Sakamoto Aiji
Division of Biotechnology, National Cardiovascular Center Research Institute, Osaka, and Form and Function, PRESTO, Japan Science and Technology Agency, Saitama, Japan.
Exp Clin Cardiol. 2003 Fall;8(3):143-6.
Cardiomyopathy (CM) is a life-threatening disease with progressive degeneration of cardiac muscle. From a representative animal model of CM, the BIO14.6 hamster, arose the TO-2 strain manifesting a severe, dilated form of CM. Previous studies demonstrated that both strains have an identical genomic deletion disrupting the delta-sarcoglycan gene to cause CM.
To elucidate an additional pathogenesis for cardiac dilation in the TO-2 hamster.
Reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the expression levels of genes for cardiac hypertrophy, such as beta-myosin heavy chain and preproendothelin-1. The involvement of apoptosis in CM was tested using terminal deoxynucleotidyl transferase-mediated dUTP-biotin end-labelling (TUNEL) and DNA ladder assays. The progression of cardiac degeneration was visualized using specific histological staining techniques. Echocardiography was performed to estimate the wall thickness and the movement of a living hamster heart.
RT-PCR showed the expression of the genes involved in cardiac hypertrophy to be higher in TO-2 hamsters than in BIO14.6 hamsters, contary to what the thin myocardium may suggest. DNA ladder and TUNEL assays showed no significant difference in apoptosis in the hearts of either strain. In contrast, the infiltrate of inflammatory cells was prominent in the myocardium of TO-2 hamsters. In addition to dilation of the cardiac chamber, echocardiography also revealed disharmonized contraction in TO-2 hearts without apparent arrhythmias.
Impairment of compensatory cardiac hypertrophy or involvement of apoptosis is less likely to be an additional pathogenesis in the TO-2 hamster. The present data suggest that augmented necrosis is the principal cause of severe CM in the TO-2 hamster. Further analysis of the molecular pathogenesis of TO-2 would help to disclose the final common pathways for the manifestation of CM.
心肌病（CM）是一种危及生命的疾病，其中心肌会进行性退化。从CM的代表性动物模型BIO14.6仓鼠中，产生了表现为严重扩张型CM的TO-2品系。先前的研究表明，这两个品系都有相同的基因组缺失，破坏了δ-肌聚糖基因，从而导致CM。
阐明TO-2仓鼠心脏扩张的另一种发病机制。
采用逆转录-聚合酶链反应（RT-PCR）评估心脏肥大相关基因的表达水平，如β-肌球蛋白重链和前内皮素原-1。使用末端脱氧核苷酸转移酶介导的dUTP-生物素末端标记（TUNEL）和DNA梯状条带分析检测凋亡在CM中的作用。使用特定的组织学染色技术观察心脏退化的进展。进行超声心动图检查以评估活体仓鼠心脏的壁厚和运动情况。
RT-PCR显示，与薄心肌可能提示的情况相反，TO-2仓鼠中参与心脏肥大的基因表达高于BIO14.6仓鼠。DNA梯状条带和TUNEL分析显示，两种品系心脏中的凋亡无显著差异。相比之下，TO-2仓鼠心肌中的炎性细胞浸润较为明显。除了心腔扩张外，超声心动图还显示TO-2心脏收缩不协调，但无明显心律失常。
代偿性心脏肥大受损或凋亡参与不太可能是TO-2仓鼠的另一种发病机制。目前的数据表明，坏死增加是TO-2仓鼠严重CM的主要原因。对TO-2分子发病机制的进一步分析将有助于揭示CM表现的最终共同途径。
