End-stage cardiac failure in humans is coupled with the induction of proliferating cell nuclear antigen and nuclear mitotic division in ventricular myocytes.
End-stage cardiac failure in humans is coupled with the induction of proliferating cell nuclear antigen and nuclear mitotic division in ventricular myocytes.
复制标题
人类的终末期心力衰竭与心室肌细胞中增殖细胞核抗原和核有丝分裂的诱导有关。
DOI：
10.1161/01.res.75.6.1050
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发表时间：
1994
影响因子：
20.1
通讯作者：
Anversa,P
中科院分区：
文献类型：
--
作者：
Quaini,F;Cigola,E;Lagrasta,C;Saccani,G;Quaini,E;Rossi,C;Olivetti,G;Anversa,P
增殖细胞核抗原（PCNA）是一种晚期生长调节基因，表达于细胞周期的G1-S边界，是DNA合成和细胞增殖所必需的。由于定量结果表明，心肌细胞增生发生在失代偿的人的心脏，我们推测，PCNA基因的诱导可能存在于人类的心脏衰竭。在充血性心力衰竭患者的左、右心室心肌标本中检测到PCNA蛋白。将从供体受试者收集的肌内膜活检用作对照组织。用PCNA单克隆抗体和免疫过氧化物酶技术测定心室肌细胞核阳性染色百分率。α-肌节肌动蛋白抗体染色证实PCNA在肌细胞中的定位。PCNA标记存在于29的左心室肌细胞的32个心脏检查。在右心室中，29个样品中有24个显示阳性染色。在25例患者的亚组中，测量了PCNA标记的肌细胞核的百分比，发现占左心室肌细胞的49 +/- 22%。对21例患者的右心室进行了类似的分析，显示49 +/- 19%的肌细胞核显示PCNA蛋白。此外，记录了肌细胞中的有丝分裂像。对这一细胞过程的定量分析显示，慢性心力衰竭中每100万个细胞中有11个肌细胞核显示有丝分裂图像。心肌梗死后，每百万个细胞中有两个细胞显示有丝分裂，并且这种现象仅限于坏死组织附近的区域。对照组心肌未见PCNA标记或核分裂象。因此，弥漫性PCNA标记和心肌细胞有丝分裂存在于终末期衰竭的心脏中的观察结果强烈表明，成年心室肌细胞不是终末分化的细胞，并且心肌细胞增生可能构成患病心脏的生长储备机制。
Proliferating cell nuclear antigen (PCNA) is a late growth-regulated gene that is expressed at the G1-S boundary of the cell cycle and is required for DNA synthesis and cell proliferation. Since quantitative results suggest that myocyte hyperplasia occurs in the decompensated human heart, we postulated that induction of the PCNA gene may be present in the failing heart in humans. PCNA protein was detected in myocardial samples obtained from the left and right ventricles of patients with congestive heart failure. Endomyocardial biopsies collected from donor subjects were used as control tissue. The percentage of positively stained myocyte nuclei in the ventricles was established by using PCNA monoclonal antibody and the immunoperoxidase technique. The localization of PCNA in myocytes was confirmed by alpha-sarcomeric actin antibody staining. PCNA labeling was present in left ventricular myocytes of 29 of the 32 hearts examined. In the right ventricle, 24 of the 29 samples showed positive staining. In a subset of 25 patients, the percentage of PCNA-labeled myocyte nuclei was measured and found to constitute 49 +/- 22% of left ventricular myocytes. A similar analysis for the right ventricle, conducted in 21 patients, showed that 49 +/- 19% of the myocyte nuclei exhibited PCNA protein. In addition, mitotic figures in myocytes were documented. A quantitative analysis of this cellular process revealed that 11 myocyte nuclei per 1 million cells exhibited mitotic images in chronic heart failure. Immediately after myocardial infarction, two cells per million showed mitotic division, and this phenomenon was restricted to the region adjacent to the necrotic tissue. No PCNA labeling or nuclear mitotic images were detected in the ventricular myocardium of control subjects. Thus, the observation that diffuse PCNA labeling and myocyte mitotic division are present in hearts with end-stage failure strongly suggests that adult ventricular myocytes are not terminally differentiated cells and that myocyte cellular hyperplasia may constitute a growth reserve mechanism of the diseased heart.