Molecular Mechanisms of Retinoid Receptors in Diabetes-Induced Cardiac Remodeling.
Molecular Mechanisms of Retinoid Receptors in Diabetes-Induced Cardiac Remodeling.
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DOI：
10.3390/jcm3020566
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发表时间：
2014-06-04
影响因子：
3.9
通讯作者：
Baker KM
中科院分区：
文献类型：
--
作者：
Pan J;Guleria RS;Zhu S;Baker KM
糖尿病心肌病（DCM）是糖尿病患者发病率和死亡率的重要因素，其特征在于心室功能障碍，而不存在冠状动脉粥样硬化和高血压。由于缺乏对疾病过程的机械理解，没有有效治疗DCM患者的特定治疗策略。视黄酸是维生素A的活性代谢产物，通过结合和激活核受体：视黄酸受体（RAR）和类维生素A X受体（RXR）参与广泛的生物过程。RAR/RXR介导的信号转导与葡萄糖和脂质代谢的调节有关。近年来研究发现，RAR/RXR的激活通过改善心脏胰岛素抵抗、抑制细胞内氧化应激、NF-κ B介导的炎症反应以及调节肾素-血管紧张素系统，在预防糖尿病心肌病的发生发展中发挥重要作用。此外，下调RAR/RXR信号已被证明在糖尿病心肌，这表明受损的RAR/RXR信号可能是一个触发器，以加速糖尿病诱导的DCM的发展。了解维甲酸受体在糖尿病条件下调节心脏代谢和重塑的分子机制对于产生预防和治疗糖尿病诱导的心脏并发症和心力衰竭的新治疗方法提供动力是重要的。
Diabetic cardiomyopathy (DCM), a significant contributor to morbidity and mortality in diabetic patients, is characterized by ventricular dysfunction, in the absence of coronary atherosclerosis and hypertension. There is no specific therapeutic strategy to effectively treat patients with DCM, due to a lack of a mechanistic understanding of the disease process. Retinoic acid, the active metabolite of vitamin A, is involved in a wide range of biological processes, through binding and activation of nuclear receptors: retinoic acid receptors (RAR) and retinoid X receptors (RXR). RAR/RXR-mediated signaling has been implicated in the regulation of glucose and lipid metabolism. Recently, it has been reported that activation of RAR/RXR has an important role in preventing the development of diabetic cardiomyopathy, through improving cardiac insulin resistance, inhibition of intracellular oxidative stress, NF-κB-mediated inflammatory responses and the renin-angiotensin system. Moreover, downregulated RAR/RXR signaling has been demonstrated in diabetic myocardium, suggesting that impaired RAR/RXR signaling may be a trigger to accelerate diabetes-induced development of DCM. Understanding the molecular mechanisms of retinoid receptors in the regulation of cardiac metabolism and remodeling under diabetic conditions is important in providing the impetus for generating novel therapeutic approaches for the prevention and treatment of diabetes-induced cardiac complications and heart failure.