH. This study aimed to elucidate the pathological progression of PH induced by chronic nicotine exposure and its dose-dependent effects. We established a murine model of PH by intranasal nicotine instillation in C57BL/6 J mice, coupled with a clinical cohort study of smokers. Using high-resolution echocardiography, right heart catheterization, microvascular tension measurement, and histopathological techniques, we systematically assessed nicotine's dose-dependent effects on pulmonary hemodynamics, vascular function, and cardiac structure and function. Results demonstrated right ventricular systolic pressure (RVSP)—a surrogate for pulmonary arterial (PA) systolic pressure without pulmonary valve stenosis—increased from 18.09 ± 0.28 mmHg (Control) to 31.99 ± 0.21 mmHg (High-dose, P < 0.01). RV hypertrophy and dilation were accompanied by dose-dependent impairment in tricuspid annular plane systolic excursion (TAPSE), declining from 1.83 ± 0.05 mm to 1.15 ± 0.03 mm (P < 0.01). PA abnormalities included shortened acceleration time (PAT), reduced PAT/ejection time ratio, increased PA diameter (PAD), vascular wall thickening, and inflammatory infiltration. Microvascular tension studies confirmed functional impairment. Clinical validation mirrored core findings: in PH patients, smoking index correlated positively with PAD (R2 = 0.8553, P < 0.01) and negatively with TAPSE (R2 = 0.7523, P < 0.01), strongly corroborating animal data and underscoring nicotine's clinical hazards. Our research demonstrates chronic nicotine exposure induces dose-dependent PH through elevated PA pressure, pulmonary vascular remodeling, and RV dysfunction, providing mechanistic insights for smoking-related PH prevention and treatment.
{"title":"Chronic nicotine exposure drives dose-dependent pulmonary hypertension and cardiopulmonary remodeling: Preclinical and clinical validation","authors":"Jin Zhou , Xiaomin Hou , Zhifa Zheng , Tingting Quan , Xin Meng , Yi Xu , Liangyuan Zhao , Xiaoxia Ren , Lingbo Yang , Yiwei Shi , Xiaojiang Qin","doi":"10.1016/j.mvr.2025.104884","DOIUrl":"10.1016/j.mvr.2025.104884","url":null,"abstract":"<div><div>Pulmonary hypertension (PH) is a severe and life-threatening pulmonary vascular disease. Cigarette smoking is a significant environmental risk factor for PH, and nicotine, a primary toxic component of cigarettes, is closely associated with the development and progression of PH. This study aimed to elucidate the pathological progression of PH induced by chronic nicotine exposure and its dose-dependent effects. We established a murine model of PH by intranasal nicotine instillation in C57BL/6 J mice, coupled with a clinical cohort study of smokers. Using high-resolution echocardiography, right heart catheterization, microvascular tension measurement, and histopathological techniques, we systematically assessed nicotine's dose-dependent effects on pulmonary hemodynamics, vascular function, and cardiac structure and function. Results demonstrated right ventricular systolic pressure (RVSP)—a surrogate for pulmonary arterial (PA) systolic pressure without pulmonary valve stenosis—increased from 18.09 ± 0.28 mmHg (Control) to 31.99 ± 0.21 mmHg (High-dose, <em>P</em> < 0.01). RV hypertrophy and dilation were accompanied by dose-dependent impairment in tricuspid annular plane systolic excursion (TAPSE), declining from 1.83 ± 0.05 mm to 1.15 ± 0.03 mm (<em>P</em> < 0.01). PA abnormalities included shortened acceleration time (PAT), reduced PAT/ejection time ratio, increased PA diameter (PAD), vascular wall thickening, and inflammatory infiltration. Microvascular tension studies confirmed functional impairment. Clinical validation mirrored core findings: in PH patients, smoking index correlated positively with PAD (R<sup>2</sup> = 0.8553, <em>P</em> < 0.01) and negatively with TAPSE (R<sup>2</sup> = 0.7523, <em>P</em> < 0.01), strongly corroborating animal data and underscoring nicotine's clinical hazards. Our research demonstrates chronic nicotine exposure induces dose-dependent PH through elevated PA pressure, pulmonary vascular remodeling, and RV dysfunction, providing mechanistic insights for smoking-related PH prevention and treatment.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104884"},"PeriodicalIF":2.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/j.mvr.2025.104885
Xiao Xu , Xiaohu Ge , Hongbo Ci , Maitiseyiti Abulaihaiti , JianPing Yang , YangYang Li , Feng Zhu
Background
Thromboangiitis obliterans (TAO, Buerger's disease) is a chronic inflammatory disorder that affects small and medium-sized vessels in the limbs. Although the pathogenesis of TAO remains incompletely understood, elevated levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with cardiovascular diseases. This study investigates the mechanism by which PAI-1 activates the NF-κB/NLRP3 inflammatory pathway in vascular endothelial cells through hypoxia-inducible factor-1α (HIF-1α), contributing to the progression of TAO.
Methods
Proteomic analysis was performed on plasma samples from 5 TAO patients and 5 healthy controls to identify differentially expressed proteins (DEPs). In vitro, human umbilical vein endothelial cells (HUVECs) were subjected to 1 % hypoxia to mimic TAO conditions. Interventions included PAI-1 knockdown using lentiviral vectors and treatment with the HIF-1α agonist dimethyloxalylglycine (DMOG). Cell viability was assessed using the CCK-8 assay, apoptosis was measured by flow cytometry, and inflammatory factor levels were detected by enzyme-linked immunosorbent assay (ELISA). Protein expression was analyzed by Western blotting. In vivo, a TAO rat model was established by sodium laurate injection. The severity of limb ischemia was evaluated using gross lesion grading and infrared thermography, while pathological changes were assessed by hematoxylin and eosin (H&E) staining and Masson's trichrome staining.
