Secretory products from epicardial adipose tissue from patients with type 2 diabetes impair mitochondrial β-oxidation in cardiomyocytes via activation of the cardiac renin–angiotensin system and induction of miR-208a

详细信息    查看全文

• 作者：Marcel Blumensatt ; Pia Fahlbusch ; Rebecca Hilgers…
• 关键词：Epicardial adipose tissue ; Angiotensin II ; Cardiomyocytes ; Contractile function ; Mitochondrial function ; MiR ; 208a
• 刊名：Basic Research in Cardiology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：112
• 期：1
• 全文大小：1,017 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Cardiology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1435-1803
• 卷排序：112

文摘

Secretory products from epicardial adipose tissue (EAT) from patients with type 2 diabetes (T2D) impair cardiomyocyte function. These changes associate with alterations in miRNA expression, including the induction of miR-208a. Recent studies suggest that activation of the cardiac-specific renin–angiotensin system (RAS) may affect cardiac energy metabolism via induction of miR-208a. This study investigated whether cardiomyocyte dysfunction induced by conditioned media (CM) from EAT-T2D involves activation of the RAS/miR-208a pathway. Therefore, primary adult rat cardiomyocytes were incubated with CM generated from EAT biopsies from patients with T2D and without T2D (ND). Exposing cardiomyocytes to CM-EAT-T2D reduced sarcomere shortening and increased miR-208a expression versus cells exposed to CM-EAT-ND or control medium. The angiotensin II receptor type 1 (AGTR1) antagonist losartan reversed these effects. Accordingly, incubation with angiotensin II (Ang II) reduced sarcomere shortening, and lowered palmitate-induced mitochondrial respiration and carnitine palmitoyltransferase 1c (CPT1c) expression in cardiomyocytes. Locked-nucleic-acid-mediated inhibition of miR-208a function reversed the detrimental effects induced by Ang II. Interestingly, Ang II levels in CM-EAT-T2D were increased by 2.6-fold after culture with cardiomyocytes. The paracrine activation of the cardiac-specific RAS by CM-EAT-T2D was corroborated by increases in the expression of AGTR1 and renin, as well as a reduction in angiotensin-converting enzyme 2 levels. Collectively, these data show that secretory products from EAT-T2D impair cardiomyocyte contractile function and mitochondrial β-oxidation via activation of the cardiac-specific RAS system and induction of miR-208a, and suggest that alterations in the secretory profile of EAT may contribute to the development of diabetes-related heart disease.