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Dr Anna Walaszczyk: Therapeutic potential of Navitoclax in age-related cardiovascular diseases
Cardiovascular disease (CVD) is the leading cause of death in individuals over 60 years old. Aging is associated with an increased prevalence of coronary artery disease and a poorer prognosis following of acute myocardial infarction (MI). We have demonstrated that oxidative stress induces myocardial senescence, which is a major contributor to impaired function. In aged mice, prophylactic treatment with the senolytics drug navitoclax reduces senescence and the expression of SASP associated proteins resulting in attenuated age-related myocardial remodelling and improved survival and functional outcome following MI. In young animals, navitoclax treatment following MI with reperfusion improved left ventricular function, increased myocardial vascularization, and decreased scar size. SWATH-MS based proteomics revealed that elimination of senescent cells attenuated biological processes associated with maladaptive remodelling including fibrosis and inflammation. Cytokine array demonstrated navitoclax reduced expression of proinflammatory, profibrotic and anti-angiogenic cytokines, including interferon gamma-induced protein-10, TGF-β3, interleukin-11, interleukin-16 and fractalkine. Together our studies provide proof-of-concept evidence that cellular senescence and the proinflammatory SASP contribute to impaired heart function in multiple CVDs by promoting myocardial remodelling. Subsequently, senolytic treatment represents

Dec 11, 2020 02:30 PM in Warsaw

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