Results
Elevated levels of PAI-1, HIF-1α, and key molecules in the NLRP3/NF-κB pathway were observed in both TAO rats and hypoxic HUVECs. PAI-1 knockdown significantly improved limb ischemia and suppressed the NLRP3/NF-κB pathway in TAO rats. Compared with the DMOG intervention group, combined treatment with PAI-1 knockdown and DMOG effectively alleviated ischemic symptoms, increased body weight, and reduced the expression of HIF-1α and inflammatory pathway molecules in TAO rats.
Conclusion
PAI-1 promotes the progression of TAO by activating the NF-κB pathway via HIF-1α. Targeted inhibition of PAI-1 represents a potential therapeutic strategy for TAO.
{"title":"PAI-1 promotes thromboangiitis obliterans progression through NF-κB-NLRP3 pathway activation via HIF-1α-dependent signaling","authors":"Xiao Xu , Xiaohu Ge , Hongbo Ci , Maitiseyiti Abulaihaiti , JianPing Yang , YangYang Li , Feng Zhu","doi":"10.1016/j.mvr.2025.104885","DOIUrl":"10.1016/j.mvr.2025.104885","url":null,"abstract":"<div><h3>Background</h3><div>Thromboangiitis obliterans (TAO, Buerger's disease) is a chronic inflammatory disorder that affects small and medium-sized vessels in the limbs. Although the pathogenesis of TAO remains incompletely understood, elevated levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with cardiovascular diseases. This study investigates the mechanism by which PAI-1 activates the NF-κB/NLRP3 inflammatory pathway in vascular endothelial cells through hypoxia-inducible factor-1α (HIF-1α), contributing to the progression of TAO.</div></div><div><h3>Methods</h3><div>Proteomic analysis was performed on plasma samples from 5 TAO patients and 5 healthy controls to identify differentially expressed proteins (DEPs). In vitro, human umbilical vein endothelial cells (HUVECs) were subjected to 1 % hypoxia to mimic TAO conditions. Interventions included PAI-1 knockdown using lentiviral vectors and treatment with the HIF-1α agonist dimethyloxalylglycine (DMOG). Cell viability was assessed using the CCK-8 assay, apoptosis was measured by flow cytometry, and inflammatory factor levels were detected by enzyme-linked immunosorbent assay (ELISA). Protein expression was analyzed by Western blotting. In vivo, a TAO rat model was established by sodium laurate injection. The severity of limb ischemia was evaluated using gross lesion grading and infrared thermography, while pathological changes were assessed by hematoxylin and eosin (H&E) staining and Masson's trichrome staining.</div></div><div><h3>Results</h3><div>Elevated levels of PAI-1, HIF-1α, and key molecules in the NLRP3/NF-κB pathway were observed in both TAO rats and hypoxic HUVECs. PAI-1 knockdown significantly improved limb ischemia and suppressed the NLRP3/NF-κB pathway in TAO rats. Compared with the DMOG intervention group, combined treatment with PAI-1 knockdown and DMOG effectively alleviated ischemic symptoms, increased body weight, and reduced the expression of HIF-1α and inflammatory pathway molecules in TAO rats.</div></div><div><h3>Conclusion</h3><div>PAI-1 promotes the progression of TAO by activating the NF-κB pathway via HIF-1α. Targeted inhibition of PAI-1 represents a potential therapeutic strategy for TAO.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104885"},"PeriodicalIF":2.7,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-05DOI: 10.1016/j.mvr.2025.104883
Jiang Hugang , Liu Ai , Guo Zeao , Ren Chunzhen , Lin Wenyan , Liu Kai , Zhao Xinke , Li Yingdong
Background
Coronary Microvascular Dysfunction (CMVD), a prevalent comorbidity of various cardiovascular diseases, may contribute to myocardial cell ischemic necrosis. The loss of microvessels—driven by endothelial cells (ECs) apoptosis—is the core pathological hallmarks of CMVD. Our previous studies have established that RAS-RH (Angelica sinensis and Astragalus membranaceus ultrafiltrate) promotes angiogenesis and improves cardiac perfusion. However, its underlying molecular mechanisms remain incompletely understood.
Purpose
This study aimed to elucidate the key mechanism by which quercetin, the primary active component of RAS-RH, modulates radiation-induced ECs apoptosis.
Methods
Through the integration of network pharmacology and transcriptomics, we identified potential active components of RAS-RH and their key targets involved in regulating the telocytes-endothelial cell (TCs-ECs) crosstalk pathway underlying CMVD. These predictions were further validated using in vitro cellular models via flow cytometry, western blot, wound-healing assays, in situ hybridization, immunofluorescence staining, and EdU proliferation assays.
Results
Consistent with our predictions, experimental results demonstrated that quercetin (the primary active component of RAS-RH) significantly upregulated the expression of HIF-1α and miRNA-126 in TCs (P < 0.01) and enhanced miRNA-126 paracrine secretion. Through this paracrine mechanism, quercetin downregulated the expression of Cypd, ANT, F1F0-ATPase, and VDAC in ECs (P < 0.01), inhibited the reduction of mitochondrial membrane potential (ΔΨm) and ECs apoptosis induced by excessive mPTP opening. Collectively, these effects enhanced ECs proliferation, migration, and tube formation capacity, ultimately promoting angiogenesis.
