Charité - Universitätsmedizin Berlin, Institute of Pharmacology, Max Rubner Center for Cardiovascular Metabolic Renal Research (MRC), Berlin, Germany.
Charité - Universitätsmedizin Berlin, Institute of Pharmacology, Max Rubner Center for Cardiovascular Metabolic Renal Research (MRC), Berlin, Germany.
Biochem Pharmacol. 2024 Apr;222:116062. doi: 10.1016/j.bcp.2024.116062. Epub 2024 Feb 17.
The angiotensin AT2 receptor (ATR), an important member of the "protective arm" of the renin-angiotensin system (RAS), has been recently defined as a therapeutic target in different pathological conditions. The ATR activates complex signalling pathways linked to cellular proliferation, differentiation, anti-inflammation, antifibrosis, and induction or inhibition of apoptosis. The anti-inflammatory effect of ATR activation is commonly associated with reduced fibrosis in different models. Current discoveries demonstrated a direct impact of ATRs on the regulation of cytokines, transforming growth factor beta1 (TGF-beta1), matrix metalloproteases (MMPs), and synthesis of the extracellular matrix components. This review article summarizes current knowledge on the ATR in regard to immunity, inflammation and fibrosis in the heart and blood vessels. In particular, the differential influence of the ATR on cardiovascular remodeling in preclinical models of myocardial infarction, heart failure and aneurysm formation are discussed. Overall, these studies demonstrate that ATR stimulation represents a promising therapeutic approach to counteract myocardial and aortic damage in cardiovascular diseases.
血管紧张素 AT2 受体（ATR）是肾素-血管紧张素系统（RAS）“保护臂”的重要成员，最近被定义为不同病理情况下的治疗靶点。ATR 激活与细胞增殖、分化、抗炎、抗纤维化以及诱导或抑制细胞凋亡相关的复杂信号通路。ATR 激活的抗炎作用通常与不同模型中的纤维化减少有关。目前的发现表明 ATR 对细胞因子、转化生长因子β1（TGF-β1）、基质金属蛋白酶（MMPs）和细胞外基质成分合成的调节有直接影响。本文综述了 ATR 在心脏和血管中的免疫、炎症和纤维化方面的最新知识。特别是，讨论了 ATR 在心肌梗死、心力衰竭和动脉瘤形成的临床前模型中对心血管重塑的不同影响。总的来说，这些研究表明，ATR 刺激代表了一种有前途的治疗方法，可以对抗心血管疾病中的心肌和主动脉损伤。
