Background: Restenosis (RS) poses a significant concern, leading to recurrent ischemia and the potential for amputation following intraluminal angioplasty in the treatment of Peripheral Artery Disease (PAD). Through microRNA microarray analysis, the study detected a significant downregulation of miR-199a-5p within arterial smooth muscle cells (ASMCs) associated with RS.
Objective: This research aims to explore the possible function and the underlying mechanisms of miR-199a-5p in the context of RS.
Methods: Primary ASMCs were extracted from the femoral arteries of both healthy individuals and patients with PAD or RS. The expression levels of miR-199a-5p were assessed using both qRT-PCR and in situ hybridization techniques. To examine the impacts of miR-199a-5p, a series of experiments were performed, including flow cytometry, TUNEL assay, EdU assay, CCK8 assay, Transwell assay, and wound closure assay. A rat carotid balloon injury model was employed to elucidate the mechanism through which miR-199a-5p mitigated neointimal hyperplasia.
Results: MiR-199a-5p exhibited downregulation in RS patients and was predominantly expressed within ASMCs. Elevated the expression of miR-199a-5p resulted in an inhibitory effect of proliferation and migration in ASMCs. Immunohistochemistry and a dual-luciferase reporter assay uncovered that RS exhibited elevated expression levels of both HIF-1α and E2F3, and they were identified as target genes regulated by miR-199a-5p. The co-transfection of lentiviruses carrying HIF-1α and E2F3 alongside miR-199a-5p further elucidated their role in the cellular responses mediated by miR-199a-5p. In vivo, the delivery of miR-199a-5p via lentivirus led to the mitigation of neointimal formation following angioplasty, achieved by targeting HIF-1α and E2F3.
Conclusion: MiR-199a-5p exhibits promise as a prospective therapeutic target for RS since it alleviates the condition by inhibiting the proliferation and migration of ASMCs via its regulation of HIF-1α and E2F3.
{"title":"MiR-199a-5p Deficiency Promotes Artery Restenosis in Peripheral Artery Disease by Regulating ASMCs Function <i>via</i> Targeting HIF-1α and E2F3.","authors":"Duan Liu, Yexiang Jing, Guiyan Peng, Litai Wei, Liang Zheng, Guangqi Chang, Mian Wang","doi":"10.2174/0115701611280634240616062413","DOIUrl":"10.2174/0115701611280634240616062413","url":null,"abstract":"<p><strong>Background: </strong>Restenosis (RS) poses a significant concern, leading to recurrent ischemia and the potential for amputation following intraluminal angioplasty in the treatment of Peripheral Artery Disease (PAD). Through microRNA microarray analysis, the study detected a significant downregulation of miR-199a-5p within arterial smooth muscle cells (ASMCs) associated with RS.</p><p><strong>Objective: </strong>This research aims to explore the possible function and the underlying mechanisms of miR-199a-5p in the context of RS.</p><p><strong>Methods: </strong>Primary ASMCs were extracted from the femoral arteries of both healthy individuals and patients with PAD or RS. The expression levels of miR-199a-5p were assessed using both qRT-PCR and in situ hybridization techniques. To examine the impacts of miR-199a-5p, a series of experiments were performed, including flow cytometry, TUNEL assay, EdU assay, CCK8 assay, Transwell assay, and wound closure assay. A rat carotid balloon injury model was employed to elucidate the mechanism through which miR-199a-5p mitigated neointimal hyperplasia.</p><p><strong>Results: </strong>MiR-199a-5p exhibited downregulation in RS patients and was predominantly expressed within ASMCs. Elevated the expression of miR-199a-5p resulted in an inhibitory effect of proliferation and migration in ASMCs. Immunohistochemistry and a dual-luciferase reporter assay uncovered that RS exhibited elevated expression levels of both HIF-1α and E2F3, and they were identified as target genes regulated by miR-199a-5p. The co-transfection of lentiviruses carrying HIF-1α and E2F3 alongside miR-199a-5p further elucidated their role in the cellular responses mediated by miR-199a-5p. <i>In vivo</i>, the delivery of miR-199a-5p <i>via</i> lentivirus led to the mitigation of neointimal formation following angioplasty, achieved by targeting HIF-1α and E2F3.</p><p><strong>Conclusion: </strong>MiR-199a-5p exhibits promise as a prospective therapeutic target for RS since it alleviates the condition by inhibiting the proliferation and migration of ASMCs <i>via</i> its regulation of HIF-1α and E2F3.</p>","PeriodicalId":11278,"journal":{"name":"Current vascular pharmacology","volume":" ","pages":"342-354"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-23DOI: 10.2174/0115701611267835231210054909
Debabrata Mukherjee, Steven E Nissen
