Leptin and endothelin-1 mediated increased extracellular matrix protein production and cardiomyocyte hypertrophy in diabetic heart disease

IF 6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes/Metabolism Research and Reviews Pub Date : 2009-04-23 DOI:10.1002/dmrr.964

Pijush Majumdar, Shali Chen, Biju George, Subhrojit Sen, Morris Karmazyn, Subrata Chakrabarti

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引用次数: 45

Abstract

Background

We investigated the role of leptin and its interaction with endothelin 1 (ET-1) in fibronectin (FN) synthesis and cardiomyocyte hypertrophy, two characteristic features of diabetic cardiomyopathy.

Methods

Endothelial cells [human umbilical vein endothelial cells (HUVECs)] were examined for FN production and neonatal rat cardiomyocytes for hypertrophy, following incubation with glucose, ET-1, leptin and specific blockers. FN, ET-1, leptin and leptin receptors mRNA expression and FN protein were measured. Myocytes were also morphometrically examined. Furthermore, hearts from streptozotocin-diabetic rats were analysed.

Results

Glucose caused increased FN mRNA and protein expression in HUVECs and cardiomyocytes hypertrophy along with upregulation of ET-1 mRNA, leptin mRNA and protein. Glucosemimetic effects were seen with leptin and ET-1. Leptin receptor antagonist (leptin quadruple mutant) and dual endothelin A endothelin B (ETA/ETB) receptor blocker bosentan normalized such abnormalities. Hearts from the diabetic animals showed hypertrophy and similar mRNA changes.

Conclusion

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瘦素和内皮素-1介导的糖尿病心脏病细胞外基质蛋白生成增加和心肌细胞肥大

我们研究了瘦素及其与内皮素1 (ET-1)在纤连蛋白(FN)合成和心肌细胞肥大中的作用，这是糖尿病性心肌病的两个特征。方法用葡萄糖、ET-1、瘦素和特异性阻滞剂孵育新生大鼠心肌细胞，检测内皮细胞(人脐静脉内皮细胞(HUVECs))的FN生成情况和心肌细胞的肥大情况。测定FN、ET-1、瘦素及瘦素受体mRNA表达和FN蛋白表达。肌细胞也进行了形态计量学检查。此外，对链脲佐菌素糖尿病大鼠的心脏进行了分析。结果葡萄糖引起huvec中FN mRNA和蛋白表达升高，ET-1 mRNA、瘦素mRNA和蛋白表达上调，心肌细胞肥大。瘦素和ET-1具有模拟糖的作用。瘦素受体拮抗剂(瘦素四重突变体)和双重内皮素A、内皮素B (ETA/ETB)受体阻滞剂波生坦使这种异常正常化。糖尿病动物的心脏出现肥大和类似的mRNA变化。结论糖尿病患者FN生成增加和心肌细胞肥大可能通过瘦素与ET-1相互作用介导。版权所有©2009 John Wiley &儿子,有限公司

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来源期刊

Diabetes/Metabolism Research and Reviews 医学-内分泌学与代谢

CiteScore

17.20

自引率

2.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Diabetes/Metabolism Research and Reviews is a premier endocrinology and metabolism journal esteemed by clinicians and researchers alike. Encompassing a wide spectrum of topics including diabetes, endocrinology, metabolism, and obesity, the journal eagerly accepts submissions ranging from clinical studies to basic and translational research, as well as reviews exploring historical progress, controversial issues, and prominent opinions in the field. Join us in advancing knowledge and understanding in the realm of diabetes and metabolism.