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

Siroky, B. J., Yin, H., Dixon, B. P., Reichert, R. J., Hellmann, A. R., Ramkumar, T., Tsuchihashi, Z., Bunni, M., Dillon, J., Bell, P. D., Sampson, Julian Roy ORCID: https://orcid.org/0000-0002-2902-2348 and Bissler, J. J. 2014. Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy. American Journal of Physiology-Renal Physiology 307 (5) , F560-F570. 10.1152/ajprenal.00569.2013

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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 TSC2- polycystic kidney disease 1 deletion syndrome and hypertension that were treated from an early age with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers compared with patients who did not receive this therapy. TSC-associated renal angiomyolipomas expressed ANG II type 1 receptors, platelet-derived growth factor receptor-β, desmin, α-smooth muscle actin, and VEGF receptor 2 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 VEGF-A, VEGF-D, soluble VEGF receptor 2, and collagen type IV. These findings suggest that angiomyolipomas may arise from renal pericytes. ANG II treatment of angiomyolipoma cells in vitro resulted in an exaggerated intracellular Ca2+ response and increased proliferation, which were blocked by the ANG II type 2 receptor antagonist valsartan. Blockade of ANG II signaling may have preventative therapeutic potential for angiomyolipomas.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	tuberous sclerosis complex; angiomyolipoma; angiotensin II type 1; receptor; pericyte; perivascular epithelioid cell tumor; mammalian target of rapamycin
Publisher:	American Physiological Society
ISSN:	1931-857X
Date of Acceptance:	6 June 2014
Last Modified:	01 Nov 2022 09:47
URI:	https://orca.cardiff.ac.uk/id/eprint/89239

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