Background: Lipoprotein (a) [Lp(a)] is a molecule that induces inflammation of the blood vessels, atherogenesis, valvular calcification, and thrombosis. Methods: We review the available evidence that suggests that high Lp(a) levels are associated with a persisting risk for atherosclerotic cardiovascular diseases despite optimization of established risk factors, including low-density lipoprotein cholesterol (LDL-C) levels. Observations: Approximately a quarter of the world population have Lp(a) levels of >50 mg/dL (125 nmol/L), a level associated with elevated cardiovascular risk. Lifestyle modification, statins, and ezetimibe do not effectively lower Lp(a) levels, while proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors and niacin only lower Lp(a) levels modestly. We describe clinical studies suggesting that gene silencing therapeutics, such as small interfering RNA (siRNA) and antisense oligonucleotide targeting Lp(a), offer a targeted approach with the potential for safe and robust Lp(a)- lowering with only a few doses (3-4) per year. Prospective randomized phase 3 studies are ongoing to validate safety, effectiveness in improving hard clinical outcomes, and tolerability to assess these therapies. Conclusion: Several emerging treatments with robust Lp(a)-lowering effects may significantly lower atherosclerotic cardiovascular risk.
{"title":"Lipoprotein (a) as a Biomarker for Cardiovascular Diseases and Potential New Therapies to Mitigate Risk","authors":"Debabrata Mukherjee, Steven E Nissen","doi":"10.2174/0115701611267835231210054909","DOIUrl":"https://doi.org/10.2174/0115701611267835231210054909","url":null,"abstract":"Background: Lipoprotein (a) [Lp(a)] is a molecule that induces inflammation of the blood vessels, atherogenesis, valvular calcification, and thrombosis. Methods: We review the available evidence that suggests that high Lp(a) levels are associated with a persisting risk for atherosclerotic cardiovascular diseases despite optimization of established risk factors, including low-density lipoprotein cholesterol (LDL-C) levels. Observations: Approximately a quarter of the world population have Lp(a) levels of >50 mg/dL (125 nmol/L), a level associated with elevated cardiovascular risk. Lifestyle modification, statins, and ezetimibe do not effectively lower Lp(a) levels, while proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors and niacin only lower Lp(a) levels modestly. We describe clinical studies suggesting that gene silencing therapeutics, such as small interfering RNA (siRNA) and antisense oligonucleotide targeting Lp(a), offer a targeted approach with the potential for safe and robust Lp(a)- lowering with only a few doses (3-4) per year. Prospective randomized phase 3 studies are ongoing to validate safety, effectiveness in improving hard clinical outcomes, and tolerability to assess these therapies. Conclusion: Several emerging treatments with robust Lp(a)-lowering effects may significantly lower atherosclerotic cardiovascular risk.","PeriodicalId":11278,"journal":{"name":"Current vascular pharmacology","volume":"4 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139027628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-23DOI: 10.2174/0115701611269801231211104905
Wei Zuo, Liang Wang, Ran Tian, Lun Wang, Yifan Liu, Hao Qian, Xinglin Yang, Zhenyu Liu
Introduction:: Myocardial ischaemia reperfusion injury (MIRI) determines infarct size and long-term outcomes after acute myocardial infarction (AMI). Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, alleviates MIRI in animal models. Method:: We investigated the potential mechanisms underlying the cardioprotective effect of dapagliflozin against MIRI, focusing on mitochondrial injury and mitophagy. MIRI mouse and H9C2 cell models were established. Results:: 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed a significant alleviation of MIRI after pre-treatment of dapagliflozin compared to the model group (14.91±1.76 vs. 40.47±3.69%). Data from the pre-treatment dapagliflozin group showed a significant decrease in left ventricular ejection fraction (LVEF) (44.8±2.7 vs. 28.5±5.3%, P<0.01), left ventricular end-diastolic volume (LVEDV) (70.6±9.5 vs. 93.5±13.8 ul, P<0.05), and left ventricular end-systolic volume (LVESV) (39.0± 8.3 vs. 67.9±13.7 ul, P<0.05) compared to the model group. Dapagliflozin also reduced the levels of reactive oxygen species (ROS) and fragmented mitochondrial DNA, reversed the decrease in mitochondrial membrane potential, and suppressed apoptosis. Further study showed that dapagliflozin could protect against mitochondrial injury by rapidly clearing damaged mitochondria via mitophagy in a phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1)/parkindependent manner. Dapagliflozin regulated mitophagy in cardiomyocytes by suppressing the adenosine 5’monophosphate-activated protein kinase (AMPK)-PINK1/parkin signalling pathway, resulting in attenuated MIRI. Conclusion:: Dapagliflozin alleviated MIRI by activating mitophagy via the AMPK-PINK1/parkin signalling pathway.
