The (pro)renin receptor: pathophysiological roles in cardiovascular and renal pathology

Abstract

The pathophysiological role of the (pro)renin receptor is yet to be established. The present review summarizes the findings, suggesting that it may play pathological role in cardiac and renal fibrosis, and in hypertensive and diabetic nephropathy.In-vitro and animal studies have shown that increased receptor expression could be linked to high blood pressure and to cardiac and glomerular fibrosis by activating mitogen-activated protein kinases and by upregulating gene expression of profibrotic molecules. Studies also suggest that the receptor is involved in diabetic nephropathy by activating receptor-bound prorenin, thereby increasing angiotensin II tissue generation. Moreover, in diabetic mice, a peptide able to block prorenin binding to the receptor was claimed to be more effective for renal protection than angiotensin-converting enzyme inhibitor.The experimental data confirmed the pivotal role of the receptor in cell surface generation of angiotensin and suggested its potential role in tissue fibrosis via receptor activation and intracellular signaling. The data also questioned the ability of soon available renin inhibitors to inhibit the activity of receptor-bound renin and prorenin, and the benefit of a new class of drug--(pro)renin receptor blockers--to prevent tissue damage.