Journal of Cardiovascular Pharmacology最新文献_第6页

Ceramide-Phospholipid Risk Score Associates With Cardiovascular Events and Is Lowered by Atorvastatin, Simvastatin, and Anti-PCSK9 Treatments. 神经酰胺-磷脂风险评分与心血管事件相关，并通过阿托伐他汀、辛伐他汀和抗pcsk9治疗降低。

IF 2.5 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2026-08-01 Epub Date: 2026-07-20 DOI: 10.1097/FJC.0000000000001817

Mika Hilvo, Angelika Witoslawska, Mitja Lääperi, Antti Jylhä, Leo-Pekka Lyytikäinen, Hannu Päivä, Jari Laurikka, Winfried März, Pekka J Karhunen, Terho Lehtimäki, Reijo Laaksonen

{"title":"Ceramide-Phospholipid Risk Score Associates With Cardiovascular Events and Is Lowered by Atorvastatin, Simvastatin, and Anti-PCSK9 Treatments.","authors":"Mika Hilvo, Angelika Witoslawska, Mitja Lääperi, Antti Jylhä, Leo-Pekka Lyytikäinen, Hannu Päivä, Jari Laurikka, Winfried März, Pekka J Karhunen, Terho Lehtimäki, Reijo Laaksonen","doi":"10.1097/FJC.0000000000001817","DOIUrl":"10.1097/FJC.0000000000001817","url":null,"abstract":"Objective: The aim of the study was to investigate the prognostic value of previously established ceramide-phospholipid risk score, CERT2, and its response to lipid-lowering treatments in patients with symptomatic or suspected coronary heart disease.Approach and results: Selected ceramides and phospholipids were analyzed with a quantitative liquid chromatography-mass spectrometry-based method from plasma or serum samples obtained from the Angiography and Genes study (ANGES, N = 966), and placebo-controlled trials investigating atorvastatin and simvastatin (N = 44) and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor RG7652 (N = 78). In the ANGES, the adjusted hazard ratios (95% confidence interval) per SD for the CERT2 risk score were 1.71 (1.42-2.08) for cardiovascular disease death, 1.36 (1.13-1.64) for myocardial infarction, 1.40 (1.20-1.63) for heart failure, 1.23 (1.08-1.40) for atrial fibrillation, 1.09 (0.89-1.33) for stroke, and 1.52 (1.06-2.18) for venous thromboembolism. The median decrease of the CERT2 risk score was 2 points by statin treatment ( P ≤ 0.001) and 3 points by PCSK9 inhibition ( P < 0.001) on the 0-12 scale.Conclusions: The CERT2 risk score is a significant predictor of cardiovascular outcomes in all-comer patients with symptomatic or suspected coronary heart disease. Treatment with lipid-lowering medication significantly lowers the CERT2 risk score.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"161-165"},"PeriodicalIF":2.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Silencing Triglycerides: The Clinical Impact of Plozasiran and apoC-III Inhibition in Severe Hypertriglyceridemia. 沉默甘油三酯：plzasiran和apoC-III抑制对严重高甘油三酯血症的临床影响。

IF 2.5 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2026-08-01 Epub Date: 2026-07-20 DOI: 10.1097/FJC.0000000000001846

Belal A Kassem, Fawaz A Shaik, Omar Sorour, Alaa Abdelhamid, Alysse Fazal, Ali H Dakroub, Ali H Eid

{"title":"Silencing Triglycerides: The Clinical Impact of Plozasiran and apoC-III Inhibition in Severe Hypertriglyceridemia.","authors":"Belal A Kassem, Fawaz A Shaik, Omar Sorour, Alaa Abdelhamid, Alysse Fazal, Ali H Dakroub, Ali H Eid","doi":"10.1097/FJC.0000000000001846","DOIUrl":"10.1097/FJC.0000000000001846","url":null,"abstract":"Abstract: Severe hypertriglyceridemia (sHTG) is a critical metabolic disorder that substantially elevates the risk of atherosclerotic vascular disease and acute pancreatitis. Despite its clinical significance, many conventional triglyceride-lowering therapies often fail to adequately reduce triglyceride levels or prevent these life-threatening complications. This unmet need has spurred interest in targeting regulatory proteins involved in triglyceride metabolism, such as apolipoprotein C3, a key inhibitor of lipoprotein lipase activity that promotes triglyceride-rich lipoprotein accumulation. Plozasiran, an investigational small interfering RNA therapy, has emerged as a breakthrough in sHTG management by selectively degrading hepatic APOC3 messenger RNA. Indeed, clinical trials demonstrate this drug's robust efficacy in reducing triglyceride levels, concomitant with reduced non-high-density lipoprotein (HDL) cholesterol and apolipoprotein B-key markers of cardiovascular risk. Notably, the Phase III PALISADE trial in familial chylomicronemia syndrome patients revealed plozasiran's potential to mitigate acute pancreatitis risk by normalizing triglyceride levels with a favorable safety profile. Current guidelines emphasize a multimodal approach to sHTG, combining dietary restriction of fats and simple carbohydrates with pharmacotherapy. However, plozasiran's prolonged dosing interval and mechanism-based action position it as a transformative option, particularly for patients refractory to existing treatments. Although long-term cardiovascular outcome data remain pending, its ability to durably modulate APOC3 expression offers new hope for breaking the cycle of dyslipidemia-driven organ damage. As research progresses, this therapy may redefine standards of care for high-risk populations, bridging a critical gap in preventive cardiology and pancreatology.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"123-131"},"PeriodicalIF":2.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148329168","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}

