Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy.

Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy. Am J Physiol Renal Physiol. 2014 Jun 11; Authors: Siroky BJ, Yin H, Dixon BP, Reichert RJ, Hellmann AR, Ramkumar T, Tsuchihashi Z, Bunni MA, Dillon J, Bell PD, Sampson JR, Bissler JJ Abstract Nearly all patients with tuberous sclerosis complex (TSC) develop renal angiomyolipomas, although the tumor cell of origin is unknown. We observed decreased renal angiomyolipoma development in patients with the TSC2-PKD1 deletion syndrome and hypertension that were treated from an early age with angiotensin converting enzyme inhibitors or angiotensin receptor blockers. TSC-associated renal angiomyolipomas expressed angiotensin II type 1 receptor, platelet derived growth factor receptor β and VEGFR2, but did not express the adipocyte marker S100 or the endothelial marker CD31. Sera of TSC patients exhibited increased vascular mural cell secreted peptides such as vascular endothelial growth factor (VEGF) D, sVEGFR2, and collagen IV. These findings suggest that angiomyolipomas may arise from renal pericytes. Angiotensin II treatment of angiomyolipoma cells in vitro resulted in an exaggerated intracellular calcium response and increased proliferation that were blocked by the angiotensin type II receptor 1 antagonist valsartan. Blockade of angiotensin II signaling may have preventative therapeutic potential for angiomyol...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research