Cardioprotection during myocardial infarction in diabetic cardiomyopathy

IF 7.5 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

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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.

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糖尿病性心肌病心肌梗死期间的心脏保护

糖尿病患者发生糖尿病性心肌病（DCM）和急性心肌梗死（AMI）的风险增加。与非糖尿病心脏相比，DCM患者保护心脏免受AMI更具挑战性。我们研究AMI期间静脉给予阿托伐他汀是否对非糖尿病心脏的DCM有心脏保护作用。将Sprague-Dawley大鼠分为链脲佐菌素诱导的DCM组和正常血糖对照组。我们的DCM大鼠模型在5周时出现间质纤维化和心功能障碍。在这个时间点，所有动物进行ami诱导（冠脉结扎45min），缺血时静脉注射阿托伐他汀或载药。24h后处死动物进行心肌梗死面积分析和心脏组织取样。进行超声心动图检查。在同等危险区域，DCM载药大鼠的梗死面积大于血糖正常载药处理的动物。两组患者静脉注射阿托伐他汀均可减小梗死面积并保持收缩功能。与载药动物相比，静脉注射阿托伐他汀抑制RhoA膜易位，诱导AMPK磷酸化，阻止凋亡执行，改善梗死心脏重构，而静脉注射阿托伐他汀治疗的DCM动物的先天免疫细胞浸润进一步减少。在DCM存在的情况下，静脉注射他汀类药物已被证明具有心脏保护作用，这保证了其进一步发展成为临床治疗选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.