引用次数: 0

Incretin-based therapies, alcohol and tobacco use, and acute substance-related events: emerging implications for cardiovascular medicine. 肠促胰岛素为基础的治疗，酒精和烟草使用，以及急性物质相关事件：对心血管医学的新影响。

IF 2.5 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2026-07-28 DOI: 10.1097/FJC.0000000000001862

Ovidio De Filippo, Francesco Bruno, Federico Giacobbe, Guglielmo Beccuti, Valentina Braia, Fabio Broglio, Fabrizio D'Ascenzo, Gaetano Maria De Ferrari, Gianluca Aimaretti, Thomas F Luescher

{"title":"Incretin-based therapies, alcohol and tobacco use, and acute substance-related events: emerging implications for cardiovascular medicine.","authors":"Ovidio De Filippo, Francesco Bruno, Federico Giacobbe, Guglielmo Beccuti, Valentina Braia, Fabio Broglio, Fabrizio D'Ascenzo, Gaetano Maria De Ferrari, Gianluca Aimaretti, Thomas F Luescher","doi":"10.1097/FJC.0000000000001862","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001862","url":null,"abstract":"Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual incretin agonists are now familiar drugs in obesity, diabetes, heart failure, and cardiovascular prevention. At the same time, a clinically relevant but molecule-specific human literature suggests that selected incretin-based therapies, particularly semaglutide for alcohol-related outcomes, may also modify alcohol use, tobacco use, and selected acute substance-related events. Alcohol currently has the strongest signal. Small randomized studies suggest semaglutide can reduce laboratory alcohol self-administration and craving, whereas an earlier exenatide trial was neutral overall but suggested benefit in participants with obesity. Large registry and EHR studies further associate GLP-1RA exposure with lower alcohol-related hospitalization, lower incident or recurrent alcohol use disorder, and lower alcohol-related event rates. Tobacco evidence is more limited but now includes a pilot smoking-cessation trial with exenatide and a target-trial emulation linking semaglutide with fewer tobacco use disorder-related healthcare encounters. Evidence beyond alcohol and tobacco, and tirzepatide specific evidence, remains preliminary, although lower rates of opioid overdose, alcohol intoxication, and cannabis use disorder have been reported in observational analyses. For cardiologists, the key question is not whether incretin therapies should be viewed as addiction drugs, but whether established cardiometabolic therapies may also modify cardiovascular relevant risk behaviors.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603407","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}

引用次数: 0

The Subclinical Window for Cardioprotection in Duchenne Muscular Dystrophy: A Systematic Review and Meta-analysis. 杜氏肌营养不良患者心脏保护的亚临床窗口：系统回顾和荟萃分析。

IF 2.5 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2026-07-28 DOI: 10.1097/FJC.0000000000001863

Feras Shatarat, Amer A Alomari, Osama Bdarnh, Jana Alkasasbeh, Rahaf Alshatarat, Besan Jaber, Esraa Alyateem, Reem Alwahsh, Ahmad Sami Othman, Hasan Sami Othman, Farah Thaer