Conclusion
These results collectively demonstrate that quercetin, the primary active component of RAS-RH, suppresses excessive mPTP activation and apoptosis while stimulating ECs migration and tube formation. This occurs via upregulating HIF-1α and miRNA-126 expression in TCs and enhancing miRNA-126 paracrine to ECs, positioning the TCs-ECs crosstalk mechanism as a promising novel therapeutic target for intervening in coronary microcirculation dysfunction.
{"title":"Mechanistic investigation of quercetin (an active component of RAS-RH) in modulating radiation-induced coronary microvascular dysfunction via the TCs-ECs crosstalk pathway","authors":"Jiang Hugang , Liu Ai , Guo Zeao , Ren Chunzhen , Lin Wenyan , Liu Kai , Zhao Xinke , Li Yingdong","doi":"10.1016/j.mvr.2025.104883","DOIUrl":"10.1016/j.mvr.2025.104883","url":null,"abstract":"<div><h3>Background</h3><div>Coronary Microvascular Dysfunction (CMVD), a prevalent comorbidity of various cardiovascular diseases, may contribute to myocardial cell ischemic necrosis. The loss of microvessels—driven by endothelial cells (ECs) apoptosis—is the core pathological hallmarks of CMVD. Our previous studies have established that RAS-RH (<em>Angelica sinensis</em> and <em>Astragalus membranaceus</em> ultrafiltrate) promotes angiogenesis and improves cardiac perfusion. However, its underlying molecular mechanisms remain incompletely understood.</div></div><div><h3>Purpose</h3><div>This study aimed to elucidate the key mechanism by which quercetin, the primary active component of RAS-RH, modulates radiation-induced ECs apoptosis.</div></div><div><h3>Methods</h3><div>Through the integration of network pharmacology and transcriptomics, we identified potential active components of RAS-RH and their key targets involved in regulating the telocytes-endothelial cell (TCs-ECs) crosstalk pathway underlying CMVD. These predictions were further validated using in vitro cellular models via flow cytometry, western blot, wound-healing assays, in situ hybridization, immunofluorescence staining, and EdU proliferation assays.</div></div><div><h3>Results</h3><div>Consistent with our predictions, experimental results demonstrated that quercetin (the primary active component of RAS-RH) significantly upregulated the expression of HIF-1α and miRNA-126 in TCs (<em>P</em> < 0.01) and enhanced miRNA-126 paracrine secretion. Through this paracrine mechanism, quercetin downregulated the expression of Cypd, ANT, F1F0-ATPase, and VDAC in ECs (<em>P</em> < 0.01), inhibited the reduction of mitochondrial membrane potential (ΔΨm) and ECs apoptosis induced by excessive mPTP opening. Collectively, these effects enhanced ECs proliferation, migration, and tube formation capacity, ultimately promoting angiogenesis.</div></div><div><h3>Conclusion</h3><div>These results collectively demonstrate that quercetin, the primary active component of RAS-RH, suppresses excessive mPTP activation and apoptosis while stimulating ECs migration and tube formation. This occurs via upregulating HIF-1α and miRNA-126 expression in TCs and enhancing miRNA-126 paracrine to ECs, positioning the TCs-ECs crosstalk mechanism as a promising novel therapeutic target for intervening in coronary microcirculation dysfunction.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104883"},"PeriodicalIF":2.7,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-02DOI: 10.1016/j.mvr.2025.104882
Jing Zhang , Zishu Yang , Li Liu , Di Wu , Chen Cheng , Peng Zhu , Wei Wang , Wenqiang Li , Hua Deng , Yudiyang Ma , Cuiyuan Huang , Jian Yang
Background
Hyperinsulinemia-induced inflammatory responses are a key pathological basis for diabetic proliferative vascular lesions. However, DOT1L impact on vascular repair following diabetic injury and the underlying mechanism remain unclear.
Methods
Recombinant lentiviral vectors were constructed to target the upregulation or downregulation of DOT1L expression. Carotid artery balloon injury (BI) model was established in diabetic rats. In vitro experiments, an insulin (INS)-stimulated vascular smooth muscle cell (VSMC) model was used. Inflammatory factor levels, vascular intimal hyperplasia and hemodynamics, H3K79me enrichment in promoter regions were detected. ChIP-Seq was used to evaluate the distribution of proteins and genes, and the levels of proteins implicated in related pathways were analyzed.
Results
We found that both in diabetic rat carotid artery tissues 28 days post-BI and in VSMCs after 12 h of insulin stimulation, DOT1L, H3K79me1, IL-6 and TNF-α levels were markedly increased. Overexpression of DOT1L enhanced the expression and release of IL-6 and TNF-α in insulin-induced VSMCs, increased the enrichment of H3K79me1 at the Acp5 gene promoter by 3.92-fold, promoted ACP5 expression, inhibited β-catenin phosphorylation, and upregulated NLRP3 levels. Conversely, downregulation of DOT1L had the opposite effects. In arteries overexpressing DOT1L, inflammatory factor expression and release were markedly enhanced, accompanied by triggering of the ACP5/β-catenin/NLRP3 signaling pathway, roughened intimal surfaces, reduced lumen diameters, decreased residual blood flow area, and increased diameter stenosis rate; greater intimal thickness, and a higher intima/media ratio. In contrast, downregulation of DOT1L exhibited opposite effects.
