Rücker-Martin Catherine, Pecker Françoise, Godreau David, Hatem Stéphane N
CNRS ESA 8078, Physiologie Cardiovasculaire et Thymique, Hôpital Marie Lannelongue, 133 avenue de la Résistance, 92350 Le Plessis Robinson, France.
Cardiovasc Res. 2002 Jul;55(1):38-52. doi: 10.1016/s0008-6363(02)00338-3.
Severe myocyte alterations, characterized by enlarged myocytes and myolysis, is observed in fibrillating and dilated atria and contributes to atrial fibrillation. The aim of this study was to determine the nature of this cellular remodeling process and factors involved in its regulation.
In vivo, contractile proteins were studied in 24 human right atrial specimens by means of immunohistochemical techniques. In an attempt to reproduce in vitro the myocyte remodeling and to study its regulation, human atrial myocytes were cultured (n=27) and analyzed immunocytochemically; intracellular Ca(2+) transients (Ca(i)-tr) in response to electrical stimulation were monitored using Fura-2/AM.
In diseased specimens, sarcomeres, seen at the periphery of myolytic myocytes, stained positively with antibodies against sarcomeric proteins of the Z-band (alpha-actinin and titin epitope T12) but not with antibodies against titin epitope T11 (I-band) or desmin (intermediate filament). beta-myosin heavy chain (MHC) and smooth muscle alpha-actin, two proteins of the fetal program, were re-expressed. In culture, diseased myocytes also showed myolysis and glycogen accumulation; their sarcomeres stained positively with anti-alpha-actinin, anti-T12, anti-beta-MHC and anti-smooth muscle alpha-actin but not with anti-titin T11 or anti-desmin antibodies. At confluence, myocytes regained a normal sarcomeric apparatus and were excitable, as shown by electrical Ca(i)-tr triggering. This redifferentiation process was inhibited by fibroblast proliferation.
In diseased atria, myolytic myocytes are in a dedifferentiated state resembling that of immature muscle cells. In vitro, fibroblast proliferation prevents the reversibility of this cellular alteration.
在颤动和扩张的心房中可观察到严重的心肌细胞改变，其特征为心肌细胞增大和肌溶解，这是心房颤动发生的原因之一，本研究旨在确定这种细胞重塑过程的本质及其调节因素。
在体内，通过免疫组化技术对24份人类右心房标本中的收缩蛋白进行研究。为了在体外重现心肌细胞重塑并研究其调节机制，培养了人类心房肌细胞（n = 27）并进行免疫细胞化学分析；使用Fura-2/AM监测电刺激后细胞内Ca(2+)瞬变（Ca(i)-tr）。
在患病标本中，在发生肌溶解的心肌细胞周边可见肌节，用抗Z带肌节蛋白（α-辅肌动蛋白和肌联蛋白表位T12）的抗体染色呈阳性，但用抗肌联蛋白表位T11（I带）或结蛋白（中间丝）的抗体染色呈阴性。β-肌球蛋白重链（MHC）和平滑肌α-肌动蛋白这两种胎儿期程序蛋白重新表达。在培养过程中，患病心肌细胞也表现出肌溶解和糖原积累；它们的肌节用抗α-辅肌动蛋白、抗T12、抗β-MHC和平滑肌α-肌动蛋白抗体染色呈阳性，但用抗肌联蛋白T11或抗结蛋白抗体染色呈阴性。汇合时，心肌细胞恢复了正常的肌节结构并具有兴奋性，电刺激引发的Ca(i)-tr显示了这一点。这种再分化过程受到成纤维细胞增殖的抑制。
在患病心房中，发生肌溶解的心肌细胞处于类似于未成熟肌细胞的去分化状态。在体外，成纤维细胞增殖阻止了这种细胞改变的可逆性。