导言心肌缺血再灌注损伤（MIRI）决定了急性心肌梗死（AMI）后的梗死面积和长期预后。钠-葡萄糖共转运体 2 抑制剂达帕格列酮可减轻动物模型中的 MIRI。方法：我们研究了达帕格列净对 MIRI 的心脏保护作用的潜在机制，重点是线粒体损伤和有丝分裂。建立了 MIRI 小鼠和 H9C2 细胞模型。结果2,3,5-三苯基氯化四氮唑（TTC）染色显示，与模型组相比，预处理达帕格列净后 MIRI 明显减轻（14.91±1.76 vs. 40.47±3.69%）。治疗前达帕格列净组的数据显示，左室射血分数（LVEF）显著下降（44.8±2.7 vs. 28.5±5.3%，P<0.01）、左室舒张末期容积（LVEDV）（70.6±9.5 vs. 93.5±13.8 ul，P<0.05）和左室收缩末期容积（LVESV）（39.0±8.3 vs. 67.9±13.7 ul，P<0.05）与模型组相比均显著下降。达帕格列净还降低了活性氧（ROS）和线粒体DNA碎片的水平，逆转了线粒体膜电位的下降，抑制了细胞凋亡。进一步的研究表明，达帕格列净可以保护线粒体免受损伤，因为它可以通过磷酸酶和天丝同源物（PTEN）诱导的假定激酶1（PINK1）/park依赖性方式，通过线粒体吞噬迅速清除受损的线粒体。达帕格列净通过抑制 5'单磷酸腺苷激活的蛋白激酶（AMPK）-PINK1/parkin 信号通路来调节心肌细胞的有丝分裂，从而导致 MIRI 的减弱。结论达帕格列净通过AMPK-PINK1/parkin信号通路激活有丝分裂，从而缓解了MIRI。
{"title":"Dapagliflozin Alleviates Myocardial Ischaemia Reperfusion Injury by Activating Mitophagy via the AMPK-PINK1/Parkin Signalling Pathway","authors":"Wei Zuo, Liang Wang, Ran Tian, Lun Wang, Yifan Liu, Hao Qian, Xinglin Yang, Zhenyu Liu","doi":"10.2174/0115701611269801231211104905","DOIUrl":"https://doi.org/10.2174/0115701611269801231211104905","url":null,"abstract":"Introduction:: Myocardial ischaemia reperfusion injury (MIRI) determines infarct size and long-term outcomes after acute myocardial infarction (AMI). Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, alleviates MIRI in animal models. Method:: We investigated the potential mechanisms underlying the cardioprotective effect of dapagliflozin against MIRI, focusing on mitochondrial injury and mitophagy. MIRI mouse and H9C2 cell models were established. Results:: 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed a significant alleviation of MIRI after pre-treatment of dapagliflozin compared to the model group (14.91±1.76 vs. 40.47±3.69%). Data from the pre-treatment dapagliflozin group showed a significant decrease in left ventricular ejection fraction (LVEF) (44.8±2.7 vs. 28.5±5.3%, P<0.01), left ventricular end-diastolic volume (LVEDV) (70.6±9.5 vs. 93.5±13.8 ul, P<0.05), and left ventricular end-systolic volume (LVESV) (39.0± 8.3 vs. 67.9±13.7 ul, P<0.05) compared to the model group. Dapagliflozin also reduced the levels of reactive oxygen species (ROS) and fragmented mitochondrial DNA, reversed the decrease in mitochondrial membrane potential, and suppressed apoptosis. Further study showed that dapagliflozin could protect against mitochondrial injury by rapidly clearing damaged mitochondria via mitophagy in a phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1)/parkindependent manner. Dapagliflozin regulated mitophagy in cardiomyocytes by suppressing the adenosine 5’monophosphate-activated protein kinase (AMPK)-PINK1/parkin signalling pathway, resulting in attenuated MIRI. Conclusion:: Dapagliflozin alleviated MIRI by activating mitophagy via the AMPK-PINK1/parkin signalling pathway.","PeriodicalId":11278,"journal":{"name":"Current vascular pharmacology","volume":"24 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139027629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-15DOI: 10.2174/0115701611270174231204110557
Goran Koracevic, Milovan Stojanovic, Marija Zdravkovic, Dragan Lovic, Dragan Simic, Katarina Mladenovic
: Systemic arterial hypertension (HTN) is the main cause of morbidity and mortality, and HTN crises contribute significantly to an unfavourable clinical course. For decades, HTN crises have been dichotomized into hypertensive emergency (HTN-E) and hypertensive urgency (HTN-U). The main difference between the two is the presence of acute hypertension-mediated organ damage (HMOD) – if HMOD is present, HTN crisis is HTN-E; if not, it is HTN-U. Patients with HTN-E are in a life-threatening situation. They are hospitalized and receive antihypertensive drugs intravenously (IV). On the other hand, patients with HTN-U are usually not hospitalized and receive their antihypertensives orally. We suggest a modification of the current risk stratification scheme for patients with HTN crises. The new category would be the intermediate risk group, more precisely the ‘impending HTN-E’ group, with a higher risk in comparison to HTN-U and a lower risk than HTN-E. ‘Impending HMOD’ means that HMOD has not occurred (yet), and the prognosis is, therefore, better than in patients with ongoing HMOD. There are three main reasons to classify patients as having impending HTN-E: excessively elevated BP, high-risk comorbidities, and ongoing bleeding/high bleeding risk. Their combinations are probable. This approach may enable us to prevent some HTNEs by avoiding acute HMOD using a timely blood pressure treatment. This treatment should be prompt but controlled.
