G_αq‐PROTEIN CARBOXYL TERMINUS IMITATION POLYPEPTIDE GCIP‐27 ATTENUATES CARDIAC HYPERTROPHY IN VITRO AND IN VIVO

Abstract

1. Various G(q)-protein-coupled receptors, such as alpha(1)-adrenoceptors, angiotension AT(1) receptors, endothelin ET(A) receptors, neuropeptide Y(1) receptors etc., contribute to cardiac hypertrophy. In G-protein signalling pathways, the carboxyl terminus of the G(alpha) subunit plays a vital role within G-protein-receptor interaction. The present study was designed to explore the effects of the synthetic G(alphaq) carboxyl terminal imitation peptide GCIP-27 on cardiac hypertrophy. 2. Hypertrophy of rat cultured cardiomyocytes was induced by noradrenaline (NA) or angiotensin (Ang) II in vitro. Protein content, [(3)H] incorporation and [Ca(2+)](i) were determined in cardiomyocytes cultured with GCIP-27. Three in vivo animal models of cardiac hypertrophy were prepared using intraperitoneal injections of NA in mice and rats and suprarenal abdominal aortic stenosis in rats. After treatment with GCIP-27 (10-100 microg/L) for 15 or 20 days, indices of cardiac hypertrophy were measured. The effect of GCIP-27 on the mRNA expression of c-fos and c-jun was detected using reverse transcription-polymerase chain reaction. 3. At 10-100 microg/L, GCIP-27 significantly decreased protein content and [(3)H]-leucine incorporation in cultured cardiomyocytes compared with 1 micromol/L NA- and 1 micromol/L AngII-treated groups. After treatment with GCIP-27 (10, 30 or 100 microg/kg) for 15 days, the heart index (HI) and left ventricular index (LVI) in mice decreased significantly compared with the NA control group. In rats, GCIP-27 significantly reduced HI and LVI compared with the NA and aortic stenosis groups. Moreover, [Ca(2+)](i) in cardiomyocytes in the GCIP-27 (3, 10, 30 microg/L)-treated groups was lower than that in the control groups. Expression of c-fos and c-jun mRNA decreased significantly in the myocardium from 5-45 microg/L GCIP-27-treated rats compared with NA controls. 4. The results indicate that GCIP-27 can attenuate cardiac hypertrophy effectively in various models in vitro and in vivo.

G.ALPHA.q-Protein Carboxyl Terminus Imitation Polypeptide (GCIP)-27 Inhibits Right Ventricular Hypertrophy Induced by Monocrotaline in Rats

“…GCIP-27, the optimized form of GCIP, could inhibit the left ventricular (LV) hypertrophy induced by NA in mice and induced by the aortic stenosis in rats, 14) and could also inhibit the LV remodeling in spontaneously hypertensive rats.…”

“…12) Gaq protein carboxyl terminus imitation polypeptide (GCIP), a peptide cloned and constructed in our laboratory previously, could inhibit the cardiomyocyte hypertrophy induced by noradrenaline (NA) in rats through acting as a competition candidate of the activated binding sites on Gaq. 13) GCIP-27, the optimized form of GCIP, could inhibit the left ventricular (LV) hypertrophy induced by NA in mice and induced by the aortic stenosis in rats, 14) and could also inhibit the LV remodeling in spontaneously hypertensive rats. 15) In addition, GCIP-27 could also prevent the hypertrophic responses in cultured rat cardiomyocytes induced by NA or Ang II.…”

“…15) In addition, GCIP-27 could also prevent the hypertrophic responses in cultured rat cardiomyocytes induced by NA or Ang II. 14) However, little is known about the effect of GCIP-27 on RV hypertrophy. Because the pathophysiology of RV remodeling is a complex process and may include unique elements not observed in LV remodeling, and the structure and function between the two chambers are very different, 1) it is necessary to characterize the effect of GCIP-27 on the RV remodeling.…”

Effects of allisartan, a new AT1 receptor blocker, on blood pressure and end-organ damage in hypertensive animals

“…Just below the branch of the left subclavicular artery, a 30-mm-long segment of thoracic aorta was harvested, blotted, and weighed. Ratios of ventricular weight to body weight (VW/BW), left ventricular weight to body weight (LVW/BW), right kidney weight to body weight (RKW/BW), and aortic weight to the length of the aorta (AW/length) were calculated [15][16][17] .…”

G.ALPHA.q-Protein Carboxyl Terminus Imitation Polypeptide GCIP-27 Attenuates Proliferation of Vascular Smooth Muscle Cells and Vascular Remodeling in Spontaneously Hypertensive Rats

“…11) GCIP-27, the optimized form of GCIP, could prevent hypertrophic responses in cultured rat cardiomyocytes induced by NA or Ang II, inhibited left ventricular hypertrophy induced by NA in mice and rats and that induced by suprarenal abdominal aortic stenosis in rats, as well as right ventricular hypertrophy induced by monocrotaline. [12][13][14] However, little is known about the effect of GCIP-27 on vascular remodeling. Because the pathophysiological process of vascular remodeling is quite complex and may include unique elements not observed in cardiac hypertrophy, it is necessary to characterize the effect of GCIP-27 on vascular remodeling.…”