{"title":"The Subclinical Window for Cardioprotection in Duchenne Muscular Dystrophy: A Systematic Review and Meta-analysis.","authors":"Feras Shatarat, Amer A Alomari, Osama Bdarnh, Jana Alkasasbeh, Rahaf Alshatarat, Besan Jaber, Esraa Alyateem, Reem Alwahsh, Ahmad Sami Othman, Hasan Sami Othman, Farah Thaer","doi":"10.1097/FJC.0000000000001863","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001863","url":null,"abstract":"Cardiomyopathy is a major cause of morbidity and mortality in Duchenne muscular dystrophy (DMD). Myocardial injury begins during a prolonged subclinical phase while left ventricular ejection fraction (LVEF) remains preserved, suggesting a potential therapeutic window for early cardioprotective intervention. This study evaluated whether cardioprotective pharmacotherapy initiated before overt ventricular dysfunction is associated with improved clinical outcomes in DMD. A systematic review and meta-analysis were conducted following PRISMA guidelines (PROSPERO: CRD420261353435). Randomized trials and observational studies evaluating early cardioprotective therapy were included. Effect estimates were pooled using random-effects models to account for between-study heterogeneity. Fourteen studies including 1,788 patients were included in the review. Early cardioprotective therapy was associated with a significantly reduced risk of death (HR 0.39, 95% CI 0.23-0.65; I2 = 0%; K = 3, N = 958), as well as a lower risk of clinically meaningful cardiac progression (HR 0.36, 95% CI 0.21-0.62; I2 = 21.5%) and progression to overt left ventricular dysfunction (HR 0.41, 95% CI 0.24-0.70; I2 = 12.0%). In contrast, early therapy was not associated with a significant change in short-term left ventricular ejection fraction (mean difference -0.14%, 95% CI -2.57 to 2.29; I2 = 0%). Early cardioprotective therapy initiated prior to overt ventricular dysfunction is associated with lower mortality and reduced progression of cardiomyopathy in Duchenne muscular dystrophy. These findings support the early initiation of cardioprotective therapy during the subclinical phase of Duchenne cardiomyopathy.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603350","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}

引用次数: 0

The Cardiac Sarcomere: From development of heritable cardiomyopathies to gene and precision therapies. 心脏肌瘤：从遗传性心肌病的发展到基因和精确治疗。

IF 2.5 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2026-07-07 DOI: 10.1097/FJC.0000000000001828

Yun Shi, Brittany N Balint, Paula F Nieto Morales, Andrew P Landstrom

{"title":"The Cardiac Sarcomere: From development of heritable cardiomyopathies to gene and precision therapies.","authors":"Yun Shi, Brittany N Balint, Paula F Nieto Morales, Andrew P Landstrom","doi":"10.1097/FJC.0000000000001828","DOIUrl":"10.1097/FJC.0000000000001828","url":null,"abstract":"The cardiac sarcomere forms the fundamental contractile unit of the myocardium, and its precise structural and regulatory integrity is essential for normal cardiac function. Over the past several decades, advances in functional and structural biology, as well as molecular genetics, have improved our understanding of how sarcomeric protein dysfunction gives rise to inherited cardiomyopathies. This review combines current knowledge on sarcomere-associated hypertrophic cardiomyopathy and dilated cardiomyopathy, focusing on clinical presentation, genetic basis, and the mechanisms that link pathogenic variants to phenotypic manifestations. We highlight how disease-associated variants in sarcomeric genes, such as MYBPC3 , MYH7 , TNNC1 , TNNI3 and TNNT2 , perturb force generation, calcium handling, and myofilament turnover, ultimately driving hypertrophic or dilated phenotypes through distinct, yet overlapping, molecular cascades. Emerging sarcomere-targeted small molecular and gene therapies are discussed, including small-molecule myosin modulators, RNA-based strategies, and in vivo gene-editing approaches aimed at halting or reversing disease progression. These sarcomere-directed precision therapeutics are promising avenues in the treatment of inherited cardiomyopathies and other cardiovascular diseases.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396699","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}

引用次数: 0

Targeted Therapies in Hypertrophic Cardiomyopathy: A Practical Review of Evidence, Implementation, and Innovation. 肥厚性心肌病的靶向治疗：证据、实施和创新的实践回顾。

IF 2.5 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2026-07-06 DOI: 10.1097/FJC.0000000000001843

Madeline P Smoot, James P MacNamara, Michael P Ayers

{"title":"Targeted Therapies in Hypertrophic Cardiomyopathy: A Practical Review of Evidence, Implementation, and Innovation.","authors":"Madeline P Smoot, James P MacNamara, Michael P Ayers","doi":"10.1097/FJC.0000000000001843","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001843","url":null,"abstract":"Hypertrophic cardiomyopathy (HCM) is a common inherited disorder characterized by sarcomere dysfunction leading to myocardial hypertrophy, diastolic impairment, and, in many patients can result in dynamic left ventricular outflow tract obstruction (LVOTO). Traditional pharmacologic management of HCM has relied on β-blockers and nondihydropyridine calcium channel blockers, which provide symptomatic relief but do not directly target underlying molecular pathology of the disease. Advances in mechanistic understanding of HCM, particularly the role of hyperactive actin-myosin cross-bridge cycling, have led to the development of cardiac myosin inhibitors (CMIs), a novel class of targeted therapeutics. This review systematically summarizes the pharmacology, clinical trial evidence, dosing strategies, and safety considerations surrounding CMIs. While CMIs have transformed the management of obstructive HCM, their role in non-obstructive HCM disease remains uncertain, highlighting ongoing unmet needs. Emerging therapies, including next-generation myosin modulators, metabolic agents, sodium-glucose cotransporter inhibitors, and RNA-targeted approaches, offer promise for broader disease modification across all HCM phenotypes. As therapeutic options expand, combining pharmacology and clinical assessment endpoints in the treatment of HCM patients will be essential to define long-term benefit.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396684","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}

