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Activation of G‐protein‐coupled estrogen receptor (GPER) inhibits coronary artery smooth muscle cell proliferation
Author(s) -
Li Fen,
Wang Gang,
Zhou Beiyan,
White Richard,
Heaps Cristine,
Stallone John,
Han Guichun
Publication year - 2012
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.26.1_supplement.663.9
Subject(s) - gper , vascular smooth muscle , cell growth , protein kinase b , estrogen receptor , endocrinology , medicine , cell cycle , flow cytometry , microbiology and biotechnology , population , chemistry , biology , cell , phosphorylation , smooth muscle , biochemistry , cancer , breast cancer , environmental health
One aspect of the beneficial influences of 17β‐estradiol on vascular smooth muscle cells (VSMC) is inhibition of VSMC proliferation following vascular injury. GPER is a potential mediator of estrogen action on coronary arteries, but whether GPER plays a role in coronary artery smooth muscle proliferation has never been reported. The objective of our study was to test the functional role of GPER in human and porcine coronary (CASMC) proliferation by applying flow cytometric analysis and Western blotting. The results are as follows: G‐1 (GPER agonist) inhibited both human and porcine CASMC proliferation in a concentration and time‐dependent manner (10 −8 to 10 −5 M). Flow cytometry revealed that G‐1 significantly decreased the proportion of S‐phase and G2/M cells in the growing cell population (stimulated by 10% charcoal/dextron striped FBS or 10 nM PDGF‐BB), suggesting that G‐1‐induces cell proliferation by slowing down the progression of the cell cycle. Western blot revealed that G‐1‐induced cell cycle retardation was associated with decreased expression of cyclinB, up‐regulation of cyclinD1, and concomitant induction of p21. G‐1 treatment also inhibited the phosphorylation of ERK1/2 and Akt. We conclude that GPER activation inhibits CASMC proliferation by retardation of cell cycle progression via inhibiting ERK1/2 and Akt activities.