Sex dimorphisms of crossbridge cycling kinetics in transgenic hypertrophic cardiomyopathy mice
Sex dimorphisms of crossbridge cycling kinetics in transgenic hypertrophic cardiomyopathy mice
复制标题
DOI：
10.1152/ajpheart.00592.2015
复制
发表时间：
2016-07-01
影响因子：
4.8
通讯作者：
Konhilas, John P.
中科院分区：
文献类型：
--
作者：
Birch, Camille L.;Behunin, Samantha M.;Konhilas, John P.
家族性肥厚性心肌病（HCM）是肉眼的一种疾病，可能导致肥厚，扩张，限制性和/或心律不齐的心肌病，充血性心力衰竭或心脏突然死亡。我们假设来自具有突变体肌球蛋白重链的转基因HCM小鼠的心脏以性别特定的方式增加了收缩成本。为此，我们在早期（2 mo of Ege of Ege of of of of of of of的男性和女性野生型（WT）中评估了来自男性和女性野生型（WT）和HCM心脏的伸缩心脏小梁的张力和越野动力学的Ca2+敏感性。我们发现性别对Ca2+敏感性的显着影响，因此与WT对应物相比，HCM小鼠的雄性HCM小鼠表现出Ca2+敏感性的降低。 HCM转基因和性别通过ATPase-stemense关系的快速释放权限方案和张力成本显着影响力重建速率。在这些措施中，HCM雄性小径与WT对应物相比，雄性小径均表现出功能。此外，通过超声心动图，组织学，形态学和翻译后修饰测量的心脏重塑表明性别和HCM特异性作用。总之，雌性和雄性HCM小鼠在形态学，组织学和细胞水平上表现出性别二态杂交桥动力学以及性别依赖性心脏重塑。
Familial hypertrophic cardiomyopathy (HCM) is a disease of the sarcomere and may lead to hypertrophic, dilated, restrictive, and/or arrhythmogenic cardiomyopathy, congestive heart failure, or sudden cardiac death. We hypothesized that hearts from transgenic HCM mice harboring a mutant myosin heavy chain increase the energetic cost of contraction in a sex-specific manner. To do this, we assessed Ca2+ sensitivity of tension and crossbridge kinetics in demembranated cardiac trabeculas from male and female wild-type (WT) and HCM hearts at an early time point (2 mo of age). We found a significant effect of sex on Ca2+ sensitivity such that male, but not female, HCM mice displayed a decrease in Ca2+ sensitivity compared with WT counterparts. The HCM transgene and sex significantly impacted the rate of force redevelopment by a rapid release-restretch protocol and tension cost by the ATPase-tension relationship. In each of these measures, HCM male trabeculas displayed a gain-of-function when compared with WT counterparts. In addition, cardiac remodeling measured by echocardiography, histology, morphometry, and post-translational modifications demonstrated sex-and HCM-specific effects. In conclusion, female and male HCM mice display sex dimorphic crossbridge kinetics accompanied by sex-and HCM-dependent cardiac remodeling at the morphometric, histological, and cellular level.