The ACE2/Apelin Signaling, MicroRNAs, and Hypertension

Figure 1

The crosstalk between ACE2/Apelin signaling and miRNAs in hypertension. On one hand, the miR-145 and miR-27a/b suppress the action of ACE/Ang II/AT1R, whereas miR-143 and miR-421 serve as negative regulators of ACE2 to modulate the balance between Ang II degradation and Ang-(1-7) generation. Overexpression of miR-155 inhibits the effects mediated by Ang II/AT1R signaling while Ang II regulates miR-138 and miR-132/212 expression via its receptor AT1R, contributing to cardiovascular hypertrophy and remodeling and elevated blood pressure. In contrast, Ang-(1-7) promotes the level of miR-146a, which blocks inflammation and cardiovascular remodeling. On the other hand, the Apelin/APJ signaling regulates the expression of miR-133a, miR-208, and miR-1, functioning as negative regulators for cardiac hypertrophy and contractile function. Moreover, the Apelin/APJ ameliorates cardiovascular hypertrophy and remodeling by modulating miR-424/-503-FGF signaling. ACE: angiotensin converting enzyme; ACE2: angiotensin converting enzyme 2; Ang II: angiotensin; AT1R: angiotensin II type 1 receptor; miRNAs: microRNAs; FGF2: fibroblast growth factor 2; FGFR1: fibroblast growth factor receptor 1.