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

INCREASED COLLAGEN-SYNTHESIS AND DECREASED COLLAGEN DEGRADATION IN RIGHT-VENTRICULAR HYPERTROPHY INDUCED BY PRESSURE-OVERLOAD
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DOI:
10.1093/cvr/28.10.1581
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发表时间:
1994-10-01
影响因子:
10.8
通讯作者:
STIREWALT, WS
STIREWALT, WS
中科院分区:
医学1区
文献类型:
--
作者:
BISHOP, JE;RHODES, S;STIREWALT, WS

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目的:探讨压力超负荷对兔心脏胶原代谢及前胶原基因表达的影响。方法:采用结扎大鼠肺动脉造成右室肥厚,使血管内径缩小50%,分别于术后2天和14天处死动物。动物处死前3h单次静脉注射H-3-Pro和一定剂量的非放射性Pro,观察胶原合成和新合成胶原的降解情况。Northern和Slot印迹分析检测前胶原α(1)(I)mRNA。结果:肺动脉结扎后仅2d,右室心肌胶原合成率增加6倍(p<0.001),14d时降至对照组的两倍多(p<0.05)。新合成的胶原降解比例在2d内从50.7(SD 12.8)%降至26.8(15.8)%(p<0.05),并维持在该水平。压力超负荷后2d,右室前胶原α(1)(I)mRNA水平增加4倍以上,14d时不到对照组的3倍。结论:右室肥厚的发生与胶原生成的快速增加有关,在生物合成途径中多部位参与调节。这种调节发生在转录和翻译后水平上。
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.