Conclusion
DOT1L aggravates the inflammatory response following diabetic vascular injury by transcriptionally activating Acp5 through H3K79me1, inhibiting β-catenin phosphorylation and inactivation, and upregulating NLRP3 expression.
{"title":"DOT1L-mediated H3K79me1 transcriptional activation of Acp5 aggravates inflammatory responses following diabetic vascular injury","authors":"Jing Zhang , Zishu Yang , Li Liu , Di Wu , Chen Cheng , Peng Zhu , Wei Wang , Wenqiang Li , Hua Deng , Yudiyang Ma , Cuiyuan Huang , Jian Yang","doi":"10.1016/j.mvr.2025.104882","DOIUrl":"10.1016/j.mvr.2025.104882","url":null,"abstract":"<div><h3>Background</h3><div>Hyperinsulinemia-induced inflammatory responses are a key pathological basis for diabetic proliferative vascular lesions. However, DOT1L impact on vascular repair following diabetic injury and the underlying mechanism remain unclear.</div></div><div><h3>Methods</h3><div>Recombinant lentiviral vectors were constructed to target the upregulation or downregulation of DOT1L expression. Carotid artery balloon injury (BI) model was established in diabetic rats. In vitro experiments, an insulin (INS)-stimulated vascular smooth muscle cell (VSMC) model was used. Inflammatory factor levels, vascular intimal hyperplasia and hemodynamics, H3K79me enrichment in promoter regions were detected. ChIP-Seq was used to evaluate the distribution of proteins and genes, and the levels of proteins implicated in related pathways were analyzed.</div></div><div><h3>Results</h3><div>We found that both in diabetic rat carotid artery tissues 28 days post-BI and in VSMCs after 12 h of insulin stimulation, DOT1L, H3K79me1, IL-6 and TNF-α levels were markedly increased. Overexpression of DOT1L enhanced the expression and release of IL-6 and TNF-α in insulin-induced VSMCs, increased the enrichment of H3K79me1 at the Acp5 gene promoter by 3.92-fold, promoted ACP5 expression, inhibited β-catenin phosphorylation, and upregulated NLRP3 levels. Conversely, downregulation of DOT1L had the opposite effects. In arteries overexpressing DOT1L, inflammatory factor expression and release were markedly enhanced, accompanied by triggering of the ACP5/β-catenin/NLRP3 signaling pathway, roughened intimal surfaces, reduced lumen diameters, decreased residual blood flow area, and increased diameter stenosis rate; greater intimal thickness, and a higher intima/media ratio. In contrast, downregulation of DOT1L exhibited opposite effects.</div></div><div><h3>Conclusion</h3><div>DOT1L aggravates the inflammatory response following diabetic vascular injury by transcriptionally activating Acp5 through H3K79me1, inhibiting β-catenin phosphorylation and inactivation, and upregulating NLRP3 expression.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104882"},"PeriodicalIF":2.7,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145445309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-08-06DOI: 10.1016/j.mvr.2025.104856
Hugang Jiang, Rui Wang, Ai Liu, Jiakun Liu, Xiaying Wang, Wenyan Lin, Chunzhen Ren, Kai Liu, Xinke Zhao, Yingdong Li
Background: Coronary microvascular dysfunction (CMVD) significantly impairs cardiac function and worsens prognosis in patients with cardiovascular diseases, yet no definitively effective pharmacological treatment currently exists. Endothelial cell injury stands as the core pathogenic mechanism of CMVD, however, the molecular mechanisms underlying X-ray radiation-induced endothelial damage remain poorly understood. Although our research group has previously demonstrated that RAS-RH possesses pro-angiogenic properties, its therapeutic potential and mechanistic basis in treating CMVD remain unexplored. Aim This study aims to investigate the potential mechanism by which RAS-RH mitigates radiation-induced coronary microcirculation dysfunction through the inhibition of mitochondrial membrane permeability transition pore (mPTP) opening in endothelial cells.
Methods: We employed a comprehensive set of techniques, including transthoracic echocardiography, coronary microvessel casting technique, carstairs and heidenhain staining, immunohistochemistry, enzyme-linked immunosorbent assay, Western blot, fluorescence in situ hybridization, transmission electron microscopy, TUNEL assay, and flow cytometry, to systematically evaluate cardiac function, coronary vascular structure, myocardial pathological changes, ultrastructural damage, apoptosis, and protein marker expression in an animal model.
Results: In the CMVD rat model, X-ray radiation induced cardiac dysfunction, accompanied by elevated levels of vasoactive substances (TXA₂, ET-1, and vWF) and reduced nitric oxide (NO) production. Coronary vascular injury worsened, evidenced by decreased vascular volume, narrowed lumen diameter, and shortened vessel length. Additionally, capillary density was reduced, myocardial ischemia was exacerbated, and intravascular thrombosis was aggravated. At the molecular level, mPTP-related proteins (CypD, VDAC, F₁F₀-ATPase and ANT) exhibited abnormal expression, while apoptosis-related proteins (Cytc, AIF, caspase-9, and caspase-3) were upregulated, leading to increased apoptotic severity. Ultrastructural damage in cardiomyocytes and telocytes was aggravated, and miR-126 expression was downregulated. These findings suggest that X-ray radiation induces CMVD by triggering excessive mPTP opening in endothelial cells. Notably, interventions with RAS-RH, miR-126 agomir and RAS-RH + miR-126 agomir significantly ameliorated these pathological changes to varying degrees. This demonstrates that RAS-RH mitigates X-ray radiation-induced CMVD by upregulating miR-126 to suppress mPTP overactivation.
