Pub Date : 2024-04-24DOI: 10.1097/fjc.0000000000001579
Olivia M. O’Brien, S. Tremble, Ari Kropf, M. Cipolla
Thrombin is a coagulation factor increased in pregnancy and further increased in preeclampsia (PE), a hypertensive disorder. Thrombin is also expressed in brain and may have a nonhemostatic role. We characterized thrombin expression and vasoactivity in brain cerebral parenchymal arterioles (PAs) in rat models of pregnancy and PE. PAs were isolated and pressurized from nonpregnant (NP), late-pregnant (LP) rats and rats with experimental preeclampsia (ePE). Reactivity to thrombin (1-50 U/mL) was measured in the absence and presence of inhibition of cyclooxygenase (COX) and nitric oxide synthase (NOS). Plasma levels of prothrombin, thrombin-antithrombin (TAT), tissue plasminogen activator, and plasminogen activator inhibitor-1 (PAI-1) and cerebrospinal fluid (CSF) levels of TAT were compared via ELISA. Expression of protease-activated receptor (PAR) types 1 and 2 in PAs were measured by Western blot and immunohistochemistry. Neuronal thrombin expression was quantified in brains from all groups by immunohistochemistry. Prothrombin and TAT were elevated in ePE plasma compared to NP and LP. TAT was detected in CSF from all groups and significantly elevated in LP (NP: 0.137±0.014 ng/mL, LP: 0.241±0.015 ng/mL, ePE: 0.192±0.028 ng/mL; p<0.05). Thrombin caused modest vasoconstriction in PAs from all groups regardless of COX or NOS inhibition. PAR1 and PAR2 were found in PAs from all groups co-localized to smooth muscle. Thrombin expression in central neurons was decreased in both LP and ePE groups compared to NP. These findings suggest a role for thrombin and other hemostatic changes during pregnancy and PE beyond coagulation.
凝血酶是一种凝血因子，在妊娠期会增加，在子痫前期（PE）这种高血压疾病中会进一步增加。凝血酶在大脑中也有表达，可能具有非止血作用。我们研究了妊娠和子痫前期大鼠脑实质动脉（PA）中凝血酶的表达和血管活性。我们从非妊娠（NP）大鼠、妊娠晚期（LP）大鼠和实验性子痫前期（ePE）大鼠身上分离并加压了脑实质动脉（PA）。在没有或有环氧化酶（COX）和一氧化氮合酶（NOS）抑制剂的情况下，测量了凝血酶（1-50 U/mL）的反应性。通过 ELISA 比较了血浆中凝血酶原、凝血酶-抗凝血酶（TAT）、组织纤溶酶原激活剂和纤溶酶原激活剂抑制剂-1（PAI-1）的水平以及脑脊液（CSF）中 TAT 的水平。蛋白酶活化受体（PAR）1型和2型在PA中的表达通过Western印迹和免疫组化进行了测定。免疫组化法对各组大脑中神经元凝血酶的表达进行了量化。与NP和LP相比，ePE血浆中凝血酶原和TAT升高。在所有组别的脑脊液中均检测到 TAT，LP 组显著升高（NP：0.137±0.014 ng/mL，LP：0.241±0.014 ng/mL）：0.241±0.015纳克/毫升，ePE：0.192±0.028纳克/毫升；p<0.05）。无论是否抑制 COX 或 NOS，凝血酶都会引起所有组 PA 的适度血管收缩。在所有组的 PA 中发现 PAR1 和 PAR2 与平滑肌共定位。与 NP 相比，LP 组和 ePE 组中枢神经元的凝血酶表达均有所下降。这些研究结果表明，凝血酶和其他止血变化在妊娠和 PE 期间的作用超出了凝血作用。
{"title":"Thrombin in Pregnancy and Preeclampsia: Expression, Localization and Vasoactivity in Brain and Microvessels from Rats","authors":"Olivia M. O’Brien, S. Tremble, Ari Kropf, M. Cipolla","doi":"10.1097/fjc.0000000000001579","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001579","url":null,"abstract":"Thrombin is a coagulation factor increased in pregnancy and further increased in preeclampsia (PE), a hypertensive disorder. Thrombin is also expressed in brain and may have a nonhemostatic role. We characterized thrombin expression and vasoactivity in brain cerebral parenchymal arterioles (PAs) in rat models of pregnancy and PE. PAs were isolated and pressurized from nonpregnant (NP), late-pregnant (LP) rats