TRPC5 as a possible therapeutic target for vascular dysfunction associated with obesity
TRPC5 as a possible therapeutic target for vascular dysfunction associated with obesity
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DOI：
10.1038/s41440-022-01022-y
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发表时间：
2022-09
影响因子：
5.4
通讯作者：
H. Wakui;Moe Ozawa;K. Tamura
中科院分区：
文献类型：
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作者：
H. Wakui;Moe Ozawa;K. Tamura
肥胖症在世界范围内日益普遍，已成为现代社会的主要健康问题之一。自1980年以来，超过70个国家的肥胖患者数量翻了一番，2015年在195个国家中有1.077亿儿童和6.037亿成人被诊断患有肥胖症[1]。肥胖对代谢稳态产生负面影响，是2型糖尿病和动脉粥样硬化的危险因素，导致心血管疾病和死亡[2]。动脉粥样硬化是由血管内皮疾病引发的。内皮细胞通过血管活性因子平衡内皮依赖性舒张（EDR）和内皮依赖性收缩（EDC）来调节血管张力。在肥胖症中，炎症和氧化应激引起内皮功能障碍，导致EDR降低和EDC增加，从而导致动脉粥样硬化和增加心血管疾病的风险[3，4]。因此，阐明内皮功能障碍的机制，在肥胖可能导致临床应用，为预防心血管疾病。TRP通道是一个家庭的阳离子通道，作为细胞传感器感知外界环境的变化，并将此信息转化为阳离子/Ca 2+内流。TRPC 5是TRP通道家族的成员，在多种细胞类型中内源性表达，如血管内皮细胞、血管平滑肌细胞、心肌细胞和动脉压力感受器神经元。据报道，TRPC 5参与病理生理学，如动脉粥样硬化和心脏肥大，以及血压调节[5]。
Obesity is increasingly prevalent worldwide and has become one of the major health problems of modern society. Since 1980, the number of obese patients has doubled in> 70 countries, with 107.7 million children and 603.7 million adults diagnosed with obesity in 195 countries in 2015 [1]. Obesity negatively affects metabolic homeostasis and is a risk factor for type 2 diabetes and atherosclerosis, which lead to cardiovascular disease and death [2]. Atherosclerosis is triggered by vascular endothelial disorders. Endothelial cells regulate vascular tone by balancing endothelium-dependent relaxation (EDR) and endothelium-dependent contraction (EDC) via vasoactive factors. In obesity, inflammation and oxidative stress cause endothelial dysfunction, resulting in decreased EDR and increased EDC, thereby leading to atherosclerosis and increasing the risk of cardiovascular disease [3, 4]. Thus, elucidation of the mechanism of endothelial dysfunction in obesity may lead to clinical applications for the prevention of cardiovascular disease.TRP channels are a family of cation channels that act as cellular sensors to perceive changes in the external environment and convert this information into cation/Ca2+ influx. TRPC5, a member of the TRP channel family, is endogenously expressed in multiple cell types, such as vascular endothelial cells, vascular smooth muscle cells, cardiac myocytes, and arterial baroreceptor neurons. TRPC5 is reportedly involved in pathophysiologies such as atherosclerosis and cardiac hypertrophy, as well as in blood pressure regulation [5].