Conclusion: RAS-RH effectively ameliorates X-ray radiation-induced CMVD by modulating miR-126 expression to inhibit pathological opening of the mPTP in endothelial cells. This finding provides novel mechanistic evidence supporting RAS-RH as a therapeutic strategy for CMVD.
{"title":"RAS-RH up-regulates the level of miR-126 and inhibits the opening of mPTP in a rat model of coronary microvascular disease.","authors":"Hugang Jiang, Rui Wang, Ai Liu, Jiakun Liu, Xiaying Wang, Wenyan Lin, Chunzhen Ren, Kai Liu, Xinke Zhao, Yingdong Li","doi":"10.1016/j.mvr.2025.104856","DOIUrl":"10.1016/j.mvr.2025.104856","url":null,"abstract":"<p><strong>Background: </strong>Coronary microvascular dysfunction (CMVD) significantly impairs cardiac function and worsens prognosis in patients with cardiovascular diseases, yet no definitively effective pharmacological treatment currently exists. Endothelial cell injury stands as the core pathogenic mechanism of CMVD, however, the molecular mechanisms underlying X-ray radiation-induced endothelial damage remain poorly understood. Although our research group has previously demonstrated that RAS-RH possesses pro-angiogenic properties, its therapeutic potential and mechanistic basis in treating CMVD remain unexplored. Aim This study aims to investigate the potential mechanism by which RAS-RH mitigates radiation-induced coronary microcirculation dysfunction through the inhibition of mitochondrial membrane permeability transition pore (mPTP) opening in endothelial cells.</p><p><strong>Methods: </strong>We employed a comprehensive set of techniques, including transthoracic echocardiography, coronary microvessel casting technique, carstairs and heidenhain staining, immunohistochemistry, enzyme-linked immunosorbent assay, Western blot, fluorescence in situ hybridization, transmission electron microscopy, TUNEL assay, and flow cytometry, to systematically evaluate cardiac function, coronary vascular structure, myocardial pathological changes, ultrastructural damage, apoptosis, and protein marker expression in an animal model.</p><p><strong>Results: </strong>In the CMVD rat model, X-ray radiation induced cardiac dysfunction, accompanied by elevated levels of vasoactive substances (TXA₂, ET-1, and vWF) and reduced nitric oxide (NO) production. Coronary vascular injury worsened, evidenced by decreased vascular volume, narrowed lumen diameter, and shortened vessel length. Additionally, capillary density was reduced, myocardial ischemia was exacerbated, and intravascular thrombosis was aggravated. At the molecular level, mPTP-related proteins (CypD, VDAC, F₁F₀-ATPase and ANT) exhibited abnormal expression, while apoptosis-related proteins (Cytc, AIF, caspase-9, and caspase-3) were upregulated, leading to increased apoptotic severity. Ultrastructural damage in cardiomyocytes and telocytes was aggravated, and miR-126 expression was downregulated. These findings suggest that X-ray radiation induces CMVD by triggering excessive mPTP opening in endothelial cells. Notably, interventions with RAS-RH, miR-126 agomir and RAS-RH + miR-126 agomir significantly ameliorated these pathological changes to varying degrees. This demonstrates that RAS-RH mitigates X-ray radiation-induced CMVD by upregulating miR-126 to suppress mPTP overactivation.</p><p><strong>Conclusion: </strong>RAS-RH effectively ameliorates X-ray radiation-induced CMVD by modulating miR-126 expression to inhibit pathological opening of the mPTP in endothelial cells. This finding provides novel mechanistic evidence supporting RAS-RH as a therapeutic strategy for CMVD.</p>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":" ","pages":"104856"},"PeriodicalIF":2.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diabetic retinopathy (DR) is a leading cause of vision loss in type 2 diabetes mellitus (T2DM), highlighting the need for accessible, non-invasive screening tools. Nail-fold capillaroscopy (NFC) allows in vivo evaluation of microvascular architecture and may provide early markers of DR.
Methods
In this case-control study, 150 T2DM patients (aged 35–75 years) were stratified into DR (n = 75) and non-DR (n = 75) groups. Exclusion criteria included smoking, Raynaud's phenomenon, and ophthalmic comorbidities. NFC images were captured at 200× magnification and analyzed by a blinded rheumatologist. Capillary abnormalities (density, tortuosity, ectasia, crossed-over, bushy, giant capillaries, microhemorrhages, thrombosis) were assessed using validated criteria. Statistical analyses included t-tests, Mann-Whitney U, chi-square, and logistic regression (p < 0.05).
Results
DR patients exhibited significantly higher frequencies of ectatic (p = 0.004), tortuous (p < 0.001), and crossed-over capillaries (p = 0.022) compared to non-DR subjects. Crossed-over vessels were uniquely associated with proliferative DR (p = 0.017), while bushy capillaries were more prevalent in advanced stages (p = 0.021). Sensitivity and specificity for these markers varied, with crossed-over vessels demonstrating 40 % sensitivity and 77.3 % specificity. Capillary tortuosity and ectasia correlated with diabetes duration, whereas crossed-over and bushy vessels were linked to higher BMI.
Conclusions
Nail-fold capillaroscopy reveals distinct microvascular patterns associated with DR and offers a rapid, non-invasive adjunctive screening tool. Crossed-over vessels and tortuosity emerge as practical biomarkers for early risk stratification, particularly in resource-limited settings. Integration with clinical parameters may enhance diagnostic accuracy, supporting timely intervention and prevention of vision loss in high-risk diabetic populations.
