Gαq-protein carboxyl terminus imitation polypeptide GCIP-27 attenuates proliferation of vascular smooth muscle cells and vascular remodeling in spontaneously hypertensive rats.

Gq-protein is located at the convergent point in signal transduction pathways leading to vascular remodeling. The carboxyl terminus of Gα-subunit plays a vital role in G-protein-receptor interaction. The present study was designed to explore the effects of a synthetic Gαq carboxyl terminus imitation peptide, namely GCIP-27, on vascular smooth muscle cells (VSMC) in vitro and vascular remodeling in spontaneous hypertensive rats (SHR). Hyperplasia and hypertrophy of VSMC wre determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, [(3)H]-thymidine and [(3)H]-leucine incorporation, and Ca(2+) was measured with Fluo-3/AM staining. Systolic blood pressure (SBP), the ratio of media thickness to lumen diameter (MT/LD) of aorta, collagen content, and phospholipase C activity in aorta were measured in SHR. GCIP-27 (3-100 µg/l) significantly decreased proliferation activity, protein content, incorporation of [(3)H]-thymidine and [(3)H]-leucine, and Ca(2+) level in VSMC. SBP, MT/LD, collagen content, and phospholipase C activity in aorta of SHR were decreased significantly in GCIP-27 (7, 20, 60 µg/kg)-treated groups and losartan (6 mg/kg) group compared with vehicle group. In conclusion, GCIP-27 could inhibit vascular remodeling effectively in vitro and in vivo.