(Pro)renin Receptor Regulates LDL-C Metabolism and Exacerbates Atherosclerosis via SREBP2/PCSK9/LDLR Pathway

As part of the renin-angiotensin system, the (pro)renin receptor [(P)RR] may participate in physiological processes via angiotensin II (Ang II)-independent pathways.Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerotic cardiovascular disease.Thus, it is necessary to explore whether (P)RR regulates LDL-C metabolism.We found that (P)RR activation enhanced LDL-C levels and contributed to atherosclerosis via an Ang II-independent pathway.This effect was mediated by proprotein convertase subtilisin kexin type 9 (PCSK9) and the low-density lipoprotein receptor (LDLR), providing mechanistic evidence supporting for its potential clinical relevance.