{"title":"Nailfold capillaroscopy for early detection of diabetic retinopathy: A non-invasive window into microvascular abnormalities","authors":"Fatemeh Azimian Zavareh , Hamid Reza Bashiri , Mohammad Sadegh Dehghani Firouzabadi , Mohammadreza Gholami Banadkoki , Seyed Mohammad Mohammadi , Azam Ghanei","doi":"10.1016/j.mvr.2025.104881","DOIUrl":"10.1016/j.mvr.2025.104881","url":null,"abstract":"<div><h3>Aims</h3><div>Diabetic retinopathy (DR) is a leading cause of vision loss in type 2 diabetes mellitus (T2DM), highlighting the need for accessible, non-invasive screening tools. Nail-fold capillaroscopy (NFC) allows in vivo evaluation of microvascular architecture and may provide early markers of DR.</div></div><div><h3>Methods</h3><div>In this case-control study, 150 T2DM patients (aged 35–75 years) were stratified into DR (<em>n</em> = 75) and non-DR (n = 75) groups. Exclusion criteria included smoking, Raynaud's phenomenon, and ophthalmic comorbidities. NFC images were captured at 200× magnification and analyzed by a blinded rheumatologist. Capillary abnormalities (density, tortuosity, ectasia, crossed-over, bushy, giant capillaries, microhemorrhages, thrombosis) were assessed using validated criteria. Statistical analyses included <em>t</em>-tests, Mann-Whitney U, chi-square, and logistic regression (<em>p</em> < 0.05).</div></div><div><h3>Results</h3><div>DR patients exhibited significantly higher frequencies of ectatic (<em>p</em> = 0.004), tortuous (<em>p</em> < 0.001), and crossed-over capillaries (<em>p</em> = 0.022) compared to non-DR subjects. Crossed-over vessels were uniquely associated with proliferative DR (<em>p</em> = 0.017), while bushy capillaries were more prevalent in advanced stages (<em>p</em> = 0.021). Sensitivity and specificity for these markers varied, with crossed-over vessels demonstrating 40 % sensitivity and 77.3 % specificity. Capillary tortuosity and ectasia correlated with diabetes duration, whereas crossed-over and bushy vessels were linked to higher BMI.</div></div><div><h3>Conclusions</h3><div>Nail-fold capillaroscopy reveals distinct microvascular patterns associated with DR and offers a rapid, non-invasive adjunctive screening tool. Crossed-over vessels and tortuosity emerge as practical biomarkers for early risk stratification, particularly in resource-limited settings. Integration with clinical parameters may enhance diagnostic accuracy, supporting timely intervention and prevention of vision loss in high-risk diabetic populations.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104881"},"PeriodicalIF":2.7,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-20DOI: 10.1016/j.mvr.2025.104880
Pei-Hsuan Chen , Samar Abood , Steven Bloom
Glucagon-Like Peptide-1 (GLP-1) receptor agonists are widely used to manage type 2 diabetes and promote weight loss. Semaglutide (SEM)—a long acting GLP-1—has experienced an extraordinary surge in popularity since its approval in 2017. Between 2021 and 2023, SEM prescription fills in the U.S. climbed to 2.56 million per month. Yet, the uptake of SEM into larger populations has raised safety concerns, with provocative findings now suggesting that SEM could negatively affect ocular and reproductive systems, counter to its beneficial effects on the heart. At least some of these concerns involve SEMs ability to alter vascular morphology in these organs. Herein, we study the impact of SEM on vasculature using the well-established chicken chorioallantoic membrane (CAM). This in vivo model mimics vascular beds found in the human eye and placenta and can approximate the effects of drugs on these organs. The CAM also responds to vasoactive drugs in a similar way to the coronary arteries of the heart. Hence, the CAM provides a convenient system to simultaneously interrogate the impact of SEM on ocular, reproductive, and coronary vascular biology. Our studies show that SEM causes vessels to develop with fewer branching points, yielding longer and more direct connections, that shift local blow flow patterns. However, these changes are only significant at SEM concentrations well above the therapeutic dose.
{"title":"Effects of semaglutide on vessel morphology: Studies on the chicken chorioallantoic membrane","authors":"Pei-Hsuan Chen , Samar Abood , Steven Bloom","doi":"10.1016/j.mvr.2025.104880","DOIUrl":"10.1016/j.mvr.2025.104880","url":null,"abstract":"<div><div>Glucagon-Like Peptide-1 (GLP-1) receptor agonists are widely used to manage type 2 diabetes and promote weight loss. Semaglutide (SEM)—a long acting GLP-1—has experienced an extraordinary surge in popularity since its approval in 2017. Between 2021 and 2023, SEM prescription fills in the U.S. climbed to 2.56 million <em>per</em> month. Yet, the uptake of SEM into larger populations has raised safety concerns, with provocative findings now suggesting that SEM could negatively affect ocular and reproductive systems, counter to its beneficial effects on the heart. At least some of these concerns involve SEMs ability to alter vascular morphology in these organs. Herein, we study the impact of SEM on vasculature using the well-established chicken chorioallantoic membrane (CAM). This <em>in vivo</em> model mimics vascular beds found in the human eye and placenta and can approximate the effects of drugs on these organs. The CAM also responds to vasoactive drugs in a similar way to the coronary arteries of the heart. Hence, the CAM provides a convenient system to simultaneously interrogate the impact of SEM on ocular, reproductive, and coronary vascular biology. Our studies show that SEM causes vessels to develop with fewer branching points, yielding longer and more direct connections, that shift local blow flow patterns. However, these changes are <em>only</em> significant at SEM concentrations well above the therapeutic dose.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104880"},"PeriodicalIF":2.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145346076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-17DOI: 10.1016/j.mvr.2025.104879
Alice Benedetti , Tijs Bringmans , Maarten Vanhaverbeke , Frédéric Daniel Mathieu , Pieter-Jan Palmers , Patrick Coussement , Kenneth De Wilder , Bert Everaert , Mathieu Coeman , Fabian Demeure , Maarten Kersemans , Peter Kayaert , Jean-François Argacha , Vincent F.M. Segers , Carlo Zivelonghi
Background
Diabetes mellitus (DM) has been associated with coronary microvascular dysfunction (CMD) in previous non-invasive studies. However, invasive studies have shown conflicting results.