and rats with experimental preeclampsia (ePE). Reactivity to thrombin (1-50 U/mL) was measured in the absence and presence of inhibition of cyclooxygenase (COX) and nitric oxide synthase (NOS). Plasma levels of prothrombin, thrombin-antithrombin (TAT), tissue plasminogen activator, and plasminogen activator inhibitor-1 (PAI-1) and cerebrospinal fluid (CSF) levels of TAT were compared via ELISA. Expression of protease-activated receptor (PAR) types 1 and 2 in PAs were measured by Western blot and immunohistochemistry. Neuronal thrombin expression was quantified in brains from all groups by immunohistochemistry. Prothrombin and TAT were elevated in ePE plasma compared to NP and LP. TAT was detected in CSF from all groups and significantly elevated in LP (NP: 0.137±0.014 ng/mL, LP: 0.241±0.015 ng/mL, ePE: 0.192±0.028 ng/mL; p<0.05). Thrombin caused modest vasoconstriction in PAs from all groups regardless of COX or NOS inhibition. PAR1 and PAR2 were found in PAs from all groups co-localized to smooth muscle. Thrombin expression in central neurons was decreased in both LP and ePE groups compared to NP. These findings suggest a role for thrombin and other hemostatic changes during pregnancy and PE beyond coagulation.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140660177","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 : 2024-04-24DOI: 10.1097/fjc.0000000000001581
Yana Kakzanov, Ziv Sevilya, Alexander Goldman, Michal Cipok, Vera Hershkovitz, Gabriel Bryk, Eli I. Lev
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been shown to reduce the risk of cardiovascular mortality and hospitalizations in patients with heart failure (HF) with preserved or reduced ejection fraction (HFpEF or HFrEF). The mechanism for this benefit is not clear. Endothelial progenitor cells (EPCs) are bone-marrow derived cells able to differentiate into functional endothelial cells and participate in endothelial repair. The aim of the current study was to evaluate the effect of SGLT-2 inhibitors on the level and function of EPCs in patients with HF. We enrolled 20 patients with symptomatic HF, 12 with HFrEF and 8 with HFpEF (aged 73.3±10.2 years, 95% men). Blood samples were drawn at 2 time points: baseline and ≥3 months after initiation of SGLT-2 inhibitor therapy. Circulating EPC levels were evaluated by expression of VEGFR-2, CD34 and CD133 by flow-cytometry. EPCs colony forming units (CFUs) were quantified after 7 days in culture. The proportion of cells that co-expressed VEGFR-2 and CD34 or VEGFR-2 and CD133 was higher following 3 months of SGLT-2 inhibitors [0.26% (IQR 0.10-0.33) vs. 0.55% (IQR 0.28-0.91), P=0.002; 0.12% (IQR 0.07-0.15) vs. 0.24% (IQR 0.15-0.39), P=0.001, respectively]. EPCs-CFU were also increased following SGLT-2 inhibitor treatment [23 (IQR 3.7-37.8) vs. 79.4 (IQR 25.1-110.25) colonies/106 cells, P=0.0039]. In patients with symptomatic HF, both HFpEF and HFrEF, treatment with SGLT-2 inhibitors is associated with an increase in circulating EPCs level and function. This augmentation in EPCs may be a contributing mechanism to the clinical benefit of SGLT-2 inhibitors in HF patients.