{"title":"Proposal of a Modified Classification of Hypertensive Crises: Urgency, Impending Emergency, and Emergency","authors":"Goran Koracevic, Milovan Stojanovic, Marija Zdravkovic, Dragan Lovic, Dragan Simic, Katarina Mladenovic","doi":"10.2174/0115701611270174231204110557","DOIUrl":"https://doi.org/10.2174/0115701611270174231204110557","url":null,"abstract":": Systemic arterial hypertension (HTN) is the main cause of morbidity and mortality, and HTN crises contribute significantly to an unfavourable clinical course. For decades, HTN crises have been dichotomized into hypertensive emergency (HTN-E) and hypertensive urgency (HTN-U). The main difference between the two is the presence of acute hypertension-mediated organ damage (HMOD) – if HMOD is present, HTN crisis is HTN-E; if not, it is HTN-U. Patients with HTN-E are in a life-threatening situation. They are hospitalized and receive antihypertensive drugs intravenously (IV). On the other hand, patients with HTN-U are usually not hospitalized and receive their antihypertensives orally. We suggest a modification of the current risk stratification scheme for patients with HTN crises. The new category would be the intermediate risk group, more precisely the ‘impending HTN-E’ group, with a higher risk in comparison to HTN-U and a lower risk than HTN-E. ‘Impending HMOD’ means that HMOD has not occurred (yet), and the prognosis is, therefore, better than in patients with ongoing HMOD. There are three main reasons to classify patients as having impending HTN-E: excessively elevated BP, high-risk comorbidities, and ongoing bleeding/high bleeding risk. Their combinations are probable. This approach may enable us to prevent some HTNEs by avoiding acute HMOD using a timely blood pressure treatment. This treatment should be prompt but controlled.","PeriodicalId":11278,"journal":{"name":"Current vascular pharmacology","volume":"15 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138683515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-11DOI: 10.2174/0115701611233184231206100222
Sabato Sorrentino, Assunta Di Costanzo, Nadia Salerno, Alessandro Caracciolo, Federica Bruno, Alessandra Panarello, Antonio Bellantoni, Annalisa Mongiardo, Ciro Indolfi
: Large bore accesses refer to accesses with a diameter of 10 French or greater and are necessary for various medical devices, including those used in transcatheter aortic valve replacement, endovascular aneurysm repair stent-grafts, and percutaneous mechanical support devices. Notably, the utilization of these devices via femoral access is steadily increasing due to advancements in technology and implantation techniques, which are expanding the pool of patients suitable for percutaneous procedures. However, procedures involving large bore devices carry a high risk of bleeding and vascular complications (VCs), impacting both morbidity and long-term mortality. In this review article, we will first discuss the incidence, determinants, and prognostic impact of VCs in patients undergoing large bore access procedures. Subsequently, we will explore the strategies developed in recent years to minimize VCs, including techniques for optimizing vascular puncture through femoral cannulation, such as the use of echo-guided access cannulation and fluoroscopic guidance. Additionally, we will evaluate existing vascular closure devices designed for large bore devices. Finally, we will consider new pharmacological strategies aimed at reducing the risk of periprocedural access-related bleeding.
