Myocardial fibrosis in transforming growth factor β1 heterozygous mice
Myocardial fibrosis in transforming growth factor β1 heterozygous mice
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DOI：
10.1006/jmcc.1999.1065
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发表时间：
2000-02-01
影响因子：
5
通讯作者：
Conrad, CH
中科院分区：
文献类型：
--
作者：
Brooks, WW;Conrad, CH
衰老与心肌细胞外基质成分增加和收缩功能障碍有关。转化生长因子-β(1)已被证明调节心脏胶原基因的表达和细胞外基质成分的合成，并可能参与随着年龄的增长而增加的心肌纤维化。因此，我们研究了转化生长因子-β(1)杂合突变小鼠-是否会比正常小鼠表现出更少的与年龄相关的心肌纤维化。对12只杂合的转化生长因子-β(+/-)缺陷小鼠和26只野生型对照进行了检测，以确定是否存在因缺失一个转化生长因子-β(1)等位基因而导致的24个月龄心肌纤维化的发生或死亡率的差异。存活到24月龄的动物被处死，并在分离的灌流心脏和6月龄对照组小鼠的心脏中进行了形态和功能研究。在等容(LV中为球囊)的朗宁多夫制剂中评估LV的压力-体积关系。12只转化生长因子-β(1)缺陷小鼠中有11只(92%)存活到24月龄，而年龄匹配的对照组小鼠存活率为66%(12/18)(P
Aging is associated with an increase in myocardial extracellular matrix components and contractile dysfunction. Transforming growth factor-beta(1) (TGF-beta(1)) has been shown to regulate expression of collagen genes and extracellular matrix component synthesis in the heart, and may contribute to the increase in myocardial fibrosis with aging. Therefore, we examined whether TGF-beta(1) heterozygous mutant mice-would exhibit less age-associated myocardial fibrosis than normal mice. Twelve heterozygous TGF-beta (+/-) deficient mice and 26 wild-type controls were examined to determine if there was a difference in development of myocardial fibrosis or mortality at 24 months of age due to the loss of one TGF-beta(1) allele. Animals which survived to 24 months of age were killed, and morphometric and functional studies were performed in isolated perfused hearts and in hearts from 6 month old control mice. Pressure-volume relations of the LV were assessed in the isovolumic (balloon in LV) Langendorff preparation. Eleven of 12 (92%) TGF-beta(1) deficient mice survived to 24 months of age in comparison to 66% (12/18) age-matched controls (P