{"title":"The Effect of SGLT2 Inhibitor Therapy on Endothelial Progenitor Cell Function in Patients with Heart Failure","authors":"Yana Kakzanov, Ziv Sevilya, Alexander Goldman, Michal Cipok, Vera Hershkovitz, Gabriel Bryk, Eli I. Lev","doi":"10.1097/fjc.0000000000001581","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001581","url":null,"abstract":"Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been shown to reduce the risk of cardiovascular mortality and hospitalizations in patients with heart failure (HF) with preserved or reduced ejection fraction (HFpEF or HFrEF). The mechanism for this benefit is not clear. Endothelial progenitor cells (EPCs) are bone-marrow derived cells able to differentiate into functional endothelial cells and participate in endothelial repair. The aim of the current study was to evaluate the effect of SGLT-2 inhibitors on the level and function of EPCs in patients with HF. We enrolled 20 patients with symptomatic HF, 12 with HFrEF and 8 with HFpEF (aged 73.3±10.2 years, 95% men). Blood samples were drawn at 2 time points: baseline and ≥3 months after initiation of SGLT-2 inhibitor therapy. Circulating EPC levels were evaluated by expression of VEGFR-2, CD34 and CD133 by flow-cytometry. EPCs colony forming units (CFUs) were quantified after 7 days in culture. The proportion of cells that co-expressed VEGFR-2 and CD34 or VEGFR-2 and CD133 was higher following 3 months of SGLT-2 inhibitors [0.26% (IQR 0.10-0.33) vs. 0.55% (IQR 0.28-0.91), P=0.002; 0.12% (IQR 0.07-0.15) vs. 0.24% (IQR 0.15-0.39), P=0.001, respectively]. EPCs-CFU were also increased following SGLT-2 inhibitor treatment [23 (IQR 3.7-37.8) vs. 79.4 (IQR 25.1-110.25) colonies/106 cells, P=0.0039]. In patients with symptomatic HF, both HFpEF and HFrEF, treatment with SGLT-2 inhibitors is associated with an increase in circulating EPCs level and function. This augmentation in EPCs may be a contributing mechanism to the clinical benefit of SGLT-2 inhibitors in HF patients.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140660877","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 : 2024-04-22DOI: 10.1097/fjc.0000000000001578
Martyna Sikorska, Jakub Chmiel, E. Papuga-Szela, E. Broniatowska, A. Undas
Current guidelines recommend that direct anticoagulants should not be used in prevention of recurrent thrombosis in patients with antiphospholipid syndrome (APS). However, except for triple-positive APS and rivaroxaban use, little evidence supports such recommendation. In a real-life cohort study, we evaluated the risk of thromboembolism and bleeding in APS patients on apixaban versus vitamin K antagonists (VKA). We enrolled 152 APS patients (aged 44 [interquartile range 36-56], 83% women), including 66 patients treated with apixaban 5 mg bid and 86 with warfarin (target INR [international normalized ratio] 2-3). During a median follow-up of 53 months, we recorded venous thromboembolism (VTE), ischemic stroke or myocardial infarction, along with major bleeding. We observed 4 (6.1%, 3 VTE and 1 ischemic stroke) thrombotic events in patients on apixaban and 12 events (14%, 9 VTE, 2 ischemic strokes and 1 myocardial infarction) in VKA patients. APS patients on apixaban had similar risk of recurrent thromboembolism compared to those on warfarin (HR=0.327, 95% CI: 0.104-1.035). Thromboembolic events occurred less commonly in statin users (8% vs 50%, p=0.01) and more frequently in triple-positive APS (50% vs 22.1%, p=0.028) and in subjects with higher D-dimer at baseline (p=0.023); the latter difference was present in the apixaban group (p=0.02). Patients on apixaban had similar risk of major bleeding compared to warfarin (HR=0.54, 95% CI: 0.201-1.448). In real-life APS patients apixaban appears to be similar to VKA for the prevention of thromboembolism and risk of bleeding, which might suggest that some APS patients could be treated with apixaban.