:大口径通道是指直径为 10 French 或更大的通道，是各种医疗设备（包括用于经导管主动脉瓣置换术、血管内动脉瘤修复支架移植物和经皮机械支持设备）所必需的。值得注意的是，由于技术和植入技术的进步，经股动脉入路使用这些设备的情况正在稳步增加，这也扩大了适合经皮手术的患者群体。然而，涉及大口径设备的手术具有出血和血管并发症（VC）的高风险，会影响发病率和长期死亡率。在这篇综述文章中，我们将首先讨论大孔径入路手术患者血管并发症的发生率、决定因素和对预后的影响。随后，我们将探讨近年来为最大限度减少 VCs 而开发的策略，包括通过股骨插管优化血管穿刺的技术，如使用回声引导入路插管和透视引导。此外，我们还将评估专为大口径器械设计的现有血管闭合装置。最后，我们还将考虑旨在降低围手术期入路相关出血风险的新药物策略。
{"title":"Strategies to Minimize Access Site-related Complications in Patients Undergoing Transfemoral Artery Procedures with Large-bore Devices","authors":"Sabato Sorrentino, Assunta Di Costanzo, Nadia Salerno, Alessandro Caracciolo, Federica Bruno, Alessandra Panarello, Antonio Bellantoni, Annalisa Mongiardo, Ciro Indolfi","doi":"10.2174/0115701611233184231206100222","DOIUrl":"https://doi.org/10.2174/0115701611233184231206100222","url":null,"abstract":": Large bore accesses refer to accesses with a diameter of 10 French or greater and are necessary for various medical devices, including those used in transcatheter aortic valve replacement, endovascular aneurysm repair stent-grafts, and percutaneous mechanical support devices. Notably, the utilization of these devices via femoral access is steadily increasing due to advancements in technology and implantation techniques, which are expanding the pool of patients suitable for percutaneous procedures. However, procedures involving large bore devices carry a high risk of bleeding and vascular complications (VCs), impacting both morbidity and long-term mortality. In this review article, we will first discuss the incidence, determinants, and prognostic impact of VCs in patients undergoing large bore access procedures. Subsequently, we will explore the strategies developed in recent years to minimize VCs, including techniques for optimizing vascular puncture through femoral cannulation, such as the use of echo-guided access cannulation and fluoroscopic guidance. Additionally, we will evaluate existing vascular closure devices designed for large bore devices. Finally, we will consider new pharmacological strategies aimed at reducing the risk of periprocedural access-related bleeding.","PeriodicalId":11278,"journal":{"name":"Current vascular pharmacology","volume":"19 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138575055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-11DOI: 10.2174/0115701611250248231114114557
Andrea Sartorio, Giulia Burrei, Luca Cristin, Mirko Zoncapè, Michele Carlin, Enrico Tadiello, Pietro Minuz, Andrea Dalbeni, Simone Romano
Background:: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes Coronavirus disease 2019 (COVID-19), characterized by pulmonary infection ranging from asymptomatic forms to respiratory insufficiency and death. Evidence of cardiac involvement in COVID-19 is increasing, and systemic inflammation or direct heart damage by SARS-CoV-2 can prolong the corrected QT interval (QTc). Methods:: In this observational study, a total of 333 consecutive patients admitted to the Covid Center of Verona University Hospital from November 2020 to April 2021 were included. Patients with bundle branch block, pacemaker-controlled heart rhythm and heart rate >120 beats/min were excluded. A complete electrocardiogram (ECG) was performed at admission, and QTc values of ≥440 ms for males and ≥460 ms for females were considered prolonged. Results:: Overall, 153 patients had prolonged QTc (45.5%). In multivariate logistic regression analysis, male sex (odds ratio (OR)=6.612, p=0.046), troponin (OR=1.04, p=0.015) and lymphocyte count (OR=3.047, p=0.019) were independently associated with QTc prolongation. Multivariate logistic regression showed that QTc was independently associated with mortality (OR=4.598, p=0.036). Age, sex, the ratio between the partial pressure of oxygen (PaO2) and the fraction of inspired oxygen (FiO2) (P/F), and fibrosis-4 index for liver fibrosis (FIB-4) were also independently associated with mortality. Conclusion:: QTc interval prolongation appears to be a frequent finding in patients with COVID-19. Moreover, prolonged QTc may be predictive of more severe forms of COVID-19 and worse outcome.
