Simvastatin promotes angiogenesis and prevents microvascular remodeling in chronic renal ischemia

Alejandro R. Chade, Xiangyang Zhu, Oren P. Mushin, Claudio Napoli, Amir Lerman, Lilach O Lerman

Research output: Contribution to journalArticle

105 Citations (Scopus)

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-1α. 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.

Original languageEnglish (US)
JournalFASEB Journal
Volume20
Issue number10
DOIs
StatePublished - Aug 2006

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Renal Artery Obstruction
Simvastatin
ischemia
angiogenesis
Ischemia
kidneys
Kidney
arteries
Electron beam computed tomography
Pathologic Constriction
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypoxia-Inducible Factor 1
Angiography
Blood pressure
Hemodynamics
renal function
X Ray Computed Tomography
Angiogenesis Inducing Agents
Renal Circulation
Tomography

Keywords

  • Angiogenesis
  • Ischemia
  • Kidney
  • Microvessels
  • Remodeling
  • Simvastatin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Simvastatin promotes angiogenesis and prevents microvascular remodeling in chronic renal ischemia. / Chade, Alejandro R.; Zhu, Xiangyang; Mushin, Oren P.; Napoli, Claudio; Lerman, Amir; Lerman, Lilach O.

In: FASEB Journal, Vol. 20, No. 10, 08.2006.

Research output: Contribution to journalArticle

Chade, Alejandro R. ; Zhu, Xiangyang ; Mushin, Oren P. ; Napoli, Claudio ; Lerman, Amir ; Lerman, Lilach O. / Simvastatin promotes angiogenesis and prevents microvascular remodeling in chronic renal ischemia. In: FASEB Journal. 2006 ; Vol. 20, No. 10.
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