Aging blunts NFκB activation and HSP expression in response to estrogen in isolated female rat cardiomyocytes

Abstract

ObjectiveWe investigated the role of aging vs. estrogen loss on the cardioprotective heat shock protein (HSP) response in a rat model. We hypothesized that aging itself would lead to a blunted HSP response, while 17β‐estradiol (E2) replacement in aging rats would confer protection against cellular injury through restoration of the HSP response.MethodsCardiomyocytes were isolated from ovariectomized adult (5 mos.) and aged (22 mos.) rats with and without 9 weeks of E2 replacement forming four groups: adult ovx, adult op, aged ovx, and aged op. Myocytes were treated in culture with E2 (5nM and 100nM) and analyzed for NFκB activation at 15 minutes and HSP expression at 12 h. Some cells were subjected to 6 hours of hypoxic injury followed by 24 hours of reoxygenation (H/R).Results100nM E2 activated NFκB and increased HSP 72 and 90 expression in adult ovx and adult op (p<0.05), while both aged ovx and aged op show no changes in response to E2. Levels of HSP 27, heme oxygenase‐1, and estrogen receptor (ER) did not did not differ among groups or after E2 treatment. All groups had increased LDH release in response to H/R injury; however, aged ovx had higher LDH release before and after H/R compared to all other groups.ConclusionsAging leads to a loss of NFκB activation and HSP expression in response to E2 and this is not due to a change in ER expression.Supported by the American Heart Association Western States Affiliate (JPS), the NIA AG019327 (AAK), and the Department of Veterans Affairs (AAK)