rapid changes in cardiac myofilament function following the acute activation of estrogen receptor-alpha心脏肌丝快速变化函数雌激素receptor-alpha急性激活后.pdfVIP

Rapid Changes in Cardiac Myofilament Function following the Acute Activation of Estrogen Receptor- Alpha 1 1 1,2 Justyna Kulpa , Nirmala Chinnappareddy , W. Glen Pyle * 1 Cardiovascular Research Group, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada, 2 Biophysics Interdepartmental Group, University of Guelph, Guelph, Ontario, Canada Abstract Estrogens have well-recognized and complex cardiovascular effects, including altering myocardial contractility through changes in myofilament function. The presence of multiple estrogen receptor (ER) isoforms in the heart may explain some discrepant findings about the cardiac effects of estrogens. Most studies examining the impact of estrogens on the heart have focused on chronic changes in estrogen levels, and have not investigated rapid, non-genomic pathways. The first objective of this study was to determine how acute activation of ERa impacts cardiac myofilaments. Nongenomic myocardial estrogen signaling is associated with the activation of a variety of signaling pathways. p38 MAPK has been implicated in acute ER signaling in the heart, and is known to affect myofilament function. Thus, the second objective of this study was to determine if acute ERa activation mediates its myofilament effects through p38 MAPK recruitment. Hearts from female C57Bl/6 mice were perfused with the ERa agonist PPT and myofilaments isolated. Activation of ERa depressed actomyosin MgATPase activity and decreased myofilament calcium sensitivity. Inhibition of p38 MAPK attenuated the myofilament effects of ERa activation. ERa stimulation did not affect global myof