{"title":"Apixaban versus vitamin K antagonists in patients with antiphospholipid syndrome: a cohort study","authors":"Martyna Sikorska, Jakub Chmiel, E. Papuga-Szela, E. Broniatowska, A. Undas","doi":"10.1097/fjc.0000000000001578","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001578","url":null,"abstract":"Current guidelines recommend that direct anticoagulants should not be used in prevention of recurrent thrombosis in patients with antiphospholipid syndrome (APS). However, except for triple-positive APS and rivaroxaban use, little evidence supports such recommendation. In a real-life cohort study, we evaluated the risk of thromboembolism and bleeding in APS patients on apixaban versus vitamin K antagonists (VKA). We enrolled 152 APS patients (aged 44 [interquartile range 36-56], 83% women), including 66 patients treated with apixaban 5 mg bid and 86 with warfarin (target INR [international normalized ratio] 2-3). During a median follow-up of 53 months, we recorded venous thromboembolism (VTE), ischemic stroke or myocardial infarction, along with major bleeding. We observed 4 (6.1%, 3 VTE and 1 ischemic stroke) thrombotic events in patients on apixaban and 12 events (14%, 9 VTE, 2 ischemic strokes and 1 myocardial infarction) in VKA patients. APS patients on apixaban had similar risk of recurrent thromboembolism compared to those on warfarin (HR=0.327, 95% CI: 0.104-1.035). Thromboembolic events occurred less commonly in statin users (8% vs 50%, p=0.01) and more frequently in triple-positive APS (50% vs 22.1%, p=0.028) and in subjects with higher D-dimer at baseline (p=0.023); the latter difference was present in the apixaban group (p=0.02). Patients on apixaban had similar risk of major bleeding compared to warfarin (HR=0.54, 95% CI: 0.201-1.448). In real-life APS patients apixaban appears to be similar to VKA for the prevention of thromboembolism and risk of bleeding, which might suggest that some APS patients could be treated with apixaban.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140677657","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 : 2024-04-22DOI: 10.1097/fjc.0000000000001566
Ye-wei Huang, Fang Luo, Mengmeng Zhang, Li-Tian Wang, WenLuer Meng, Dan-Dan Hu, Jin-Bo Yang, Jun Sheng, Xuanjun Wang
Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein-cholesterol (LDL-C) is the primary goal in preventing and treating AS. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a crucial role in regulating LDL-C metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20(S) protopanaxatriol (20(S)-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20(S)-PPT were investigated in vivo and in vitro by western blotting, real time-polymerase chain reaction (RT-PCR), Enzyme-linked Immunosorbent Assay (ELISA), immunofluorescence staining, and other assays. The in vitro experiments revealed that 20(S)-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low density lipoprotein receptor (LDLR) protein levels, promoted LDL uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of FoxO3 protein and mRNA and decreasing the levels of HNF1α and SREBP2 protein and mRNA. The in vivo experiments revealed that 20(S)-PPT upregulated aortic αSMA expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol fed in ApoE-/- mice (HCF group). Additionally, 20(S)PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the HCF group. The study revealed that 20(S)-PPT inhibited LDLR degradation via PCSK9 to alleviate AS.
{"title":"r20 (S)-protopanaxatriol improves atherosclerosis by inhibiting low-density lipoprotein receptor degradation in ApoE KO mice","authors":"Ye-wei Huang, Fang Luo, Mengmeng Zhang, Li-Tian Wang, WenLuer Meng, Dan-Dan Hu, Jin-Bo Yang, Jun Sheng, Xuanjun Wang","doi":"10.1097/fjc.0000000000001566","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001566","url":null,"abstract":"Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein-cholesterol (LDL-C) is the primary goal in preventing and treating AS. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a crucial role in regulating LDL-C metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20(S) protopanaxatriol (20(S)-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20(S)-PPT were investigated in vivo and in vitro by western blotting, real time-polymerase chain reaction (RT-PCR), Enzyme-linked Immunosorbent Assay (ELISA), immunofluorescence staining, and other assays. The in vitro experiments revealed that 20(S)-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low density lipoprotein receptor (LDLR) protein levels, promoted LDL uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of FoxO3 protein and mRNA and decreasing the levels of HNF1α and SREBP2 protein and mRNA. The in vivo experiments revealed that 20(S)-PPT upregulated aortic αSMA expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol fed in ApoE-/- mice (HCF group). Additionally, 20(S)PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the HCF group. The study revealed that 20(S)-PPT inhibited LDLR degradation via PCSK9 to alleviate AS.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140677982","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}
The study aimed to investigate the pathogenesis of sepsis-induced cardiomyopathy (SIC), a leading cause of mortality in septic patients. Transcriptome data from cecal ligation and puncture (CLP)-induced septic mice were analyzed at different time points (24, 48 and 72 h) using GSE171546 data. Through weighted gene co-expression network analysis (WGCNA), time series, and differential expression analyses, key time-series differentially expressed genes (DEGs) were identified. Additionally, single-cell sequencing data (GSE207363) were used for both differential and pseudotime analyses to pinpoint DEGs specific to endothelial cells. The study highlighted Spock2, S100a9, S100a8, and Xdh as differential genes specific to endothelial cells in a time-dependent manner. Immunofluorescence validation confirmed the increased expression of SPOCK2 in the endothelial cells of CLP-induced septic mice. Further, in vitro studies showed that deletion of Spock2 significantly increased LPS-induced apoptosis in human umbilical vein endothelial cells (HUVECs). In conclusion, SPOCK2 expression is increased in septic cardiac endothelial cells and LPS-induced HUVECs and may play a protective role.
