Novel Insights into the Cardioprotective Effects of the Peptides of the Counter-Regulatory Renin–Angiotensin System

Currently, cardiovascular diseases are a major contributor to morbidity and mortality worldwide, having a significant negative impact on both the economy and public health. The renin–angiotensin system contributes to a high spectrum of cardiovascular disorders and is essential for maintaining normal cardiovascular homeostasis. Overactivation of the classical renin–angiotensin system is one of the most important pathophysiological mechanisms in the progression of cardiovascular diseases. The counter-regulatory renin–angiotensin system is an alternate pathway which favors the synthesis of different peptides, including Angiotensin-(1-7), Angiotensin-(1-9), and Alamandine. These peptides, via the angiotensin type 2 receptor (AT2R), MasR, and MrgD, initiate multiple downstream signaling pathways that culminate in the activation of various cardioprotective mechanisms, such as decreased cardiac fibrosis, decreased myocardial hypertrophy, vasodilation, decreased blood pressure, natriuresis, and nitric oxide synthesis. These cardioprotective effects position them as therapeutic alternatives for reducing the progression of cardiovascular diseases. This review aims to show the latest findings on the cardioprotective effects of the main peptides of the counter-regulatory renin–angiotensin system.