Calcification of myocardial necrosis is common in mice
Calcification of myocardial necrosis is common in mice
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DOI：
10.1007/s00428-005-0071-7
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发表时间：
2006-05-01
期刊：
影响因子：
3.5
通讯作者：
Ivandic, Boris Tomislav
中科院分区：
文献类型：
--
作者：
Korff, Susanne;Riechert, Nora;Ivandic, Boris Tomislav
独立于严重程度，心肌梗死的表型和临床结果可能在患者中有很大差异，这表明对愈合和适应过程有很强的遗传影响。由于对这些遗传决定因素知之甚少，我们研究了7种近交系小鼠对心肌损伤的组织反应，包括用于基因靶向或转基因过表达的小鼠。在C57 BL/6、C3 H/He、DBA/2、BALB/c、129 S1、FVB/n和A/J中，心肌坏死由非缺血性的、跨膜的冻融损伤产生。损伤后两天，在C3 H/He、DBA/2、BALB/c和129 S1中，坏死的心肌细胞钙化，这一表型称为营养不良性心脏钙质沉着症（DCC）。129 S1对DCC的敏感性由7号染色体上的一个位点Dyscalc 1决定，该位点先前在C3 H/He和DBA/2中鉴定。在冠状动脉结扎后的C3 H/He中也观察到DCC，表明DCC与损伤方式无关。相反，菌株C57 BL/6、FVB和A/J对DCC具有抗性，显示形成纤维性瘢痕而无钙化。在C3 H/He和C5713 L/6中详细研究了DCC的发展。在这两种菌株中，没有钙沉积，只有很少的结构解体，注意到在损伤后24小时的坏死心肌钙敏感的荧光染色。超微结构检查发现钙化的线粒体在C3 H/He，可能后来作为一个病灶的心肌细胞内快速钙化。我们的结论是，心肌坏死钙化的易感性可能是常见的近交系，应被视为一个强大的实验性心肌损伤的遗传修饰。
Independent of the severity, phenotypes and clinical outcomes of myocardial infarction may vary considerably in patients, suggesting a strong genetic influence on healing and adaptive processes. Since little is known about these genetic determinants, we examined the tissue response to myocardial injury in seven inbred mouse strains, including those employed for gene targeting or transgenic overexpression. Myocardial necrosis was produced by nonischemic, trans-diaphragmal freeze-thaw injury in strains C57BL/6, C3H/He, DBA/2, BALB/c, 129S1, FVB/n and A/J. Two days after injury, necrotic cardiomyocytes calcified in C3H/He, DBA/2, BALB/c and 129S1, a phenotype known as dystrophic cardiac calcinosis (DCC). The susceptibility to DCC of 129S1 was determined by Dyscalc1, a locus on chromosome 7, which was identified previously in C3H/He and DBA/2. DCC was also observed in C3H/He following ischemic injury by permanent coronary artery ligation, indicating that DCC was independent of the mode of injury. In contrast, strains C57BL/6, FVB and A/J were resistant to DCC, showing formation of a fibrous scar without calcification. The development of DCC was studied in detail in C3H/He and C5713L/6. In both strains, no calcium deposition and only little structural disintegration were noted in necrotic myocardium 24 h after injury upon calcium-sensitive fluorescence staining. Ultrastructural examination revealed calcified mitochondria in C3H/He that may have served later as a nidus for rapid intracellular calcification of cardiomyocytes. We concluded that the susceptibility to calcification of myocardial necrosis may be common among inbred strains and should be recognised as a strong genetic modifier of experimental myocardial injury.