S-Space College of Medicine/School of Medicine (의과대학/대학원) Molecular and Genomic Medicine (분자유전체의학전공) Journal Papers (저널논문_분자유전체의학전공)
Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in hypercholesterolemic patients and induces pro-angiogenic cytokine IL-8 secretion from monocytes
- Park, Kyung Woo; Hwang, Kyung-Kuk; Cho, Hyun-Ju; Hur, Jin; Yang, Han-Mo; Yoon, Chang-Hwan; Kang, Hyun-Jae; Oh, Byung-Hee; Park, Young-Bae; Kim, Hyo-Soo
- Issue Date
- Clin Chim Acta. 2008 Feb;388(1-2):156-66. Epub 2007 Nov 4.
- Animals; Cell Differentiation/*drug effects; Cells, Cultured; Endothelial Cells/*cytology/drug effects/secretion; Humans; Hypercholesterolemia/*metabolism; Interleukin-8/*secretion; Mice; Monocytes/*cytology/drug effects/*secretion; Simvastatin/*pharmacology; Vascular Endothelial Growth Factor A/secretion
- 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.
- 0009-8981 (Print)
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