引用次数: 0

Olezarsen and Plozasiran: Novel apoC-III targeting medications for the treatment of hypertriglyceridemia. Olezarsen和Plozasiran：新型apoC-III靶向药物治疗高甘油三酯血症。

IF 2.5 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2026-07-06 DOI: 10.1097/FJC.0000000000001854

Michael S Kelly, Jelena Lewis, Dylan Zuch, Mikhayla R Rogowsky, Dave L Dixon

{"title":"Olezarsen and Plozasiran: Novel apoC-III targeting medications for the treatment of hypertriglyceridemia.","authors":"Michael S Kelly, Jelena Lewis, Dylan Zuch, Mikhayla R Rogowsky, Dave L Dixon","doi":"10.1097/FJC.0000000000001854","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001854","url":null,"abstract":"Hypertriglyceridemia is a prevalent lipid disorder associated with residual atherosclerotic cardiovascular disease (ASCVD) risk and increased risk of acute pancreatitis at triglyceride (TG) levels above 1000 mg/dL. Causes of hypertriglyceridemia are multifactorial and may be a result of secondary causes (Western diet, alcohol, medications, uncontrolled diseases/disorders), genetic disorders, or a combination of both. Two novel medications (olezarsen, plozasiran), which inhibit hepatic production of apoC-III mRNA and increase TG clearance, have recently been approved to reduce TG levels in adults with familial chylomicronemia syndrome (FCS). Both olezarsen and plozasiran have been evaluated in randomized, placebo-controlled, clinical trials in patients with varying degrees of hypertriglyceridemia. In this review, we report the lipid-lowering effects and safety of both olezarsen and plozasiran from clinical trials in patients with hypertriglyceridemia. Based on available data, both agents are associated with significant TG-lowering effects via reductions in apoC-III, as well as favorable effects on other lipid parameters. Overall, both agents appear generally well tolerated, although monitoring of liver enzymes and glycemic control is warranted for both agents, and additional monitoring of platelet counts for olezarsen. Future clinical trials are needed to assess whether the TG-lowering effects of each agent are associated with reduced risk of pancreatitis and ASCVD events.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396639","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}

引用次数: 0

Safety and Efficacy of Lorundrostat in Uncontrolled Hypertension: A Systematic Review and Meta-Analysis. Lorundrostat治疗未控制高血压的安全性和有效性：一项系统综述和荟萃分析。

IF 2.5 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2026-07-06 DOI: 10.1097/FJC.0000000000001857

Saad Ashraf, Shariq Ahmad Wani, Muhammad Burhan, Muhammad Abdullah Naveed, Fnu Anchal, Hamza Irfan, Bazil Azeem, Ahila Ali

{"title":"Safety and Efficacy of Lorundrostat in Uncontrolled Hypertension: A Systematic Review and Meta-Analysis.","authors":"Saad Ashraf, Shariq Ahmad Wani, Muhammad Burhan, Muhammad Abdullah Naveed, Fnu Anchal, Hamza Irfan, Bazil Azeem, Ahila Ali","doi":"10.1097/FJC.0000000000001857","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001857","url":null,"abstract":"Uncontrolled hypertension remains a major global health concern and a leading cause of cardiovascular morbidity and mortality. Aldosterone dysregulation plays a critical role in resistant hypertension, and Lorundrostat, a novel aldosterone synthase inhibitor, offers a promising therapeutic approach by directly inhibiting aldosterone production. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of Lorundrostat in adults with uncontrolled hypertension. Comprehensive searches of MEDLINE (PubMed), ScienceDirect, Google Scholar, and Cochrane databases were conducted up to July 2025 following PRISMA guidelines, with the protocol registered on PROSPERO (CRD420251091117). Three randomized controlled trials involving 1,568 participants (1,165 Lorundrostat and 403 placebo) were included, all demonstrating low risk of bias. Pooled analysis revealed that Lorundrostat significantly reduced systolic blood pressure (-8.50 mmHg, 95% CI -11.63 to -5.36, p < 0.00001) and diastolic blood pressure (-3.53 mmHg, 95% CI -5.61 to -1.45, p = 0.0009) compared with placebo, with no heterogeneity observed. However, Lorundrostat was associated with higher risks of hyperkalemia (RR = 5.84, p = 0.01), symptomatic hypotension (RR = 2.98, p = 0.03), serious adverse events (RR = 3.31, p = 0.03), and hyponatremia (RR = 2.03, p = 0.01), though there were no significant differences in moderate or severe adverse events or reduction in kidney function. Publication bias was noted for diastolic blood pressure and selected safety outcomes. In conclusion, Lorundrostat demonstrates clinically meaningful blood pressure reduction in uncontrolled hypertension compared with placebo, but with an increased risk of electrolyte disturbances and hypotension. Cautious use and close monitoring are warranted, and larger, long-term trials are needed to further define its safety and therapeutic role.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396653","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}

