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Endothelial outgrowth cells shift macrophage phenotype and improve kidney viability in swine renal artery stenosis.

ABSTRACT: Endothelial outgrowth cells (EOC) decrease inflammation and improve endothelial repair. Inflammation aggravates kidney injury in renal artery stenosis (RAS), and may account for its persistence upon revascularization. We hypothesized that EOC would decrease inflammatory (M1) macrophages and improve renal recovery in RAS.Pigs with 10 weeks of RAS were studied 4 weeks after percutaneous transluminal renal angioplasty (PTRA+stenting) or sham, with or without adjunct intrarenal delivery of autologous EOC (10×10(6)), and compared with similarly treated normal controls (n=7 each). Single-kidney function, microvascular and tissue remodeling, inflammation, oxidative stress, and fibrosis were evaluated. Four weeks after PTRA, EOC were engrafted in injected RAS-kidneys. Stenotic-kidney glomerular filtration rate was restored in RAS+EOC, RAS+PTRA, and RAS+PTRA+EOC pigs, whereas stenotic-kidney blood flow and angiogenesis were improved and fibrosis attenuated only in EOC-treated pigs. Furthermore, EOC increased cell proliferation and decreased the ratio of M1 (inflammatory)/M2 (reparative) macrophages, as well as circulating levels and stenotic-kidney release of inflammatory cytokines. Cultured-EOC released microvesicles in vitro and induced phenotypic switch (M1-to-M2) in cultured monocytes, which was inhibited by vascular endothelial growth factor blockade. Finally, a single intrarenal injection of rh-vascular endothelial growth factor (0.05 ?g/kg) in 7 additional RAS pigs also restored M1/M2 ratio 4 weeks later.Intrarenal infusion of EOC after PTRA induced a vascular endothelial growth factor-mediated attenuation in macrophages inflammatory phenotype, preserved microvascular architecture and function, and decreased inflammation and fibrosis in the stenotic kidney, suggesting a novel mechanism and therapeutic potential for adjunctive EOC delivery in experimental RAS to improve PTRA outcomes.

SUBMITTER: Eirin A

PROVIDER: S-EPMC3644980 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Endothelial outgrowth cells shift macrophage phenotype and improve kidney viability in swine renal artery stenosis.

Eirin Alfonso A Zhu Xiang-Yang XY Li Zilun Z Ebrahimi Behzad B Zhang Xin X Tang Hui H Korsmo Michael J MJ Chade Alejandro R AR Grande Joseph P JP Ward Christopher J CJ Simari Robert D RD Lerman Amir A Textor Stephen C SC Lerman Lilach O LO

Arteriosclerosis, thrombosis, and vascular biology 20130221 5

<h4>Objective</h4>Endothelial outgrowth cells (EOC) decrease inflammation and improve endothelial repair. Inflammation aggravates kidney injury in renal artery stenosis (RAS), and may account for its persistence upon revascularization. We hypothesized that EOC would decrease inflammatory (M1) macrophages and improve renal recovery in RAS.<h4>Approach and results</h4>Pigs with 10 weeks of RAS were studied 4 weeks after percutaneous transluminal renal angioplasty (PTRA+stenting) or sham, with or w ...[more]

PMID: 23430615

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Dataset Information

Endothelial outgrowth cells shift macrophage phenotype and improve kidney viability in swine renal artery stenosis.

Publications

Endothelial outgrowth cells shift macrophage phenotype and improve kidney viability in swine renal artery stenosis.

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