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29 August 2018 : Laboratory Research

Vasodilator-Stimulated Phosphoprotein: Regulators of Adipokines Resistin and Phenotype Conversion of Epicardial Adipocytes

Jing Wang1ABCDEF, Yan Jia1ABCDEF, Lijun Wang1ABCDEF, Demin Li2AB, Lei Wang1CD, Ying Zhu1CD, Jing Liu1CD, Jianbin Gong1ABCDEFG*

DOI: 10.12659/MSM.908111

Med Sci Monit 2018; 24: LBR6010-6020

Abstract

BACKGROUND: Endothelial dysfunction plays a central part in the pathogenesis of coronary atherosclerosis. The adipokine resistin is one of the key players in endothelial cell dysfunction. In addition, the role of epicardial fat in coronary artery endothelial dysfunction is also emphasized. We investigated whether vasodilator-stimulated phosphoprotein (VASP) is involved in resistin-related endothelial dysfunction and the phenotype conversion of epicardial adipocytes.

MATERIAL AND METHODS: Cell proliferation and migration were evaluated by MTT and Transwell chamber assay, respectively. Next, we took epicardial fat samples from patients with valvular heart disease and non- coronary artery disease. Gene expression was determined by reverse transcription- quantitative polymerase chain reaction and relative abundance of the protein by Western blotting.

RESULTS: Resistin induced endothelial proliferation and migration in a dose-dependent manner. Both resistin-induced cell proliferation and migration were effectively blocked by ablation of VASP. The brown adipose tissue-specific genes for uncoupling protein 1 (UCP-1) and PR-domain-missing16 (PRDM16) decreased, but the white adipose tissue-specific genes for resistin and RIP140 increased in VASP-deficient adipocytes compared with the LV-sicntr group. However, disruption of the Ras homolog gene family member A (RhoA) /Rho-associated kinase (ROCK) in VASP-deficient adipocytes with specific inhibitors inverted the adipocyte phenotype existing in VASP-deficient adipocytes. Furthermore, the expressions of proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractantprotein-1 (MCP-1) in VASP-deficient adipocytes were markedly upregulated compared with the LV-sicntr group.

CONCLUSIONS: These results suggest a physiological role for VASP in coronary atherosclerosis through regulating adipokine resistin and phenotype conversion of epicardial adipose tissue.

Keywords: Adipocytes, Brown, Adipocytes, White, cell migration, Coronary Artery Disease

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750