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 3H-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.
Bishop
J E
JE
Biochemistry Unit, National Heart and Lung Institute, London, United Kingdom.
Rhodes
S
S
Laurent
G J
GJ
Low
R B
RB
Stirewalt
W S
WS
D000818:Animals; D015152:Blotting, Northern; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006352:Heart Ventricles / Q000378:metabolism*; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism*; D008297:Male; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits
D011347:Procollagen; D012333:RNA, Messenger; D003094:Collagen