Methods
To evaluate the prevalence and predictors of CMD in diabetic patients, invasive coronary physiology data of patients with fractional flow reserve (FFR) > 0.80 on the target vessel were analyzed from the BELmicro registry. Coronary flow reserve (CFR) < 2.5 and index of microcirculatory resistance (IMR) ≥ 25 were considered abnormal.
Results
Out of 402 patients, 72 had DM. Diabetic patients were older [69(61, 75) vs 64(58, 73), p = 0.02] and had higher rates of hypertension (73 % vs 56 %, p = 0.009) and dyslipidemia (89 % vs 64 %, p < 0.001) compared to non-diabetics. No differences were found between diabetic and non-diabetic patients in FFR [0.92(0.89, 0.94) vs 0.91(0.88, 0.94), p = 0.8] and CFR [3.0(2.1, 4.4) vs 2.8(2.0, 4.1), p = 0.4]. IMR was slightly lower in diabetics [16(9, 24) vs 18(12, 27), p = 0.04], but the rate of abnormal IMR was comparable to non-diabetics (23 % vs 31 %, p = 0.2). Prevalence of CMD was similar between diabetics and non-diabetics (46 % vs 48 %, p = 0.8). Rates of CMD were comparable between patients with longstanding DM (≥10 years) and recent diagnosis (52 % vs 35 %, p = 0.2). No association was found between glycated hemoglobin levels and CFR and IMR. Female sex was the only independent predictor of CMD in diabetics (OR: 2.71, 95 % CI: 1.02, 7.50, p = 0.049).
Conclusions
No differences in prevalence of CMD were found between diabetic and non-diabetic patients. Longstanding diabetes, glycemic control and concomitant cardiovascular risk factors were not associated with CMD in diabetic patients.
背景：在以往的非侵入性研究中，糖尿病（DM）与冠状动脉微血管功能障碍（CMD）有关。然而，侵入性研究显示出相互矛盾的结果。方法：为了评估糖尿病患者CMD的患病率及其预测因素，分析BELmicro注册表中靶血管血流储备分数（FFR） > 0.80患者的有创冠状动脉生理学数据。冠状动脉流量储备(CFR) 结果:402名患者,72糖尿病患者老年DM。[69(61、75)和64 (73),p = 0.02],有较高的高血压(73 % vs 56 % p = 0.009)和血脂异常(89 % vs 64 % p 结论:没有发现CMD患病率的差异之间的糖尿病患者和非糖尿病患者。长期糖尿病、血糖控制及伴随的心血管危险因素与糖尿病患者的CMD无关。
{"title":"Invasive coronary physiology assessment and predictors of coronary microvascular dysfunction in patients with diabetes mellitus","authors":"Alice Benedetti , Tijs Bringmans , Maarten Vanhaverbeke , Frédéric Daniel Mathieu , Pieter-Jan Palmers , Patrick Coussement , Kenneth De Wilder , Bert Everaert , Mathieu Coeman , Fabian Demeure , Maarten Kersemans , Peter Kayaert , Jean-François Argacha , Vincent F.M. Segers , Carlo Zivelonghi","doi":"10.1016/j.mvr.2025.104879","DOIUrl":"10.1016/j.mvr.2025.104879","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus (DM) has been associated with coronary microvascular dysfunction (CMD) in previous non-invasive studies. However, invasive studies have shown conflicting results.</div></div><div><h3>Methods</h3><div>To evaluate the prevalence and predictors of CMD in diabetic patients, invasive coronary physiology data of patients with fractional flow reserve (FFR) > 0.80 on the target vessel were analyzed from the BELmicro registry. Coronary flow reserve (CFR) < 2.5 and index of microcirculatory resistance (IMR) ≥ 25 were considered abnormal.</div></div><div><h3>Results</h3><div>Out of 402 patients, 72 had DM. Diabetic patients were older [69(61, 75) vs 64(58, 73), p = 0.02] and had higher rates of hypertension (73 % vs 56 %, p = 0.009) and dyslipidemia (89 % vs 64 %, p < 0.001) compared to non-diabetics. No differences were found between diabetic and non-diabetic patients in FFR [0.92(0.89, 0.94) vs 0.91(0.88, 0.94), p = 0.8] and CFR [3.0(2.1, 4.4) vs 2.8(2.0, 4.1), p = 0.4]. IMR was slightly lower in diabetics [16(9, 24) vs 18(12, 27), p = 0.04], but the rate of abnormal IMR was comparable to non-diabetics (23 % vs 31 %, p = 0.2). Prevalence of CMD was similar between diabetics and non-diabetics (46 % vs 48 %, p = 0.8). Rates of CMD were comparable between patients with longstanding DM (≥10 years) and recent diagnosis (52 % vs 35 %, p = 0.2). No association was found between glycated hemoglobin levels and CFR and IMR. Female sex was the only independent predictor of CMD in diabetics (OR: 2.71, 95 % CI: 1.02, 7.50, p = 0.049).</div></div><div><h3>Conclusions</h3><div>No differences in prevalence of CMD were found between diabetic and non-diabetic patients. Longstanding diabetes, glycemic control and concomitant cardiovascular risk factors were not associated with CMD in diabetic patients.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104879"},"PeriodicalIF":2.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-17DOI: 10.1016/j.mvr.2025.104878
Basmah Safdar , Bin Zhou , Fangyong Li , Paolo G. Camici , James Dziura , Ania M. Jastreboff , Alexandra Lansky , Samit M. Shah , Albert Sinusas , Erica Spatz , Gail D'Onofrio
Objective
To investigate the long-term prognosis of coronary microvascular dysfunction (CMD) in emergency department (ED) patients with chest pain for major adverse cardiac events (MACE) due to all-cause mortality, myocardial infarction (MI), heart failure (HF), or stroke.
