INCREASED COLLAGEN-SYNTHESIS AND DECREASED COLLAGEN DEGRADATION IN RIGHT-VENTRICULAR HYPERTROPHY INDUCED BY PRESSURE-OVERLOAD

Objective: The aim was to examine the effect of pressure overload in rabbits on ventricular collagen metabolism and procollagen gene expression. Methods: Right ventricular hypertrophy was induced by banding the pulmonary artery such that the diameter of the vessel was reduced by 50%, and animals killed in groups after two and 14 days. Collagen synthesis and degradation of newly synthesised collagen were assessed following a single intravenous injection of H-3-proline with a flooding dose of non-radioactive proline, given 3 h before the animals were killed. Northern and slot blot analyses were performed to measure procollagen alpha(1) (I) mRNA. Results: The fractional collagen synthesis rate increased sixfold in the right ventricle only 2 d after pulmonary artery banding (p < 0.001), then fell to just over double the control value by 14 d (p < 0.05 from control). The proportion of newly synthesised collagen degraded decreased from 50.7(SD 12.8)% to 26.8(15.8)% in 2 d (p < 0.05) and remained at this level. The procollagen alpha(1) (I) mRNA level increased by more than fourfold in the right ventricle 2 d after the onset of pressure overload, and was less than three times control levels at 14 d. Conclusions: The development of right ventricular hypertrophy is associated with a rapid increase in collagen production, with regulation at multiple sites in the biosynthetic pathway. This regulation occurs at both transcriptional and post translational levels.