{"title":"QTc Prolongation to Predict Mortality in Patients Admitted with COVID- 19 Infection: An Observational Study","authors":"Andrea Sartorio, Giulia Burrei, Luca Cristin, Mirko Zoncapè, Michele Carlin, Enrico Tadiello, Pietro Minuz, Andrea Dalbeni, Simone Romano","doi":"10.2174/0115701611250248231114114557","DOIUrl":"https://doi.org/10.2174/0115701611250248231114114557","url":null,"abstract":"Background:: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes Coronavirus disease 2019 (COVID-19), characterized by pulmonary infection ranging from asymptomatic forms to respiratory insufficiency and death. Evidence of cardiac involvement in COVID-19 is increasing, and systemic inflammation or direct heart damage by SARS-CoV-2 can prolong the corrected QT interval (QTc). Methods:: In this observational study, a total of 333 consecutive patients admitted to the Covid Center of Verona University Hospital from November 2020 to April 2021 were included. Patients with bundle branch block, pacemaker-controlled heart rhythm and heart rate >120 beats/min were excluded. A complete electrocardiogram (ECG) was performed at admission, and QTc values of ≥440 ms for males and ≥460 ms for females were considered prolonged. Results:: Overall, 153 patients had prolonged QTc (45.5%). In multivariate logistic regression analysis, male sex (odds ratio (OR)=6.612, p=0.046), troponin (OR=1.04, p=0.015) and lymphocyte count (OR=3.047, p=0.019) were independently associated with QTc prolongation. Multivariate logistic regression showed that QTc was independently associated with mortality (OR=4.598, p=0.036). Age, sex, the ratio between the partial pressure of oxygen (PaO2) and the fraction of inspired oxygen (FiO2) (P/F), and fibrosis-4 index for liver fibrosis (FIB-4) were also independently associated with mortality. Conclusion:: QTc interval prolongation appears to be a frequent finding in patients with COVID-19. Moreover, prolonged QTc may be predictive of more severe forms of COVID-19 and worse outcome.","PeriodicalId":11278,"journal":{"name":"Current vascular pharmacology","volume":"60 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138574674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.2174/1570161121666230913093441
Laith Al-Eitan, Mishael Alkhawaldeh
Aim: This study aims to explore the impact of the synthetic cannabinoid methyl 2-(1-(4- fluorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (MDMB-FUBINACA) on the angiogenesis process in human brain microvascular endothelial cells.
Background: Synthetic cannabinoids (SCs) are substances that mimic the natural components found in the cannabis plant. SCs are considered prohibited substances that have a clear impact on the central nervous system (CNS).
Objectives: The purpose of this study is to explore how MDMB-FUBINACA influences angiogenesis in human brain microvascular endothelial cells and to clarify the pathways related to the cannabinoid receptors.
Methods: Human brain microvascular endothelial cells (hBMECs) were grown in the medium containing Dulbecco Modified Eagle Medium (DMEM/F12) using an endothelial cell growth kit. Endothelial cell viability was evaluated using the MTT test. Migration ability was measured using the Wound healing test. The angiogenic capability was measured using a Tube Formation assay. Real-time polymerase chain reaction (RT-PCR) was utilized to explore the mRNA concentrations following MDMBFUBINACA treatment. ELISA and Western blotting were also employed to measure the protein levels.