Methods
A prospective cohort of ED patients evaluated by hybrid cardiac positron emission tomography with attenuation computed tomography within 24 h of arrival. Patients were classified as: (1) Controls – coronary flow reserve (CFR) ≥2 without perfusion defect or coronary calcification; (2) CMD: CFR <2 without defect or calcification; or (3) CAD/CALC – established or new coronary artery disease (CAD) or calcification (CALC). We conducted annual follow-ups for MACE and all-cause healthcare utilization (hospitalizations and ED visits). We adjusted incidence rates (aIR) and hazard ratio (aHR) for demographics, comorbidities, and medications.
Results
Between 2014 and 2020, 189 patients were enrolled: 95 (50 %) Controls, 34 (18 %) with CMD, and 60 (32 %) with CAD/CALC. Median follow-up time was 50 months (38–92), and a total of 187 unique MACE were recorded in 44 patients. CMD patients had 4× higher MACE risk than controls (aIR 3.8; 95 % CI: 2.1–6.6). CAD/CALC patients had similarly higher risk than controls (aIR: 4.5; 95 % CI: 2.6–7.8). CMD patients had 4× higher risk for time to first MACE than controls (aHR: 3.6; 95 % CI: 1.2–10.7) and higher healthcare utilization per 100 person-months (aIR: 124; 95 % CI: 119–130). Using Seattle Angina Questionnaire, CMD patients showed worse angina frequency than controls (difference: -16.4, 95 % CI: −29.5 to −3.4).
Conclusions
Patients with contemporary phenotypes of ischemia (CMD and CAD/CALC) had higher adverse events than controls, positing ED encounters as an opportunity for early identification and treatment.
{"title":"Clinical profile and long-term outcomes of chest pain patients with coronary microvascular dysfunction from the emergency department – results from the Yale-CMD registry","authors":"Basmah Safdar , Bin Zhou , Fangyong Li , Paolo G. Camici , James Dziura , Ania M. Jastreboff , Alexandra Lansky , Samit M. Shah , Albert Sinusas , Erica Spatz , Gail D'Onofrio","doi":"10.1016/j.mvr.2025.104878","DOIUrl":"10.1016/j.mvr.2025.104878","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the long-term prognosis of coronary microvascular dysfunction (CMD) in emergency department (ED) patients with chest pain for major adverse cardiac events (MACE) due to all-cause mortality, myocardial infarction (MI), heart failure (HF), or stroke.</div></div><div><h3>Methods</h3><div>A prospective cohort of ED patients evaluated by hybrid cardiac positron emission tomography with attenuation computed tomography within 24 h of arrival. Patients were classified as: (1) Controls – coronary flow reserve (CFR) ≥2 without perfusion defect or coronary calcification; (2) CMD: CFR <2 without defect or calcification; or (3) CAD/CALC – established or new coronary artery disease (CAD) or calcification (CALC). We conducted annual follow-ups for MACE and all-cause healthcare utilization (hospitalizations and ED visits). We adjusted incidence rates (aIR) and hazard ratio (aHR) for demographics, comorbidities, and medications.</div></div><div><h3>Results</h3><div>Between 2014 and 2020, 189 patients were enrolled: 95 (50 %) Controls, 34 (18 %) with CMD, and 60 (32 %) with CAD/CALC. Median follow-up time was 50 months (38–92), and a total of 187 unique MACE were recorded in 44 patients. CMD patients had 4× higher MACE risk than controls (aIR 3.8; 95 % CI: 2.1–6.6). CAD/CALC patients had similarly higher risk than controls (aIR: 4.5; 95 % CI: 2.6–7.8). CMD patients had 4× higher risk for time to first MACE than controls (aHR: 3.6; 95 % CI: 1.2–10.7) and higher healthcare utilization per 100 person-months (aIR: 124; 95 % CI: 119–130). Using Seattle Angina Questionnaire, CMD patients showed worse angina frequency than controls (difference: -16.4, 95 % CI: −29.5 to −3.4).</div></div><div><h3>Conclusions</h3><div>Patients with contemporary phenotypes of ischemia (CMD and CAD/CALC) had higher adverse events than controls, positing ED encounters as an opportunity for early identification and treatment.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104878"},"PeriodicalIF":2.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号