{"title":"Spock2 functions as a key time-series gene of endothelial cells in sepsis-induced cardiomyopathy","authors":"Jian Zhang, Yao Lu, Yihui Shen, Hui Zhang, Yuchen Xu, Xuejun Wang, Yifan Chen, Xiaozhen He, Hao Lu, Leilei Cheng","doi":"10.1097/fjc.0000000000001577","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001577","url":null,"abstract":"The study aimed to investigate the pathogenesis of sepsis-induced cardiomyopathy (SIC), a leading cause of mortality in septic patients. Transcriptome data from cecal ligation and puncture (CLP)-induced septic mice were analyzed at different time points (24, 48 and 72 h) using GSE171546 data. Through weighted gene co-expression network analysis (WGCNA), time series, and differential expression analyses, key time-series differentially expressed genes (DEGs) were identified. Additionally, single-cell sequencing data (GSE207363) were used for both differential and pseudotime analyses to pinpoint DEGs specific to endothelial cells. The study highlighted Spock2, S100a9, S100a8, and Xdh as differential genes specific to endothelial cells in a time-dependent manner. Immunofluorescence validation confirmed the increased expression of SPOCK2 in the endothelial cells of CLP-induced septic mice. Further, in vitro studies showed that deletion of Spock2 significantly increased LPS-induced apoptosis in human umbilical vein endothelial cells (HUVECs). In conclusion, SPOCK2 expression is increased in septic cardiac endothelial cells and LPS-induced HUVECs and may play a protective role.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140676518","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 : 2024-04-10DOI: 10.1097/fjc.0000000000001576
Xuefang Zhang, Gang Sun, Zhiquan Li, Weidong Gao, Wenfeng Tan, Jinxue Liu, Bin Zhang, Juan Wu, Rong Chen, Xiu Juan Li, Gaoxing Zhang
Recent studies have revealed the benefits of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in heart failure patients. However, their effects on acute myocardial infarction (AMI) remain uncertain. Therefore, we conducted this meta-analysis to assess the effectiveness of SGLT2i in patients with AMI with or without diabetes. We conducted a comprehensive search of PubMed, Embase, and Cochrane Library encompassing data from inception until November 30, 2023. Relevant studies comparing SGLT2i with placebo or non-SGLT2i in AMI patients were included. Mean difference (MD) and/or odds ratio (OR) with 95% confidence intervals (CIs) were pooled using a fixed-effects model when the heterogeneity statistic (I2) was less than 50%, otherwise, a random-effects model was employed. Four randomized controlled trials and four observational studies involving 9397 patients with AMI were included in this meta-analysis. Patients treated with SGLT2i exhibited a significantly lower rate of hospitalization for heart failure (HF) (OR=0.50, 95%CI: 0.32-0.80) and all-cause death (OR=0.65, 95%CI: 0.44–0.95) compared to those treated with placebo or non-SGLT2i. Furthermore, the use of SGLT2i was associated with a significant increase in left ventricular ejection fraction (LVEF) (MD=1.90, 95%CI: 1.62-2.17), and a greater reduction of N-terminal pro-hormone of brain natriuretic peptide (OR=0.88, 95%CI 0.82-0.94). Subgroup analysis revealed that in patients with diabetes, SGLT2i exhibited similar effects. The present meta-analysis provided evidence indicating the effectiveness of SGLT2i in patients with AMI, SGLT2i may serve as an additional therapeutic option for AMI patients regardless of the presence or absence of diabetes.
