Age and sex differences in vascular responsiveness in healthy and trauma patients: contribution of estrogen receptor-mediated Rho kinase and PKC pathways
Age and sex differences in vascular responsiveness in healthy and trauma patients: contribution of estrogen receptor-mediated Rho kinase and PKC pathways
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DOI：
10.1152/ajpheart.00645.2013
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发表时间：
2014-04-01
影响因子：
4.8
通讯作者：
Liu, Liangming
中科院分区：
文献类型：
--
作者：
Li, Tao;Xiao, Xudong;Liu, Liangming
有几种疾病表现出基于年龄和性别的差异。创伤性休克在血管反应性方面是否表现出这样的差异尚不清楚。在177名健康受试者和842名创伤患者(21-82岁)以及不同年龄(4、8、10、14、18和24周；1和1.5岁)和性别的正常和创伤性休克大鼠中，研究了血管反应性的年龄和性别差异及其可能的机制。中青年女性和育龄雌性大鼠在正常状态下血管反应性较高，创伤性休克后血管反应性下降较同年龄段男性和雄性大鼠低。外源性补充17β-雌二醇增加了8-24周雄性和雌性大鼠的血管反应性，并保留了创伤性休克大鼠的血管反应性。在1到1.5岁的大鼠中没有观察到任何效果。雌激素的这些保护作用与G蛋白偶联受体(GPR)30、雌激素受体介导的Rho激酶和PKC通路的激活密切相关。血管反应性在健康受试者和创伤患者中表现出基于年龄和性别的差异。雌激素及其受体(GPR30)通过基因组和非基因组机制介导Rho激酶和PKC的激活，从而在血管反应性中产生保护作用。这一发现对于几种涉及雌激素的与年龄和性别相关的疾病的个性化治疗非常重要。
Several medical conditions exhibit age-and sex-based differences. Whether or not traumatic shock exhibits such differences with regard to vascular responsiveness is not clear. In a cohort of 177 healthy subjects and 842 trauma patients (21-82 years) as well as different ages (4, 8, 10, 14, 18, and 24 wk; 1 and 1.5 years) and sexes of Sprague-Dawley normal and traumatic shock rats, the age-and sex-based differences of vascular responsiveness and the underlying mechanisms were investigated. Middle-aged and young women as well as female rats of reproductive age had higher vascular responsiveness in the normal condition and a lower decrease in vascular responsiveness after traumatic shock than older men and male rats of identical age. Exogenous supplementation of 17 beta-estrdiol increased vascular reactivity in both male and femal rats of 8-24 wk and preserved vascular responsiveness in rats following traumatic shock. No effect was observed in rats 1 to 1.5 years. These protective effects of estrogen were closely related to G protein-coupled receptor (GPR) 30, estrogen receptor-mediated Rho kinase, and PKC pathway activation. Vascular responsiveness exhibits age-and sex-based differences in healthy subjects and trauma patients. Estrogen and its receptor (GPR30) mediated activation of Rho kinase and PKC using genomic and nongenomic mechanisms to elicit protective effects in vascular responsiveness. This finding is important for the personalized treatment for several age-and sex-related diseases involving estrogen.