Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in hypercholesterolemic patients and induces pro-angiogenic cytokine IL-8 secretion from monocytes.

Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in hypercholesterolemic patients and induces pro-angiogenic cytokine IL-8 secretion from monocytes. Research Abstract Details 

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Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in hypercholesterolemic patients and induces pro-angiogenic cytokine IL-8 secretion from monocytes. Abstract Text:

Kyung Woo Park,Kyung-Kuk Hwang,Hyun-Ju Cho,Jin Hur,Han-Mo Yang,Chang-Hwan Yoon,Hyun-Jae Kang,Byung-Hee Oh,Young-Bae Park,Hyo-Soo Kim,Kyung Woo Park,Kyung-Kuk Hwang,Hyun-Ju Cho,Jin Hur,Han-Mo Yang,Chang-Hwan Yoon,Hyun-Jae Kang,Byung-Hee Oh,Young-Bae Park,Hyo-Soo Kim,

BACKGROUND: Statins are known to have pleiotropic effects. We examined the effect and mechanism of simvastatin therapy on EPC differentiation and pro-angiogenic cytokines in patients with hypercholesterolemia. METHODS: Twenty-two hypercholesterolemia patients without any other modifiable cardiovascular risk factors or history of previous lipid-lowering therapy were given simvastatin 20 mg/day for 4 weeks. Blood were drawn pre- and post-therapy. The in vitro effects of simvastatin were studied in a separate set of experiments. RESULTS: Simvastatin treatment significantly increased the number of DiI-acLDL, UEA-1 lectin double-positive EPCs and facilitated its appearance. By FACS analysis of freshly isolated PBMNCs, KDR (+) cells increased after simvastatin treatment while there were no differences in CD34, AC133, and VE-cadherin. Also, serum concentration of IL-8 was markedly increased, while VEGF was only slightly increased. In vitro, PBMNCs co-cultured with simvastatin showed increased cluster formation at day 7, and simvastatin facilitated the appearance and networking of EPCs compared with vehicle. Simvastatin-co-cultured PBMNCs showed significantly increased KDR (+) cells, in contrast to CD34, CD31, and VE-Cadherin (+) cells. In response to simvastatin, IL-8 was mainly increased in monocyte culture supernatants while VEGF increased in smooth muscle cell culture supernatants. These cytokines were associated with increased EPC migratory function. The increase in IL-8 secretion from monocytes by statin treatment was associated with phosphorylation and inactivation of GSK3beta, which was reversed by constitutive activation of GSK-3beta. CONCLUSION: Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in patients with hypercholesterolemia and increases pro-angiogenic cytokine IL-8 secretion from monocytes. Our results may explain the pro-angiogenic effects associated with statin therapy and offer further evidence of statin pleiotropism.

Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in hypercholesterolemic patients and induces pro-angiogenic cytokine IL-8 secretion from monocytes. Publishing Authors By Initials

KW Park,KK Hwang,HJ Cho,J Hur,HM Yang,CH Yoon,HJ Kang,BH Oh,YB Park,HS Kim,KW Park,KK Hwang,HJ Cho,J Hur,HM Yang,CH Yoon,HJ Kang,BH Oh,YB Park,HS Kim,

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Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in hypercholesterolemic patients and induces pro-angiogenic cytokine IL-8 secretion from monocytes. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Clinica chimica acta; international journal of cli

VOLUME: 388

Page Numbers: 156-66

Journal Abbreviation: Clin. Chim. Acta

ISSN: 0009-8981

DAY: 4

MONTH: 11

YEAR: 2007

Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in hypercholesterolemic patients and induces pro-angiogenic cytokine IL-8 secretion from monocytes. Information

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LANGUAGE: eng

NlmUniqueID: 1302422

Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in hypercholesterolemic patients and induces pro-angiogenic cytokine IL-8 secretion from monocytes. Keywords Mesh Terms:

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Grant and Affiliation Information for Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in hypercholesterolemic patients and induces pro-angiogenic cytokine IL-8 secretion from monocytes.

AFFILIATION: National Research Laboratory for Cardiovascular Stem Cell, Seoul, South Korea; Cardiovascular Center, Seoul National University Hospital, Seoul, South Korea.

Country: Netherlands

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MEDLINETA: Clin Chim Acta

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