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

Brian J. Siroky, Hong Yin, Bradley P. Dixon, Ryan J. Reichert, Anna R. Hellmann, Thiruvamoor Ramkumar, Zenta Tsuchihashi, Marlene Bunni, Joshua Dillon, P. Darwin Bell, Julian R. Sampson, John Bissler

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume307
Issue number5
DOIs
StatePublished - Sep 1 2014

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Angiomyolipoma
Pericytes
Angiotensin Receptors
Tuberous Sclerosis
Kidney
Vascular Endothelial Growth Factor Receptor
Valsartan
Therapeutics
Vascular Endothelial Growth Factor D
Platelet-Derived Growth Factor Receptors
Polycystic Kidney Diseases
Desmin
Collagen Type IV
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Adipocytes
Vascular Endothelial Growth Factor A
Smooth Muscle
Blood Vessels
Actins

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy. / Siroky, Brian J.; Yin, Hong; Dixon, Bradley P.; Reichert, Ryan J.; Hellmann, Anna R.; Ramkumar, Thiruvamoor; Tsuchihashi, Zenta; Bunni, Marlene; Dillon, Joshua; Bell, P. Darwin; Sampson, Julian R.; Bissler, John.

In: American Journal of Physiology - Renal Physiology, Vol. 307, No. 5, 01.09.2014.

Research output: Contribution to journalArticle

Siroky, BJ, Yin, H, Dixon, BP, Reichert, RJ, Hellmann, AR, Ramkumar, T, Tsuchihashi, Z, Bunni, M, Dillon, J, Bell, PD, Sampson, JR & Bissler, J 2014, 'Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy', American Journal of Physiology - Renal Physiology, vol. 307, no. 5. https://doi.org/10.1152/ajprenal.00569.2013
Siroky, Brian J. ; Yin, Hong ; Dixon, Bradley P. ; Reichert, Ryan J. ; Hellmann, Anna R. ; Ramkumar, Thiruvamoor ; Tsuchihashi, Zenta ; Bunni, Marlene ; Dillon, Joshua ; Bell, P. Darwin ; Sampson, Julian R. ; Bissler, John. / Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy. In: American Journal of Physiology - Renal Physiology. 2014 ; Vol. 307, No. 5.
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