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醛固酮受体在心血管和心肾疾病中的作用。

Roles of Mineralocorticoid Receptors in Cardiovascular and Cardiorenal Diseases.

机构信息

Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.

Laboratorio de Fisiología Cardiovascular y Trasplante Renal, Unidad de Investigación UNAM-INC, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.

出版信息

Annu Rev Physiol. 2022 Feb 10;84:585-610. doi: 10.1146/annurev-physiol-060821-013950.

Abstract

Mineralocorticoid receptor (MR) activation in the heart and vessels leads to pathological effects, such as excessive extracellular matrix accumulation, oxidative stress, and sustained inflammation. In these organs, the MR is expressed in cardiomyocytes, fibroblasts, endothelial cells, smooth muscle cells, and inflammatory cells. We review the accumulating experimental and clinical evidence that pharmacological MR antagonism has a positive impact on a battery of cardiac and vascular pathological states, including heart failure, myocardial infarction, arrhythmic diseases, atherosclerosis, vascular stiffness, and cardiac and vascular injury linked to metabolic comorbidities and chronic kidney disease. Moreover, we present perspectives on optimization of the use of MR antagonists in patients more likely to respond to such therapy and review the evidence suggesting that novel nonsteroidal MR antagonists offer an improved safety profile while retaining their cardiovascular protective effects. Finally, we highlight future therapeutic applications of MR antagonists in cardiovascular injury.

摘要

心脏和血管中的盐皮质激素受体 (MR) 激活会导致病理性效应,如细胞外基质过度积累、氧化应激和持续的炎症。在这些器官中,MR 在心肌细胞、成纤维细胞、内皮细胞、平滑肌细胞和炎症细胞中表达。我们回顾了越来越多的实验和临床证据,表明药理学 MR 拮抗作用对一系列心脏和血管病理性状态具有积极影响,包括心力衰竭、心肌梗死、心律失常性疾病、动脉粥样硬化、血管僵硬以及与代谢合并症和慢性肾病相关的心脏和血管损伤。此外,我们提出了优化 MR 拮抗剂在更可能对这种治疗有反应的患者中的使用的观点,并回顾了证据表明新型非甾体 MR 拮抗剂在保留其心血管保护作用的同时提供了改善的安全性。最后,我们强调了 MR 拮抗剂在心血管损伤中的未来治疗应用。

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