Pathogenesis of diverse clinical and pathological phenotypes in hypertrophic cardiomyopathy
Pathogenesis of diverse clinical and pathological phenotypes in hypertrophic cardiomyopathy
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DOI：
10.1016/s0140-6736(99)06187-5
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发表时间：
2000-01-01
期刊：
影响因子：
168.9
通讯作者：
Marian, AJ
中科院分区：
文献类型：
--
作者：
Marian, AJ
一般认为肥厚型心肌病的心肌收缩力增加。我提出相反的观点，即在这种疾病中心肌细胞收缩力降低。因此，收缩缺陷为心脏中营养因子的表达增加提供了主要刺激，这导致肥大、间质纤维化和其他表型。个体间营养因子表达的差异可以解释表型的变异性。心肌细胞的基因转移研究显示肥厚型心肌病患者心肌收缩力受损和营养因子表达增加支持这一假设。检验这一假设需要测量从肥厚型心肌病患者中分离的心肌细胞的收缩性，鉴定这些患者心脏中的主要营养因子，并研究其抑制是否可以预防或导致心脏表型的消退。
Myocardial contractility is generally believed to be increased in hypertrophic cardiomyopathy. I propose the opposite-that cardiac myocyte contractility Is decreased in this disorder. Accordingly, the contractile deficit provides the primary stimulus for increased expression of trophic factors in the heart, which leads to hypertrophy, interstitial fibrosis, and other phenotypes. Variation among individuals in expression of trophic factors would account for the variability of phenotypes. Gene transfer studies in cardiac myocytes showing impaired contractility and increased expression of trophic factors in the myocardium of patients with hypertrophic cardiomyopathy support this hypothesis. Testing of the hypothesis would require measurement of contractility of cardiac myocytes isolated from patients with hypertrophic cardiomyopathy, identification of the main trophic factors in the hearts of these patients, and investigation of whether their inhibition can prevent or lead to regression of the cardiac phenotypes.