Cortical microvascular remodeling in the stenotic kidney: Role of increased oxidative stress

Xiang Yang Zhu, Alejandro R. Chade, Martin G Rodriguez-Porcel, Michael D. Bentley, Erik L. Ritman, Amir Lerman, Lilach O Lerman

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

Objective - Mechanisms of renal injury distal to renal artery stenosis (RAS) remain unclear. We tested the hypothesis that it involves microvascular remodeling consequent to increased oxidative stress. Methods and Results - Three groups of pigs (n=6 each) were studied after 12 weeks of RAS, RAS+antioxidant supplementation (100 IU/kg vitamin E and 1 g vitamin C daily), or controls. The spatial density and tortuousity of renal microvessels (<500 μm) were tomographically determined by 3D microcomputed tomography. The in situ production of superoxide anion and the expression of vascular endothelial growth factor (VEGF), its receptor VEGFR-2, hypoxia-inducible-factor (HIF)-1α, von Hippel-Lindau (VHL) protein, and NAD(P)H oxidase (p47phox and p67phox subunits) were determined in cortical tissue. RAS and RAS+antioxidant groups had similar degrees of stenosis and hypertension. The RAS group showed a decrease in spatial density of cortical microvessels, which was normalized in the RAS+antioxidant group, as was arteriolar tortuousity. RAS kidneys also showed tissue fibrosis (by trichrome and Sirius red staining), increased superoxide anion abundance, NAD(P)H oxidase, VHL protein, and HIF-1α mRNA expression. In contrast, expression of HIF-1α, VEGF, and VEGFR-2 protein was downregulated. These were all significantly improved by antioxidant intervention. Conclusions - Increased oxidative stress in the stenotic kidney alters growth factor activity and plays an important role in renal microvascular remodeling, which can be prevented by chronic antioxidant intervention.

Original languageEnglish (US)
Pages (from-to)1854-1859
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume24
Issue number10
DOIs
StatePublished - Oct 2004

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Renal Artery Obstruction
Oxidative Stress
Kidney
Hypoxia-Inducible Factor 1
Antioxidants
Vascular Endothelial Growth Factor Receptor-2
NADPH Oxidase
Microvessels
Superoxides
X-Ray Microtomography
Vascular Endothelial Growth Factor Receptor
Proteins
Vitamin E
Vascular Endothelial Growth Factor A
Ascorbic Acid
Intercellular Signaling Peptides and Proteins
Pathologic Constriction
Fibrosis
Swine
Down-Regulation

Keywords

  • Free radicals/free-radical scavenger
  • Oxidative stress
  • Renal artery stenosis
  • Vascular biology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Cortical microvascular remodeling in the stenotic kidney : Role of increased oxidative stress. / Zhu, Xiang Yang; Chade, Alejandro R.; Rodriguez-Porcel, Martin G; Bentley, Michael D.; Ritman, Erik L.; Lerman, Amir; Lerman, Lilach O.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 24, No. 10, 10.2004, p. 1854-1859.

Research output: Contribution to journalArticle

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abstract = "Objective - Mechanisms of renal injury distal to renal artery stenosis (RAS) remain unclear. We tested the hypothesis that it involves microvascular remodeling consequent to increased oxidative stress. Methods and Results - Three groups of pigs (n=6 each) were studied after 12 weeks of RAS, RAS+antioxidant supplementation (100 IU/kg vitamin E and 1 g vitamin C daily), or controls. The spatial density and tortuousity of renal microvessels (<500 μm) were tomographically determined by 3D microcomputed tomography. The in situ production of superoxide anion and the expression of vascular endothelial growth factor (VEGF), its receptor VEGFR-2, hypoxia-inducible-factor (HIF)-1α, von Hippel-Lindau (VHL) protein, and NAD(P)H oxidase (p47phox and p67phox subunits) were determined in cortical tissue. RAS and RAS+antioxidant groups had similar degrees of stenosis and hypertension. The RAS group showed a decrease in spatial density of cortical microvessels, which was normalized in the RAS+antioxidant group, as was arteriolar tortuousity. RAS kidneys also showed tissue fibrosis (by trichrome and Sirius red staining), increased superoxide anion abundance, NAD(P)H oxidase, VHL protein, and HIF-1α mRNA expression. In contrast, expression of HIF-1α, VEGF, and VEGFR-2 protein was downregulated. These were all significantly improved by antioxidant intervention. Conclusions - Increased oxidative stress in the stenotic kidney alters growth factor activity and plays an important role in renal microvascular remodeling, which can be prevented by chronic antioxidant intervention.",
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T2 - Role of increased oxidative stress

AU - Zhu, Xiang Yang

AU - Chade, Alejandro R.

AU - Rodriguez-Porcel, Martin G

AU - Bentley, Michael D.

AU - Ritman, Erik L.

AU - Lerman, Amir

AU - Lerman, Lilach O

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N2 - Objective - Mechanisms of renal injury distal to renal artery stenosis (RAS) remain unclear. We tested the hypothesis that it involves microvascular remodeling consequent to increased oxidative stress. Methods and Results - Three groups of pigs (n=6 each) were studied after 12 weeks of RAS, RAS+antioxidant supplementation (100 IU/kg vitamin E and 1 g vitamin C daily), or controls. The spatial density and tortuousity of renal microvessels (<500 μm) were tomographically determined by 3D microcomputed tomography. The in situ production of superoxide anion and the expression of vascular endothelial growth factor (VEGF), its receptor VEGFR-2, hypoxia-inducible-factor (HIF)-1α, von Hippel-Lindau (VHL) protein, and NAD(P)H oxidase (p47phox and p67phox subunits) were determined in cortical tissue. RAS and RAS+antioxidant groups had similar degrees of stenosis and hypertension. The RAS group showed a decrease in spatial density of cortical microvessels, which was normalized in the RAS+antioxidant group, as was arteriolar tortuousity. RAS kidneys also showed tissue fibrosis (by trichrome and Sirius red staining), increased superoxide anion abundance, NAD(P)H oxidase, VHL protein, and HIF-1α mRNA expression. In contrast, expression of HIF-1α, VEGF, and VEGFR-2 protein was downregulated. These were all significantly improved by antioxidant intervention. Conclusions - Increased oxidative stress in the stenotic kidney alters growth factor activity and plays an important role in renal microvascular remodeling, which can be prevented by chronic antioxidant intervention.

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KW - Free radicals/free-radical scavenger

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