最近的研究表明，钠-葡萄糖共转运体 2 抑制剂（SGLT2i）对心力衰竭患者有好处。然而，它们对急性心肌梗死（AMI）的影响仍不确定。因此，我们进行了这项荟萃分析，以评估 SGLT2i 对伴有或不伴有糖尿病的 AMI 患者的疗效。我们对 PubMed、Embase 和 Cochrane 图书馆进行了全面检索，涵盖了从开始到 2023 年 11 月 30 日的数据。纳入了对 AMI 患者进行 SGLT2i 与安慰剂或非 SGLT2i 比较的相关研究。当异质性统计量（I2）小于50%时，采用固定效应模型对平均差（MD）和/或几率比（OR）及95%置信区间（CI）进行汇总，否则采用随机效应模型。本次荟萃分析共纳入了四项随机对照试验和四项观察性研究，涉及 9397 名 AMI 患者。与使用安慰剂或非SGLT2i治疗的患者相比，使用SGLT2i治疗的患者因心力衰竭（HF）住院（OR=0.50，95%CI：0.32-0.80）和全因死亡（OR=0.65，95%CI：0.44-0.95）的比例明显降低。此外，使用 SGLT2i 与左心室射血分数（LVEF）的显著增加（MD=1.90，95%CI：1.62-2.17）以及脑钠肽 N 端前体的进一步降低（OR=0.88，95%CI 0.82-0.94）有关。亚组分析显示，在糖尿病患者中，SGLT2i 表现出相似的效果。本荟萃分析提供的证据表明，SGLT2i 对急性心肌梗死患者有效，无论是否患有糖尿病，SGLT2i 都可作为急性心肌梗死患者的额外治疗选择。
{"title":"Effectiveness of sodium–glucose cotransporter-2 inhibitors in patients with acute myocardial infarction with or without type 2 diabetes: a systematic review and meta-analysis","authors":"Xuefang Zhang, Gang Sun, Zhiquan Li, Weidong Gao, Wenfeng Tan, Jinxue Liu, Bin Zhang, Juan Wu, Rong Chen, Xiu Juan Li, Gaoxing Zhang","doi":"10.1097/fjc.0000000000001576","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001576","url":null,"abstract":"\u0000 Recent studies have revealed the benefits of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in heart failure patients. However, their effects on acute myocardial infarction (AMI) remain uncertain. Therefore, we conducted this meta-analysis to assess the effectiveness of SGLT2i in patients with AMI with or without diabetes. We conducted a comprehensive search of PubMed, Embase, and Cochrane Library encompassing data from inception until November 30, 2023. Relevant studies comparing SGLT2i with placebo or non-SGLT2i in AMI patients were included. Mean difference (MD) and/or odds ratio (OR) with 95% confidence intervals (CIs) were pooled using a fixed-effects model when the heterogeneity statistic (I2) was less than 50%, otherwise, a random-effects model was employed. Four randomized controlled trials and four observational studies involving 9397 patients with AMI were included in this meta-analysis. Patients treated with SGLT2i exhibited a significantly lower rate of hospitalization for heart failure (HF) (OR=0.50, 95%CI: 0.32-0.80) and all-cause death (OR=0.65, 95%CI: 0.44–0.95) compared to those treated with placebo or non-SGLT2i. Furthermore, the use of SGLT2i was associated with a significant increase in left ventricular ejection fraction (LVEF) (MD=1.90, 95%CI: 1.62-2.17), and a greater reduction of N-terminal pro-hormone of brain natriuretic peptide (OR=0.88, 95%CI 0.82-0.94). Subgroup analysis revealed that in patients with diabetes, SGLT2i exhibited similar effects. The present meta-analysis provided evidence indicating the effectiveness of SGLT2i in patients with AMI, SGLT2i may serve as an additional therapeutic option for AMI patients regardless of the presence or absence of diabetes.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140717064","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}
Hyper-catecholaminergic conditions are known to cause heart failure and cardiac fibrosis when severe. Although previous investigations have studied the effects of beta-blockade in experimental models of catecholaminergic states, the detailed benefits of beta-blockade in more realistic models of hyper-adrenergic states were less clear. In this study, we examined acute cardiac changes in rats with hyper-acute catecholamine-induced heart failure with and without propranolol treatment. Male Sprague-Dawley rats (n = 12) underwent a 6-hour infusion of epinephrine and norepinephrine alone, with an additional propranolol bolus (1 mg/kg) at hour 1 (n=6). Cardiac tissues were examined after 6 hours. Cardiac