Journal
FASEB JOURNAL
Volume 20, Issue 10, Pages 1706-+Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.05-5680fje
Keywords
kidney; ischemia; simvastatin; angiogenesis; microvessels; remodeling
Categories
Funding
- NHLBI NIH HHS [HL-77131] Funding Source: Medline
- NIBIB NIH HHS [EB 000305] Funding Source: Medline
- NIDDK NIH HHS [DK-73608] Funding Source: Medline
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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 electronbeam- 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-steno-sis arteriogenesis and increased the expression of angiogenic growth factors and hypoxia-inducible factor-1 alpha . 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.
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