Results: MDMB-FUBINACA greatly increases tube formation, endothelial cell proliferation, and migration. Pro-angiogenic factors such as angiopoietins 1 and 2 (ANG-1 and 2) and vascular endothelial growth factor (VEGF) were shown to be increased at both the RNA and protein levels.
Conclusion: MDMB-FUBINACA induces the progression of the angiogenesis process by inducing the expression of pro-angiogenic factors. These findings aim toward developing novel treatments for angiogenesis- related disorders.
目的:探讨合成大麻素甲基2-(1-(4-氟苯基)- 1h -吲唑-3-羧胺)-3,3-二甲基丁酸酯(MDMB-FUBINACA)对人脑微血管内皮细胞血管生成过程的影响。背景:合成大麻素(SCs)是模仿大麻植物中发现的天然成分的物质。SCs被认为是对中枢神经系统(CNS)有明显影响的违禁物质。目的:探讨MDMB-FUBINACA对人脑微血管内皮细胞血管生成的影响，并阐明大麻素受体的相关通路。方法:采用内皮细胞生长试剂盒，在含有Dulbecco Modified Eagle medium (DMEM/F12)的培养基中培养人脑微血管内皮细胞(hBMECs)。采用MTT试验评估内皮细胞活力。采用伤口愈合试验测定迁移能力。血管生成能力的测量使用管形成试验。采用实时聚合酶链反应(RT-PCR)检测MDMBFUBINACA处理后的mRNA浓度。ELISA和Western blotting检测蛋白水平。结果:MDMB-FUBINACA可显著促进血管形成、内皮细胞增殖和迁移。促血管生成因子如血管生成素1和2 (ANG-1和2)和血管内皮生长因子(VEGF)在RNA和蛋白质水平上均有所增加。结论:MDMB-FUBINACA通过诱导促血管生成因子的表达来诱导血管生成过程的进展。这些发现旨在开发血管生成相关疾病的新疗法。
{"title":"MDMB-FUBINACA Influences Brain Angiogenesis and the Expression of VEGF, ANG-1, and ANG-2.","authors":"Laith Al-Eitan, Mishael Alkhawaldeh","doi":"10.2174/1570161121666230913093441","DOIUrl":"10.2174/1570161121666230913093441","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to explore the impact of the synthetic cannabinoid methyl 2-(1-(4- fluorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (MDMB-FUBINACA) on the angiogenesis process in human brain microvascular endothelial cells.</p><p><strong>Background: </strong>Synthetic cannabinoids (SCs) are substances that mimic the natural components found in the cannabis plant. SCs are considered prohibited substances that have a clear impact on the central nervous system (CNS).</p><p><strong>Objectives: </strong>The purpose of this study is to explore how MDMB-FUBINACA influences angiogenesis in human brain microvascular endothelial cells and to clarify the pathways related to the cannabinoid receptors.</p><p><strong>Methods: </strong>Human brain microvascular endothelial cells (hBMECs) were grown in the medium containing Dulbecco Modified Eagle Medium (DMEM/F12) using an endothelial cell growth kit. Endothelial cell viability was evaluated using the MTT test. Migration ability was measured using the Wound healing test. The angiogenic capability was measured using a Tube Formation assay. Real-time polymerase chain reaction (RT-PCR) was utilized to explore the mRNA concentrations following MDMBFUBINACA treatment. ELISA and Western blotting were also employed to measure the protein levels.</p><p><strong>Results: </strong>MDMB-FUBINACA greatly increases tube formation, endothelial cell proliferation, and migration. Pro-angiogenic factors such as angiopoietins 1 and 2 (ANG-1 and 2) and vascular endothelial growth factor (VEGF) were shown to be increased at both the RNA and protein levels.</p><p><strong>Conclusion: </strong>MDMB-FUBINACA induces the progression of the angiogenesis process by inducing the expression of pro-angiogenic factors. These findings aim toward developing novel treatments for angiogenesis- related disorders.</p>","PeriodicalId":11278,"journal":{"name":"Current vascular pharmacology","volume":" ","pages":"356-365"},"PeriodicalIF":4.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10245586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.2174/1570161121666230328110215
Jin Xu, Liyuan Zhu, Yingying Xie, Miao Zhang, Zixi Xiao, Rongkai Su, Tie Wen, Ling Liu
Background: Hypertriglyceridemia, is commonly found in patients with diabetes. Xuezhikang, an extract of red yeast rice, is effective in reducing cardiovascular events in Chinese patients with diabetes and coronary heart disease (CHD). Xuezhikang has been reported to significantly decrease the level of triglycerides (TG), a potential causal risk factor for myocardial infarction. On the basis of a similar reduction in low-density lipoprotein cholesterol, this study will evaluate the effect of xuezhikang on TG levels compared with pravastatin in patients with type 2 diabetes mellitus (T2DM) and dyslipidemia.
