Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy
Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy
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DOI：
10.1016/s0735-1097(02)03009-7
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发表时间：
2003-05-21
影响因子：
24
通讯作者：
Watkins, H
中科院分区：
文献类型：
--
作者：
Crilley, JG;Boehm, EA;Watkins, H
我们研究了心脏能量学在三个不同的家族性肥厚型心肌病（HCM）疾病基因突变的主题，其中一些人是非渗透载体没有hypertrophy，使用磷-31磁共振spectroscopic.Background家族性肥厚型心肌病是由肌节蛋白基因突变。这些突变蛋白引起疾病的机制尚不确定。已经提出了肌细胞收缩性的缺陷，但随后在力产生的体外研究中显示了不同类型突变的相反结果。另一种假说的“能量妥协”的利用效率低下的三磷酸腺苷（ATP）的结果已被建议，但在体内的数据在人类与基因型HCM是lacked.METHODS心脏磷酸肌酸（PCr）ATP的比例确定在休息中的31例患者中，无论是β-肌球蛋白重链，心肌肌钙蛋白T，或肌球蛋白结合蛋白C的基因突变，并在24个控制。经胸超声心动图被用来测量左心室（LV）的尺寸和最大壁厚。结果PCr/ATP在HCM受试者减少了30%，相对于对照组（1.70 +/- 0.43 vs. 2.44 +/- 0.30; p < 0.001），并在所有三个疾病基因组的减少是一个类似的幅度。PCr/ATP同样减少受试者（n = 24）和没有（n = 7）LV hypertrophy.CONCLUSIONS我们的数据提供了证据的生物能量赤字基因型证实的HCM，这是目前在三个疾病基因组的相似程度。能量异常的存在，即使在那些没有肥大，支持心脏能量学改变和疾病表型的发展之间的联系。(C)2003年由美国心脏病学会基金会。
OBJECTIVES We investigated cardiac energetics in subjects with mutations in three different familial hypertrophic cardiomyopathy (HCM) disease genes, some of whom were nonpenetrant carriers without hypertrophy, using phosphorus-31 magnetic resonance spectroscopy.BACKGROUND Familial hypertrophic cardiomyopathy is caused by mutations in sarcomeric protein genes. The mechanism by which these mutant proteins cause disease is uncertain. A defect of myocyte contractility had been proposed, but in vitro studies of force generation have subsequently shown opposing results in different classes of mutation. An alternative hypothesis of "energy compromise" resulting from inefficient utilization of adenosine triphosphate (ATP) has been suggested, but in vivo data in humans with genotyped HCM are lacking.METHODS The cardiac phosphocreatine (PCr) to ATP ratio was determined at rest in 31 patients harboring mutations in the genes for either beta-myosin heavy chain, cardiac troponin T, or myosin-binding protein C, and in 24 controls. Transthoracic echocardiography was used to measure left ventricular (LV) dimensions and maximal wall thickness.RESULTS The PCr/ATP was reduced in the HCM subjects by 30% relative to controls (1.70 +/- 0.43 vs. 2.44 +/- 0.30; p < 0.001), and the reduction was of a similar magnitude in all three disease-gene groups. The PCr/ATP was equally reduced in subjects with (n = 24) and without (n = 7) LV hypertrophy.CONCLUSIONS Our data provide evidence of a bioenergetic deficit in genotype-confirmed HCM, which is present to a similar degree in three disease-gene groups. The presence of energetic abnormalities, even in those without hypertrophy, supports a proposed link between altered cardiac energetics and development of the disease phenotype. (C) 2003 by the American College of Cardiology Foundation.