REGULATION OF PROCOLLAGEN METABOLISM IN THE PRESSURE-OVERLOADED RAT-HEART
REGULATION OF PROCOLLAGEN METABOLISM IN THE PRESSURE-OVERLOADED RAT-HEART
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DOI：
10.1172/jci116270
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发表时间：
1993-03-01
影响因子：
15.9
通讯作者：
SAMAREL, AM
中科院分区：
文献类型：
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作者：
ELEFTHERIADES, EG;DURAND, JB;SAMAREL, AM
为了确定持续高血压期间心肌纤维胶原不成比例积聚的分子事件，我们检测了幼大鼠腹主动脉结扎后1-16周体内前胶原合成、胶原积聚和细胞内前胶原降解的速率。这些测量值与I型和III型前胶原多肽的组织mRNA水平相关。带状动物出现中度、持续性高血压和轻度左心室肥大。III型前胶原mRNA水平的增加被检测到后带早期，并持续整个观察期。在高血压诱导后1周内观察到不成比例的胶原积聚，但无纤维化的组织学证据。在这个时间点，原纤维胶原蛋白的积累并不是由于前胶原合成的大量增加，而是细胞内前胶原降解速率的显著降低。间质纤维化，但是，观察16周后捆绑。I型前胶原mRNA水平增加6倍，但仅在16周的高血压。这些结果与16周时的体内前胶原合成实验结果相关良好，该实验表明左心室前胶原生物合成增加了三倍。我们的结论是，翻译前以及翻译后机制调节纤维胶原蛋白沉积在心肌细胞外基质在持续高血压。
To determine the molecular events responsible for the disproportionate accumulation of myocardial fibrillar collagens during sustained hypertension, we examined the in vivo rate of procollagen synthesis, collagen accumulation, and intracellular procollagen degradation 1-16 wk after abdominal aortic banding in young rats. These measurements were correlated with tissue mRNA levels for type I and type III procollagen polypeptides. Banded animals developed moderate, sustained hypertension and mild left ventricular hypertrophy. Increased type III procollagen mRNA levels were detected early after banding and persisted for the entire observation period. Disproportionate collagen accumulation without histological evidence of fibrosis was noted within 1 wk after hypertension induction. Fibrillar collagen accumulation at this time point resulted not from a major increase in procollagen synthesis, but rather a marked decrease in the rate of intracellular procollagen degradation. Interstitial fibrosis, however, was observed 16 wk after banding. Type I procollagen mRNA levels were increased six-fold, but only after 16 wk of hypertension. These results correlated well with the results of in vivo procollagen synthesis experiments at 16 wk, which demonstrated a threefold increase in left ventricular procollagen biosynthesis. We conclude that pretranslational as well as posttranslational mechanisms regulate fibrillar collagen deposition in the myocardial extracellular matrix during sustained hypertension.