immunohistochemistry revealed significantly decreased expression of phosphorylated p-38 (LV, p= 0.021; RV, p=0.021), with upregulation of reactive oxidative species and other pro-fibrosis proteins, after catecholamine infusion alone. After one propranolol 1 mg/kg bolus, the levels of phosphorylated-p38 returned to levels comparable to sham (LV, p= 0.021; RV, p= 0.043), with additional findings including downregulation of the apoptotic pathway and pro-fibrotic proteins. We conclude that catecholamine-induced heart failure exerts damage through the p-38 MAP kinase pathway, and demonstrates pro-fibrotic changes mediated by matrix metalloproteinase 9, alpha smooth muscle actin, and fibroblast growth factor-23. Changes in these pathways attenuated acute catecholamine-induced heart failure after propranolol bolus 1 mg/kg. We conclude that propranolol bolus at 1 mg/kg is able to mediate the effects of catecholamine excess through the p-38 MAP kinase pathway, pro-fibrosis, and extrinsic apoptosis pathway.
{"title":"Propranolol Alleviates Cardiac Injury After Acute Catecholamine Infusion via p38-MAPK Pathways","authors":"Tzu-Hao Liu, Rebecca Jen-Ling Hsieh, Hsin-Hung Chen, Tzu-Jiun Kuo, Jui-Chen Lee, Wen-Hsien Lu","doi":"10.1097/fjc.0000000000001571","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001571","url":null,"abstract":"Hyper-catecholaminergic conditions are known to cause heart failure and cardiac fibrosis when severe. Although previous investigations have studied the effects of beta-blockade in experimental models of catecholaminergic states, the detailed benefits of beta-blockade in more realistic models of hyper-adrenergic states were less clear. In this study, we examined acute cardiac changes in rats with hyper-acute catecholamine-induced heart failure with and without propranolol treatment. Male Sprague-Dawley rats (n = 12) underwent a 6-hour infusion of epinephrine and norepinephrine alone, with an additional propranolol bolus (1 mg/kg) at hour 1 (n=6). Cardiac tissues were examined after 6 hours. Cardiac immunohistochemistry revealed significantly decreased expression of phosphorylated p-38 (LV, p= 0.021; RV, p=0.021), with upregulation of reactive oxidative species and other pro-fibrosis proteins, after catecholamine infusion alone. After one propranolol 1 mg/kg bolus, the levels of phosphorylated-p38 returned to levels comparable to sham (LV, p= 0.021; RV, p= 0.043), with additional findings including downregulation of the apoptotic pathway and pro-fibrotic proteins. We conclude that catecholamine-induced heart failure exerts damage through the p-38 MAP kinase pathway, and demonstrates pro-fibrotic changes mediated by matrix metalloproteinase 9, alpha smooth muscle actin, and fibroblast growth factor-23. Changes in these pathways attenuated acute catecholamine-induced heart failure after propranolol bolus 1 mg/kg. We conclude that propranolol bolus at 1 mg/kg is able to mediate the effects of catecholamine excess through the p-38 MAP kinase pathway, pro-fibrosis, and extrinsic apoptosis pathway.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140717370","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 : 2024-04-10DOI: 10.1097/fjc.0000000000001573
Shuai Jiang, Yitong Li, Jiali Zhang, Wenhui Jia, Yizheng Zheng, Zhiping Jia, Chenming Yu, Yi Kong
Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. Here, analyses of activated partial thromboplastin time (aPTT) in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identify synergistic anticoagulation effects. Both an FeCl3-induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery (tMCAO) mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.
