Endothelial Senescence Contributes to Heart Failure With Preserved Ejection Fraction in an Aging Mouse Model

• DOI: 10.1161/circheartfailure.116.003806
• Publication Date: 2017-06-14T01:00:33Z
• Authors: Andreas B. Gevaert; Hadis Shakeri; Arthur J. Leloup; Cor E. Van Hove; Guido R.Y. De Meyer; Christiaan J. Vrints; Katrien Lemmens; Emeline M. Van Cr...
• Keywords: Senescence; Endothelial Dysfunction

Because of global aging, the prevalence heart failure with preserved ejection fraction (HFpEF) continues to rise. Although HFpEF pathophysiology remains incompletely understood, endothelial inflammation is stated play a central role. Cellular senescence process cellular growth arrest linked aging and inflammation. We used mice accelerated investigate role in development.Senescence-accelerated (SAM, n=18) control normal (n=15) were fed chow or high-fat, high-salt diet (WD). Vascular cardiac function was assessed at 8, 16, 24 weeks age. At weeks, both SAM on WD (SAM-WD) regular displayed dysfunction, as evidenced by impaired acetylcholine-induced relaxation aortic segments reduced basal nitric oxide. week 24, SAM-WD had developed HFpEF, characterized diastolic left ventricular hypertrophy, atrial dilatation, interstitial fibrosis. Also, exercise capacity lung weight increased. Cardiovascular immunohistochemical immunofluorescence staining hearts aortas. showed increased (intercellular adhesion molecule 1 expression) (acetyl-p53/CD31 costaining). The latter correlated intercellular expression.SAM develop dysfunction. Adding high-salt, high-fat accelerates instigates This coincides hemodynamic structural changes typical HFpEF. Targeting could be new therapeutic avenue