Genetic determination of cartilaginous metaplasia in mouse aorta.
Genetic determination of cartilaginous metaplasia in mouse aorta.
复制标题
小鼠主动脉软骨化生的遗传测定。
DOI：
10.1161/01.atv.15.12.2265
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Lusis,AJ
中科院分区：
文献类型：
--
作者：
Qiao,JH;Fishbein,MC;Demer,LL;Lusis,AJ
钙化经常发生在人类的动脉粥样硬化斑块中，但导致这一病理特征的细胞和遗传因素尚不清楚。我们之前报道过近亲繁殖菌株的动脉钙化是由基因决定的，现在我们报道与表达II型胶原的动脉软骨细胞相关的软骨化生可能是这种钙化的基础。未钙化和钙化的软骨化生均常与主动脉粥样硬化病变和钙化共发生，近交系间主动脉软骨化生的发生存在明显的遗传差异。C57BL/6J（有主动脉软骨化生）与C3H/HeJ（无主动脉软骨化生）的遗传杂交分析显示为隐性遗传模式；因此，f1小鼠完全没有软骨化生，与C3H/HeJ亲本菌株相同。对F2cross和一组由亲本菌株C57BL/6J和C3H/HeJ衍生的重组自交系的分析表明，主基因效应表现为不完全外显性。在这些遗传杂交中，主动脉钙化的发生与软骨化生的发生相关，表明这些性状之间存在联系。最后，我们观察到apoE基因零突变的小鼠自发性动脉粥样硬化病变中广泛存在钙化的软骨化生，这表明软骨化生是动脉壁钙化与动脉粥样硬化斑块相关的潜在途径。
Calcification frequently occurs in atherosclerotic plaques in humans, but the cellular and genetic factors contributing to this pathological trait are unknown. We previously reported that the arterial calcification among inbred strains is genetically determined, and we now report that cartilaginous metaplasia, associated with the presence of arterial chondrocytes that express type II collagen, may underlie this calcification. Both uncalcified and calcified cartilaginous metaplasia were often colocalized with aortic atheromatous lesions and calcification, and clear genetic differences were observed in the occurrence of aortic cartilaginous metaplasia among inbred strains. Analysis of a genetic cross between strains C57BL/6J (exhibiting aortic cartilaginous metaplasia) and C3H/HeJ (no aortic cartilaginous metaplasia) revealed a recessive inheritance pattern; thus, F1mice were entirely devoid of cartilaginous metaplasia, in common with the C3H/HeJ parental strain. Analyses of an F2cross and a set of recombinant inbred strains derived from parental strains C57BL/6J and C3H/HeJ were consistent with a major gene effect exhibiting incomplete penetrance. The occurrence of aortic calcification was correlated with the occurrence of cartilaginous metaplasia in these genetic crosses, suggesting a link between the traits. Finally, we observed widespread calcified cartilaginous metaplasia within spontaneous atherosclerotic lesions in mice targeted for a null mutation in the apoE gene, suggesting that cartilaginous metaplasia is a potential pathway for artery wall calcification associated with the atherosclerotic plaque.