Sex Differences in Myocardial Histology, Gene Expression, and Myocardial Recovery in Recent-Onset Cardiomyopathy.
Sex Differences in Myocardial Histology, Gene Expression, and Myocardial Recovery in Recent-Onset Cardiomyopathy.
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新发心肌病心肌组织学、基因表达和心肌恢复的性别差异。
DOI：
10.1016/j.jchf.2023.08.008
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
McNamara,DennisM
中科院分区：
文献类型：
--
作者：
Koczo,Agnes;Rao,Anjali;Starling,RandallC;Cooper,LeslieT;Dec,GWilliam;Alexis,JeffreyD;Gorcsan,John;McTiernan,Charles;McNamara,DennisM
在现有的EMBs亚组（n= 20）中，与男性相比，几种促凋亡配体和受体在女性中的表达较低，包括TNFR 1（女性1.53%[IQR：1.45%-1.76%] vs男性1.91%[IQR：1.67%-2.17%]; P= 0.01），Fas受体（女性0.26%[IQR：0.23%-0.28%] vs男性0.13%[IQR：0.11%-0.24%]; P= 0.01），FLICE（女性0.12%[IQR：0.09%-0.15%] vs男性0.16%[IQR：0.13%-0.20%]; P= 0.039）。女性的TNF-a基因表达也较低，接近显著性（女性0.09%[IQR：0.07%-0.13%] vs男性0.13%[IQR：0.11%-0.15%]; P= 0.058）（图1）。这项研究发现，与男性相比，ROCM女性患者的纤维化程度较低，心脏组织中几种促凋亡因子（包括Fas配体、FLICE和TNFR 1）的基因表达相应较低。此外，女性在6个月时的LVEF明显更好，尽管体表面积的LVEF和LVEDD指数相似。有几种可能的机制可以解释这些性别差异。我们的研究没有显示症状持续时间或护理表现的差异。先前的研究表明，女性性激素（主要是雌激素）的主要作用是保护心肌免受损伤。雌激素对心肌细胞有多种保护作用，包括抑制血管紧张素II刺激的钙调神经磷酸酶活性，这通常会导致肥大，以及阻止SMAD 2和SMAD 3纤维化诱导基因转录。4此外，研究指出，在卵巢切除后的动物模型中，雌激素对心脏肥大和纤维化的保护作用的丧失可以通过外源性雌激素补充相对重现。5在我们的研究中观察EMB组织学和基因表达的性别差异，女性可能不太可能进展到细胞凋亡和不可逆的细胞损伤，因此可能更有可能在急性肌病后恢复心室功能。进一步研究探索哪些保护机制导致心肌细胞中促凋亡组织表达的相对减少，如在本研究和其他研究中所观察到的，可能有助于靶向保护途径。
Among the subgroup of available EMBs (n= 20), several proapoptotic ligands and receptors demonstrated lower expression in women when compared with men including TNFR1 (women 1.53%[IQR: 1.45%-1.76%] vs men 1.91%[IQR: 1.67%-2.17%]; P= 0.01), Fas receptor (women 0.26%[IQR: 0.23%-0.28%] vs men 0.13%[IQR: 0.11%-0.24%]; P= 0.01), FLICE (women 0.12%[IQR: 0.09%-0.15%] vs men 0.16%[IQR: 0.13%-0.20%]; P= 0.039). Women also had lower gene expression of TNF-a, which approached significance (women 0.09%[IQR: 0.07%-0.13%] vs men 0.13%[IQR: 0.11%-0.15%]; P= 0.058)(Figure 1). This study found that women with ROCM had less fibrosis and corresponding lower cardiac tissue gene expression of several proapoptotic factors including Fas ligand, FLICE, and TNFR1, as compared with their male counterparts. Further, women had significantly better LVEF at 6 months despite similar entry LVEF and LVEDD indexed for body surface area. There are several possible mechanisms that may explain these sex differences. Our study did not reveal differences in duration of symptoms or presentation to care. Prior studies have suggested a predominant role of female sex hormones, primarily estrogen, which protect against myocardial injury. Estrogen has multiple protective roles for the cardiomyocyte, including repression of angiotensin II–stimulated calcineurin activity that normally causes hypertrophy as well as preventing SMAD2 and SMAD3 fibrosis-inducing gene transcription. 4 Further, studies note that the loss of estrogen protection against cardiac hypertrophy and fibrosis in postovariectomized animal models can be relatively recapitulated with exogenous estrogen supplementation. 5 In looking at sex differences in EMB histology and gene expression in our study, women may be less likely to progress to apoptosis and irreversible cell injury and thus may be more likely to recover ventricular function after an acute myopathy. Further studies exploring which protective mechanisms lead to the relative decreases in proapoptotic tissue expression in cardiomyocytes as observed in this and other studies may help to target pathways for preservation.
影响因子：
6
作者：
Simon, Marc A.;Primack, Brian A.;Teuteberg, Jeffrey;Kormos, Robert L.;Bermudez, Christian;Toyoda, Yoshiya;Shah, Hemal;Gorcsan, John, III;McNamara, Dennis M.
通讯作者：
McNamara, Dennis M.
影响因子：
4.8
作者：
Pedram, Ali;Razandi, Mahnaz;Levin, Ellis R.
通讯作者：
Levin, Ellis R.
影响因子：
6
作者：
Boehmer, John P.;Starling, Randall C.;McNamara, Dennis M.
通讯作者：
McNamara, Dennis M.