引用次数: 0

Human Histamine-1 Receptor Antagonism by Imipramine: Bridging Experimental Models and Clinical Cardiotoxicity. 丙咪嗪对人H1受体的拮抗作用：桥接实验模型和临床心脏毒性。

IF 2.5 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2026-07-01 DOI: 10.1097/FJC.0000000000001820

Martina Toldo, Jazmin Kelly, Adolfo G Mauro, Stefano Toldo

引用次数: 0

SGLT2 Inhibitors Attenuate Neutrophil-Mediated Endothelial Injury in Coronary Artery Disease With Type 2 Diabetes Mellitus Through a GREM1-Associated Smad Signaling Axis. SGLT2抑制剂通过grem1相关的Smad信号轴减轻中性粒细胞介导的冠心病合并T2DM内皮损伤。

IF 2.5 4区医学

Journal of Cardiovascular Pharmacology Pub Date : 2026-07-01 DOI: 10.1097/FJC.0000000000001836

Wenyuan Zheng, Yixin Zhou, Bozhi Ye, Shiyu Hu, Jian Zhang, Zhenwei Li, Xiaomin Chen, Jiatian Cao, Juying Qian, Junbo Ge

{"title":"SGLT2 Inhibitors Attenuate Neutrophil-Mediated Endothelial Injury in Coronary Artery Disease With Type 2 Diabetes Mellitus Through a GREM1-Associated Smad Signaling Axis.","authors":"Wenyuan Zheng, Yixin Zhou, Bozhi Ye, Shiyu Hu, Jian Zhang, Zhenwei Li, Xiaomin Chen, Jiatian Cao, Juying Qian, Junbo Ge","doi":"10.1097/FJC.0000000000001836","DOIUrl":"10.1097/FJC.0000000000001836","url":null,"abstract":"Abstract: Type 2 diabetes mellitus (T2DM) is a critical risk factor for coronary artery disease (CAD), with neutrophils contributing to CAD through acute inflammatory responses. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors offer cardiovascular benefits beyond glycemic control, but their mechanisms involving innate immunity and neutrophil function in T2DM-related CAD remain unclear. Neutrophils were isolated from healthy controls, patients with CAD and T2DM, and patients receiving SGLT2 inhibitor therapy. Bulk transcriptomic analysis, flow cytometry, ELISA, and western blotting were used to assess gene expression, signaling changes, and neutrophil activation. Co-cultures of neutrophils with luciferase-expressing human aortic endothelial cells (HAEC-Luc) assessed endothelial injury, and a diabetic rat model was used to assess in vivo cardiac injury. Results showed elevated peripheral neutrophil cell-free dsDNA, elastase 2, and GREM1 expression in patients with T2DM-CAD, reversed by SGLT-2 inhibitors. T2DM-CAD neutrophils induced significant endothelial injury, ameliorated by SGLT-2 inhibition, or GREM1 blockade. Mechanistically, SGLT-2 inhibitors suppressed GREM1, restored TGF-β/Smad signaling, and reduced neutrophil-mediated cytotoxicity. In vivo, SGLT-2 inhibitors alleviated cardiac damage in diabetic rat, with suppressed neutrophil activation and upregulated TGF-β signaling. Our findings suggest that increased GREM1 expression in neutrophils is associated with impaired Smad1/5/9-related signaling and enhanced endothelial injury in T2DM-CAD, and SGLT-2 inhibitors exert vascular protection through GREM1 downregulation and TGF-β/Smad pathway modulation, highlighting a novel immunoregulatory mechanism with translational potential for diabetic cardiovascular outcomes.","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"25-35"},"PeriodicalIF":2.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13344405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148329196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0