title: Gαq-protein carboxyl terminus imitation polypeptide GCIP-27 attenuates proliferation of vascular smooth muscle cells and vascular remodeling in spontaneously hypertensive rats.
abstract: 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+)](i) 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+)](i) 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.
authors.affiliation: Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, P.R. China.
authors.forename: Hai-Gang
authors.initials: HG
authors.lastname: Zhang
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Cheng
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Zhou
authors.forename: Yi
authors.initials: Y
authors.lastname: Jia
authors.forename: Xiu-Qin
authors.initials: XQ
authors.lastname: Wang
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Li
mesh_terms: D016475:3T3 Cells; D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001795:Blood Pressure Determination; D002118:Calcium / Q000032:analysis; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000502:physiology / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006984:Hypertrophy / Q000473:pathology* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D013778:Tetrazolium Salts; D013844:Thiazoles; D010738:Type C Phospholipases / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D002316:Cardiotonic Agents; C572754:GCIP-27 peptide; D010455:Peptides; D013778:Tetrazolium Salts; D013844:Thiazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D003094:Collagen; D010738:Type C Phospholipases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; C022616:thiazolyl blue; D019808:Losartan; D002118:Calcium