Methods: This is an open-label, multicenter, randomized controlled study to assess the effects of xuezhikang (1.2 g/day) and pravastatin (20 mg/day) on TG and other blood lipid parameters in patients with T2DM and dyslipidemia. A total of 114 patients will be enrolled and randomly assigned 1:1 to receive xuezhikang or pravastatin treatment for 6 weeks.
Result: The primary outcome measure is the change from baseline in fasting TG levels after 6 weeks. The change from baseline in other fasting and postprandial lipid parameters, and glucose profiles at 1, 2, and 4 h after a nutritious breakfast will also be explored.
Conclusion: This study will evaluate the effect of a 6-week treatment with xuezhikang compared with pravastatin on fasting and postprandial TG levels and other blood lipid parameters in patients with T2DM and dyslipidemia without atherosclerotic cardiovascular disease (ASCVD). The results will provide more information on optimizing the lipid control of patients with diabetes in the primary prevention of ASCVD.
{"title":"Effects of Xuezhikang versus Pravastatin on Triglyceride Level in Patients with T2DM and Dyslipidemia: Study Protocol for a Multicenter Randomized Controlled Trial.","authors":"Jin Xu, Liyuan Zhu, Yingying Xie, Miao Zhang, Zixi Xiao, Rongkai Su, Tie Wen, Ling Liu","doi":"10.2174/1570161121666230328110215","DOIUrl":"10.2174/1570161121666230328110215","url":null,"abstract":"<p><strong>Background: </strong>Hypertriglyceridemia, is commonly found in patients with diabetes. Xuezhikang, an extract of red yeast rice, is effective in reducing cardiovascular events in Chinese patients with diabetes and coronary heart disease (CHD). Xuezhikang has been reported to significantly decrease the level of triglycerides (TG), a potential causal risk factor for myocardial infarction. On the basis of a similar reduction in low-density lipoprotein cholesterol, this study will evaluate the effect of xuezhikang on TG levels compared with pravastatin in patients with type 2 diabetes mellitus (T2DM) and dyslipidemia.</p><p><strong>Methods: </strong>This is an open-label, multicenter, randomized controlled study to assess the effects of xuezhikang (1.2 g/day) and pravastatin (20 mg/day) on TG and other blood lipid parameters in patients with T2DM and dyslipidemia. A total of 114 patients will be enrolled and randomly assigned 1:1 to receive xuezhikang or pravastatin treatment for 6 weeks.</p><p><strong>Result: </strong>The primary outcome measure is the change from baseline in fasting TG levels after 6 weeks. The change from baseline in other fasting and postprandial lipid parameters, and glucose profiles at 1, 2, and 4 h after a nutritious breakfast will also be explored.</p><p><strong>Conclusion: </strong>This study will evaluate the effect of a 6-week treatment with xuezhikang compared with pravastatin on fasting and postprandial TG levels and other blood lipid parameters in patients with T2DM and dyslipidemia without atherosclerotic cardiovascular disease (ASCVD). The results will provide more information on optimizing the lipid control of patients with diabetes in the primary prevention of ASCVD.</p>","PeriodicalId":11278,"journal":{"name":"Current vascular pharmacology","volume":"21 3","pages":"211-217"},"PeriodicalIF":4.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9940878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.2174/1570161121666230220123207
Antonietta Gigante, Rosario Cianci
{"title":"Dual Blockade of the Renin-Angiotensin System in Glomerular Diseases.","authors":"Antonietta Gigante, Rosario Cianci","doi":"10.2174/1570161121666230220123207","DOIUrl":"https://doi.org/10.2174/1570161121666230220123207","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":11278,"journal":{"name":"Current vascular pharmacology","volume":"21 2","pages":"75-77"},"PeriodicalIF":4.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9804258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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