Cardioprotection during myocardial infarction in diabetic cardiomyopathy

IF 6.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes Pub Date : 2025-03-13 DOI:10.2337/db24-0510

Sebastià Alcover, Sergi López, Lisaidy Ramos, Natàlia Muñoz-García, Alex Gallinat, Rosa Suades, Lina Badimon, Gemma Vilahur

{"title":"Cardioprotection during myocardial infarction in diabetic cardiomyopathy","authors":"Sebastià Alcover, Sergi López, Lisaidy Ramos, Natàlia Muñoz-García, Alex Gallinat, Rosa Suades, Lina Badimon, Gemma Vilahur","doi":"10.2337/db24-0510","DOIUrl":null,"url":null,"abstract":"Diabetic patients are at an increased risk of diabetic cardiomyopathy (DCM) and acute myocardial infarction (AMI). Protecting the heart against AMI is more challenging in DCM than non-diabetic hearts. We investigated whether intravenous atorvastatin administration during AMI exerts cardioprotection in DCM as seen in non-diabetic hearts. Sprague-Dawley rats were divided into streptozotocin-induced DCM and normoglycemic-control groups. Our model of DCM rats exhibited interstitial fibrosis and cardiac dysfunction at 5 weeks. At this time point, all animals underwent AMI-induction (coronary ligation for 45min), receiving intravenous atorvastatin or vehicle during ischemia. Animals were reperfused and sacrificed 24h later for myocardial infarct size analysis and cardiac tissue sampling. Echocardiography was performed. DCM vehicle rats had larger infarcts than normoglycemic vehicle-treated animals at comparable area-at-risk. Intravenous atorvastatin reduced infarct size and preserved systolic function in both groups. In comparison to vehicle animals, intravenous atorvastatin inhibited RhoA membrane translocation, induced AMPK phosphorylation, prevented apoptosis execution and improved cardiac remodelling in the infarcted heart of both groups whereas innate immune cell infiltration was further reduced in intravenous atorvastatin-treated DCM animals. The proven cardioprotective effectiveness of this intravenous statin formulation in the presence of DCM warrants its further development into a clinically therapeutic option.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"9 1","pages":""},"PeriodicalIF":6.2000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2337/db24-0510","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Diabetic patients are at an increased risk of diabetic cardiomyopathy (DCM) and acute myocardial infarction (AMI). Protecting the heart against AMI is more challenging in DCM than non-diabetic hearts. We investigated whether intravenous atorvastatin administration during AMI exerts cardioprotection in DCM as seen in non-diabetic hearts. Sprague-Dawley rats were divided into streptozotocin-induced DCM and normoglycemic-control groups. Our model of DCM rats exhibited interstitial fibrosis and cardiac dysfunction at 5 weeks. At this time point, all animals underwent AMI-induction (coronary ligation for 45min), receiving intravenous atorvastatin or vehicle during ischemia. Animals were reperfused and sacrificed 24h later for myocardial infarct size analysis and cardiac tissue sampling. Echocardiography was performed. DCM vehicle rats had larger infarcts than normoglycemic vehicle-treated animals at comparable area-at-risk. Intravenous atorvastatin reduced infarct size and preserved systolic function in both groups. In comparison to vehicle animals, intravenous atorvastatin inhibited RhoA membrane translocation, induced AMPK phosphorylation, prevented apoptosis execution and improved cardiac remodelling in the infarcted heart of both groups whereas innate immune cell infiltration was further reduced in intravenous atorvastatin-treated DCM animals. The proven cardioprotective effectiveness of this intravenous statin formulation in the presence of DCM warrants its further development into a clinically therapeutic option.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Diabetes 医学-内分泌学与代谢

CiteScore

12.50

自引率

2.60%

发文量

1968

审稿时长

1 months

期刊介绍： Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.