{"title":"Dual Inhibition of Factor XIIa and Factor XIa Produces a Synergistic Anticoagulant Effect","authors":"Shuai Jiang, Yitong Li, Jiali Zhang, Wenhui Jia, Yizheng Zheng, Zhiping Jia, Chenming Yu, Yi Kong","doi":"10.1097/fjc.0000000000001573","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001573","url":null,"abstract":"Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. Here, analyses of activated partial thromboplastin time (aPTT) in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identify synergistic anticoagulation effects. Both an FeCl3-induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery (tMCAO) mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140719497","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 : 2024-04-09DOI: 10.1097/fjc.0000000000001575
Hao-wei Deng, Zi-ming Ye, Rui-ting Hu, Chao Qin
Aneurysms are localized dilations of blood vessels, which can expand to 50% of the original diameter. They are more common in cardiovascular and cerebrovascular vessels. Rupture is one of the most dangerous complications. The pathophysiology of aneurysms is complex and diverse, often associated with progressive vessel wall dysfunction resulting from vascular smooth muscle cell (VSMC) death and abnormal extracellular matrix synthesis and degradation. Multiple studies have shown that long non-coding RNAs (lncRNAs) play a significant role in the progression of cardiovascular and cerebrovascular diseases. Therefore, it is necessary to find and summarize them. LncRNAs control gene expression and disease progression by regulating target mRNA or miRNA, and are biomarkers for the diagnosis and prognosis of aneurysmal cardiovascular and cerebrovascular diseases. This review explores the role, mechanism and clinical value of lncRNAs in aneurysms, providing new insights for a deeper understanding of the pathogenesis of cardiovascular and cerebrovascular aneurysms.
{"title":"The Role of Long Non-Coding RNAs in Vascular Smooth Muscle Cell Phenotype and the Pathogenesis of Cardiovascular and Cerebrovascular Aneurysms","authors":"Hao-wei Deng, Zi-ming Ye, Rui-ting Hu, Chao Qin","doi":"10.1097/fjc.0000000000001575","DOIUrl":"https://doi.org/10.1097/fjc.0000000000001575","url":null,"abstract":"Aneurysms are localized dilations of blood vessels, which can expand to 50% of the original diameter. They are more common in cardiovascular and cerebrovascular vessels. Rupture is one of the most dangerous complications. The pathophysiology of aneurysms is complex and diverse, often associated with progressive vessel wall dysfunction resulting from vascular smooth muscle cell (VSMC) death and abnormal extracellular matrix synthesis and degradation. Multiple studies have shown that long non-coding RNAs (lncRNAs) play a significant role in the progression of cardiovascular and cerebrovascular diseases. Therefore, it is necessary to find and summarize them. LncRNAs control gene expression and disease progression by regulating target mRNA or miRNA, and are biomarkers for the diagnosis and prognosis of aneurysmal cardiovascular and cerebrovascular diseases. This review explores the role, mechanism and clinical value of lncRNAs in aneurysms, providing new insights for a deeper understanding of the pathogenesis of cardiovascular and cerebrovascular aneurysms.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140727049","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 : 2024-04-04DOI: 10.1097/FJC.0000000000001574
Nadia L. Martínez Naya, Martin Denicolai, Jazmin Kelly, Stefano Toldo
{"title":"Cannabinoids and Post-Cardiac Surgery: Preclinical Insights Pave the Way for Future Research.","authors":"Nadia L. Martínez Naya, Martin Denicolai, Jazmin Kelly, Stefano Toldo","doi":"10.1097/FJC.0000000000001574","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001574","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140743506","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：