Yasojima K, Schwab C, McGeer E G, McGeer P L
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada.
Circ Res. 1998 Oct 19;83(8):860-9. doi: 10.1161/01.res.83.8.860.
In human heart, we detected mRNAs and proteins for C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9 with the use of reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemical techniques. We found an upregulation of both mRNAs and proteins in areas of recent and old myocardial infarctions. In both situations, the classical complement pathway was activated, with C4d, C3d, and the membrane attack complex (C5b-9) being deposited on damaged cardiac myocytes. These activated complement components were also identified on Western blots of infarcted tissue. Complement mRNAs in infarcted heart tissue were higher than those in liver, and liver complement mRNAs were not upregulated in cases with infarcted hearts. Our results establish that (1) complement proteins are endogenously produced by human heart; (2) the classical complement pathway is fully activated after myocardial infarction; (3) complement activation is directly involved in myocardial damage after ischemic insults; and (4) damage from complement activation may be chronically sustained. These data suggest that inhibition of the complement system should be effective in treating myocardial infarction.
在人类心脏中，我们利用逆转录聚合酶链反应、蛋白质免疫印迹法和免疫组织化学技术检测到了C1q、C1r、C1s、C2、C3、C4、C5、C6、C7、C8和C9的信使核糖核酸（mRNA）和蛋白质。我们发现，在近期和陈旧性心肌梗死区域，mRNA和蛋白质均上调。在这两种情况下，经典补体途径均被激活，C4d、C3d和膜攻击复合物（C5b-9）沉积在受损的心肌细胞上。在梗死组织的蛋白质免疫印迹中也鉴定出了这些激活的补体成分。梗死心脏组织中的补体mRNA高于肝脏中的补体mRNA，并且在心脏梗死病例中肝脏补体mRNA并未上调。我们的结果证实：（1）补体蛋白由人类心脏内源性产生；（2）心肌梗死后经典补体途径被完全激活；（3）补体激活直接参与缺血性损伤后的心肌损伤；（4）补体激活造成的损伤可能会长期持续。这些数据表明，抑制补体系统对治疗心肌梗死可能有效。
