Xueping Zhou1,2, Bunyen Teng1,2, S J Mustafa1,2. 1. Department of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia, USA. 2. Center for Cardiovascular and Respiratory Sciences and West Virginia Clinical & Translational Science Institute, Morgantown, West Virginia, USA.
Abstract
OBJECTIVE: Sex plays an important role in the pathophysiology of cardiovascular diseases. This study aims to investigate how sex impacts on the coronary flow regulation during atherosclerosis. METHODS: ApoE KO mouse fed with western diet were used for atherosclerosis model. Coronary RH and flow response were measured using Langendorff-perfused isolated hearts. RESULTS: Coronary RH and A23187-induced NO-dependent flow increases were significantly reduced in female (by ~28% and 48%, respectively), but not in male atherosclerotic mice. However, SNP-induced coronary vasodilation remains intact in both sexes of ApoE KO mice. L-NAME (NOS inhibitor) reduced baseline flow and RH to a lesser extent in ApoE KO (by ~19% and 31%) vs. WT (~30% and 59%, respectively), and abolished the sex difference in RH. In contrast, SCH58261 (a selective A2A AR antagonist) reduced the baseline flow and RH to a greater extent in atherosclerotic mice, but did not affect the sex difference. Immunofluorescent staining of coronary arteries showed a similar A2A AR upregulation in both sexes of ApoE KO mice. CONCLUSIONS: Our results suggest that during atherosclerosis, female mice are more susceptible to NO-dependent endothelial dysfunction and the upregulation of A2A AR may serve as a compensatory mechanism to counteract the compromised endothelial function.
OBJECTIVE: Sex plays an important role in the pathophysiology of cardiovascular diseases. This study aims to investigate how sex impacts on the coronary flow regulation during atherosclerosis. METHODS:ApoE KO mouse fed with western diet were used for atherosclerosis model. Coronary RH and flow response were measured using Langendorff-perfused isolated hearts. RESULTS: Coronary RH and A23187-induced NO-dependent flow increases were significantly reduced in female (by ~28% and 48%, respectively), but not in male atheroscleroticmice. However, SNP-induced coronary vasodilation remains intact in both sexes of ApoE KO mice. L-NAME (NOS inhibitor) reduced baseline flow and RH to a lesser extent in ApoE KO (by ~19% and 31%) vs. WT (~30% and 59%, respectively), and abolished the sex difference in RH. In contrast, SCH58261 (a selective A2A AR antagonist) reduced the baseline flow and RH to a greater extent in atheroscleroticmice, but did not affect the sex difference. Immunofluorescent staining of coronary arteries showed a similar A2A AR upregulation in both sexes of ApoE KO mice. CONCLUSIONS: Our results suggest that during atherosclerosis, female mice are more susceptible to NO-dependent endothelial dysfunction and the upregulation of A2A AR may serve as a compensatory mechanism to counteract the compromised endothelial function.
Authors: T Minamino; M Kitakaze; Y Matsumura; K Nishida; Y Kato; K Hashimura; Y Matsu-Ura; H Funaya; H Sato; T Kuzuya; M Hori Journal: J Am Coll Cardiol Date: 1998-05 Impact factor: 24.094
Authors: Silvana S Meyrelles; Veronica A Peotta; Thiago M C Pereira; Elisardo C Vasquez Journal: Lipids Health Dis Date: 2011-11-14 Impact factor: 3.876