Murakami M, Kusachi S, Nakahama M, Naito I, Murakami T, Doi M, Kondo J, Higashi T, Ninomiya Y, Tsuji T
First Department of Internal Medicine, Okayama University Medical School, Japan.
J Mol Cell Cardiol. 1998 Jun;30(6):1191-202. doi: 10.1006/jmcc.1998.0684.
Healing processes affect ventricular remodeling, an important prognostic factor in acute myocardial infarction (AMI). Type IV collagen, a major component of the basement membrane, has been demonstrated to appear in the infarct zone. Six type IV alpha chains, alpha 1 to alpha 6 [alpha 1(IV) to alpha 6(IV)], have been identified. We examined the expression of the alpha 1(IV), alpha 2(IV), alpha 3(IV) and alpha 5(IV) in experimental rat AMI induced by permanent ligation of the left coronary artery in male Sprague-Dawley rats. Neonatal cardiac fibroblasts cultured to reach confluency were also used to examine the hypoxic induction of the expression of these chains. Northern blotting, in situ hybridization, and immunohistochemical staining were employed to examine the alpha chain expression. With the in situ hybridization, alpha 1(IV) and alpha 2(IV) mRNA signals were observed in spindle-shaped mesenchymal cells in the intercellular spaces, in the vascular endothelial cells and in some myocytes in the normal myocardium. Signals for both alpha 1(IV) and alpha 2(IV) mRNA appeared in the spindle-shaped mesenchymal cells located between the surviving myocytes in the infarct peripheral zone at 24 h after the ligation. These signals extended into the central zone and reached the center point of the infarct 5 days after the ligation. Neither alpha 3(IV) nor alpha 5(IV) mRNA signals were observed in the infarct zone. Northern blotting demonstrated increased expressions of alpha 1(IV) and alpha 2(IV) mRNA in the infarct zone compared to the sham-operated hearts. The expression of alpha 5(IV) mRNA was weak in the sham-operated hearts but was not detected in the infarct zone. alpha 3(IV) mRNA was not expressed in the infarct zones or sham-operated hearts. In the cultured cardiac fibroblasts, a hypoxic induction of the expression of both alpha 1(IV) and alpha 2(IV) mRNA was demonstrated by Northern hybridization. Immunohistochemistry revealed alpha 1(IV) and alpha 2(IV) staining in the infarct lesion. The findings demonstrate that among the type IV collagen alpha chains examined, alpha 1(IV) and alpha 2(IV) produced by mesenchymal cells appeared in the infarct zone, suggesting that type IV collagen composed by alpha 1 and alpha 2 chains contributes to the pathological course of myocardial infarction.
愈合过程会影响心室重塑，这是急性心肌梗死（AMI）的一个重要预后因素。IV型胶原是基底膜的主要成分，已被证实在梗死区域出现。已鉴定出六种IV型α链，即α1至α6[α1(IV)至α6(IV)]。我们检测了雄性Sprague-Dawley大鼠永久性结扎左冠状动脉诱导的实验性大鼠AMI中α1(IV)、α2(IV)、α3(IV)和α5(IV)的表达。还使用培养至汇合的新生心脏成纤维细胞来检测这些链表达的缺氧诱导情况。采用Northern印迹法、原位杂交法和免疫组织化学染色法检测α链表达。通过原位杂交，在正常心肌的细胞间隙中的梭形间充质细胞、血管内皮细胞和一些心肌细胞中观察到α1(IV)和α2(IV) mRNA信号。结扎后24小时，α1(IV)和α2(IV) mRNA信号出现在梗死周边区存活心肌细胞之间的梭形间充质细胞中。这些信号在结扎后5天延伸至中央区并到达梗死中心点。在梗死区域未观察到α3(IV)和α5(IV) mRNA信号。Northern印迹法显示，与假手术心脏相比，梗死区域中α1(IV)和α2(IV) mRNA表达增加。α5(IV) mRNA在假手术心脏中的表达较弱，但在梗死区域未检测到。α3(IV) mRNA在梗死区域或假手术心脏中均未表达。在培养的心脏成纤维细胞中，Northern杂交显示α1(IV)和α2(IV) mRNA表达的缺氧诱导。免疫组织化学显示梗死病变中有α1(IV)和α2(IV)染色。研究结果表明，在所检测的IV型胶原α链中，间充质细胞产生的α1(IV)和α2(IV)出现在梗死区域，提示由α1和α2链组成的IV型胶原有助于心肌梗死的病理过程。
