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,
,2
Department of Internal Medicine,
* Divisions of Nephrology and Hypertension and
Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota, USA;
Research Center of Excellence in Cardiovascular Diseases and Departments of General Pathology and Medicine, University of Naples, Italy; and
Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University, Boston, Massachusetts, USA
2Correspondence: Division of Nephrology and Hypertension, Mayo Clinic, 200 First St. S.W., Rochester, MN 55905, USA. E-mail: lerman.lilach{at}mayo.edu
ABSTRACT
We tested the hypothesis that statins would decrease renal injury in renal artery stenosis (RAS) by restoring angiogenesis and attenuating intrarenal microvascular (IMV) remodeling. Single-kidney hemodynamics and function were quantified using electron-beam-computed tomography (CT) in normocholesterolemic pigs after 12 wk of experimental RAS, RAS supplemented with simvastatin (RAS+simvastatin), and normal controls. Renal circulation was also studied in vivo using angiography and ex vivo using a unique 3D micro-CT imaging technique. Angiogenic and remodeling pathways were subsequently explored in renal tissue. Blood pressure and the degree of stenosis were similarly increased in RAS groups. Simvastatin in RAS enhanced both intrarenal angiogenesis and peri-stenosis arteriogenesis and increased the expression of angiogenic growth factors and hypoxia-inducible factor-1
. Furthermore, simvastatin decreased tissue-transglutaminase expression and IMV inward remodeling, restored IMV endothelial function, decreased fibrogenic activity, and improved renal function. Chronic simvastatin supplementation promoted angiogenesis in vivo, decreased ischemia-induced IMV remodeling, and improved IMV function in the stenotic kidney, independent of lipid lowering. These novel renoprotective effects suggest a role for simvastatin in preserving the ischemic kidney in chronic RAS.—Chade, A. R., Zhu, X., Mushin, O. P., Napoli, C., Lerman, A., Lerman, L. O. Simvastatin promotes angiogenesis and prevents microvascular remodeling in chronic renal ischemia.
This article has been cited by other articles:
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  A. R. Chade, J. D. Krier, O. Galili, A. Lerman, and L. O. Lerman Role of Renal Cortical Neovascularization in Experimental Hypercholesterolemia Hypertension, October 1, 2007; 50(4): 729 - 736. [Abstract] [Full Text] [PDF]
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 X.-Y. Zhu, E. Daghini, A. R. Chade, C. Napoli, E. L. Ritman, A. Lerman, and L. O. Lerman Simvastatin Prevents Coronary Microvascular Remodeling in Renovascular Hypertensive Pigs J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1209 - 1217. [Abstract] [Full Text] [PDF]
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