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Deficiency in CCR5 protects against vascular smooth muscle cell proliferation in mice fed with high fat diet
Author(s) -
Tsai Min Chien,
Tu YunChin,
Lee YenHsien,
Hsieh PoShiuan
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1196.6
Subject(s) - vascular smooth muscle , chemokine , biology , endocrinology , cyclin d1 , chemokine receptor , inflammation , medicine , ccr2 , proliferating cell nuclear antigen , cancer research , cell growth , cell cycle , apoptosis , immunology , biochemistry , smooth muscle
Chemokines play a crucial role in innate and inflammatory responses and in the pathophysiology of atherosclerosis. Chemokine‐chemokine receptors (CCR) are important modulators of inflammation although they have been shown to be involved in atherosclerosis progression. Previous studies have shown that vascular smooth muscle cells (VSMC) express functional chemokine‐chemokine receptors 5 (CCR5). However, little is known about how CCR5 is regulated in vascular smooth muscle cells. In this study, we analyzed the role of the CCR5 by genetic deletion in mice with a hyperlipidemia‐induced by high fat diet. Deficiency in CCR5 significantly reduced hyperplasia of the arterial wall after fed with a high fat diet for 12 weeks, associated with a decrease VSMC DNA synthase by proliferating cell nuclear antigen (PCNA) staining. Our data also show that deficiency of CCR5 inhibited VSMC proliferation by blocking G1 to S phase progression and repressed the phosphorylation of retinoblastoma protein (Rb). Furthermore, CCR5 knockout mice inhibited tumor necrosis factor‐alpha (TNF‐α)‐induced expression of cell cycle regulatory proteins such as cyclin E and CDK2. Collectively, this data provide an important role to characterize specific functions of the CCR5 in vascular pathology.