Update on RAAS Modulation for the Treatment of Diabetic Cardiovascular Disease

Figure 3

Tissue renin-angiotensin-aldosterone system. The activation of the RAAS cascade begins with renin secretion. Renin is secreted as a precursor protein, prorenin. Renin and prorenin can bind to their specific receptor called (P)RR and activate intracellular pathways independent of RAAS. Otherwise, renin cleaves angiotensinogen to form Ang I, which is then converted to Ang II by ACE. Ang II binds to its specific receptors: AT1R and AT2R. AT1R promotes blood pressure increase, cardiac remodeling, and atherosclerosis development. In addition, through AT1R, Ang II stimulates aldosterone secretion. On the other hand, AT2R seems to antagonize these effects. Moreover, Ang I and Ang II can be cleaved by ACE2 to form Ang 1–9 and Ang 1–7, which have opposite effects to those of Ang II, such as vasodilation, anti-inflammatory, antifibrotic, and antiremodeling effects, which are mediated by Mas1R and partly by AT2R. In addition, Ang 1–7 stimulates local ANP secretion. ACE is for angiotensin-converting enzyme; ACE2 is for angiotensin-converting enzyme 2; Ang is for angiotensin; AT1R is for Ang II type 1 receptor; AT2R is for Ang II type 2 receptor; ANP is for atrial natriuretic peptide; (P)RR is for (pro)renin receptor.