Exposure to Stress Alters Cardiac Gene Expression and Exacerbates Myocardial Ischemic Injury in the Female Murine Heart.
Exposure to Stress Alters Cardiac Gene Expression and Exacerbates Myocardial Ischemic Injury in the Female Murine Heart.
复制标题
应激改变雌性小鼠心脏基因表达并加重心肌缺血损伤。
DOI：
10.3390/ijms241310994
复制
发表时间：
2023-07-01
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
精神压力是女性心肌梗死的危险因素。这项研究的中心假设是，束缚应激诱导心脏基因表达的性别特异性变化，这导致对缺血/再灌注损伤的反应增强，这是由于女性心脏中促氧化环境的发展。我们在束缚应激模型中挑战雄性和雌性C57 BL/6小鼠，以模仿精神应激的影响。暴露于束缚应激导致心脏肥大、炎症和铁依赖性细胞死亡（铁凋亡）相关基因表达的性别差异。在这些基因中，我们确定了肿瘤蛋白p53和细胞周期蛋白依赖性激酶抑制剂1A（p21），它们在铁凋亡中的作用存在争议。限制应激雌性动物对I/R损伤的反应加剧与p53和核因子红细胞2相关因子2（Nrf 2，抗氧化反应系统ARE的主要调节因子）的下调相关。S-女性心脏也表现出增加的超氧化物水平，脂质过氧化反应，并与他们的男性同行相比，胰高血糖素-内过氧化物合酶2（Ptgs 2）的表达（一个标志的ferroptosis）。我们的研究是第一个测试性别特异性的约束压力对心脏的影响，在设置I/R及其结果。
Mental stress is a risk factor for myocardial infarction in women. The central hypothesis of this study is that restraint stress induces sex-specific changes in gene expression in the heart, which leads to an intensified response to ischemia/reperfusion injury due to the development of a pro-oxidative environment in female hearts. We challenged male and female C57BL/6 mice in a restraint stress model to mimic the effects of mental stress. Exposure to restraint stress led to sex differences in the expression of genes involved in cardiac hypertrophy, inflammation, and iron-dependent cell death (ferroptosis). Among those genes, we identified tumor protein p53 and cyclin-dependent kinase inhibitor 1A (p21), which have established controversial roles in ferroptosis. The exacerbated response to I/R injury in restraint-stressed females correlated with downregulation of p53 and nuclear factor erythroid 2–related factor 2 (Nrf2, a master regulator of the antioxidant response system-ARE). S-female hearts also showed increased superoxide levels, lipid peroxidation, and prostaglandin-endoperoxide synthase 2 (Ptgs2) expression (a hallmark of ferroptosis) compared with those of their male counterparts. Our study is the first to test the sex-specific impact of restraint stress on the heart in the setting of I/R and its outcome.
登录
查看更多内容
肿瘤抑制蛋白 p53 和铁死亡网络
影响因子：
7.4
作者：
Kang R;Kroemer G;Tang D
通讯作者：
Tang D
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
20.1
作者：
Garcia M;Mulvagh SL;Merz CN;Buring JE;Manson JE
通讯作者：
Manson JE
DOI：
10.3791/1088
发表时间：
2008-12-22
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Komada, Munekazu;Takao, Keizo;Miyakawa, Tsuyoshi
通讯作者：
Miyakawa, Tsuyoshi
影响因子：
3.4
作者：
Li, Hong;Zou, Tong;Yang, Jie-Fu
通讯作者：
Yang, Jie-Fu