American journal of physiology. Heart and circulatory physiology
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Am. J. Physiol. Heart Circ. Physiol. · Mar 2014
Resveratrol promotes endothelial cell wound healing under laminar shear stress through an estrogen receptor-α-dependent pathway.
Restenosis is an adverse outcome of angioplasty, characterized by vascular smooth muscle cell (VSMC) hyperplasia. However, therapies targeting VSMC proliferation delay re-endothelialization, increasing the risk of thrombosis. Resveratrol (RESV) inhibits restenosis and promotes re-endothelialization after arterial injury, but in vitro studies assessing RESV-mediated effects on endothelial cell growth contradict these findings. ⋯ Under laminar shear stress (LSS), RESV dramatically enhanced endothelial cell wound healing and increased both the activation of extracellular signal-regulated kinase (ERK) and endothelial cell proliferation. Under LSS, small interfering RNA against ER-α, but not endothelial nitric oxide synthase, abolished RESV-induced ERK activation, endothelial cell proliferation, and wound healing. Thus these studies suggest that the EC phenotype induced by LSS better models the prohealing effects of RESV and that RESV and LSS interact to promote an ER-α-dependent mitogenic effect in endothelial cells.
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Am. J. Physiol. Heart Circ. Physiol. · Mar 2014
Estrogen-provided cardiac protection following burn trauma is mediated through a reduction in mitochondria-derived DAMPs.
Mitochondria-derived danger-associated molecular patterns (DAMPs) play important roles in sterile inflammation after acute injuries. This study was designed to test the hypothesis that 17β-estradiol protects the heart via suppressing myocardial mitochondrial DAMPs after burn injury using an animal model. Sprague-Dawley rats were given a third-degree scald burn comprising 40% total body surface area (TBSA). 17β-Estradiol, 0.5 mg/kg, or control vehicle was administered subcutaneously 15 min following burn. ⋯ Estradiol's anti-inflammatory effect was demonstrated by reduction in systemic and cardiac cytokines (TNF-α, IL-1β, and IL-6), decrease in NF-κB activation, and attenuation of the expression of inflammasome component ASC in the heart of burned rats. Estradiol-provided cardiac protection was shown by reduction in myocardial injury marker troponin-I, amendment of heart morphology, and improvement of cardiac contractility after burn injury. Together, these data suggest that postburn administration of 17β-estradiol protects the heart via an effective control over the generation of mitochondrial DAMPs (mtROS, cytochrome c, and mtDNA) that incite cardiac apoptosis and inflammation.