SIRT1 and Mitochondrial Homeostasis in Heart Failure

Presenter Information

Van Le, University of South Florida

Streaming Media

Mentor Information

Ji Li (College of Medicine Surgery)

Description

Sirtuin 1 (SIRT 1) is a nicotinamide adenine dinucleotide (NAD+) dependent histone deacetylase. SIRT 1 has a crucial role in mediating cell survival and protecting the heart from several stress, such as hypertrophy and prevent progressive cardiac failure. Recently, SIRT1 is emerged as a crucial regulator of mitochondrial function in heart, while the mitochondrial dysfunction has been implicated in the development of heart failure.SIRT1 is crucial to maintain mitochondrial structural and functional integrity to improve cardiac function in hypertrophy.Young mice (3-6months, C57BL/6J) were subjected to transverse aortic constriction (TAC) surgery, models of pressure overload-induced cardiac hypertrophy, for six weeks. Echocardiography was used to assess cardiac functions and heart tissue was collected for histological and immunoblotting analysis. Histological staining results showed that TAC for 6 weeks clearly induced hypertrophy with enlarged left ventricles compared to sham group. Echocardiographic analysis indicated that 6weeks-TAC resulted in the impairment of cardiac systolic function, in terms of ejection fraction reduction. Immunoblotting results revealed that 6weeks-TAC induced upregulation of SIRT 1 in mice heart as well as the mitochondrial biogenesis regulator PPARgamma and mitochondrial fusion regulator MFN2. Next, we will apply Sirt1flox/flox and cardiac specific Sirt1-/- (cSirt1-/-) mice in this project to determine the hypothesis that Sirt1 is crucial for these effects in protect heart from hypertrophy.

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SIRT1 and Mitochondrial Homeostasis in Heart Failure

Sirtuin 1 (SIRT 1) is a nicotinamide adenine dinucleotide (NAD+) dependent histone deacetylase. SIRT 1 has a crucial role in mediating cell survival and protecting the heart from several stress, such as hypertrophy and prevent progressive cardiac failure. Recently, SIRT1 is emerged as a crucial regulator of mitochondrial function in heart, while the mitochondrial dysfunction has been implicated in the development of heart failure.SIRT1 is crucial to maintain mitochondrial structural and functional integrity to improve cardiac function in hypertrophy.Young mice (3-6months, C57BL/6J) were subjected to transverse aortic constriction (TAC) surgery, models of pressure overload-induced cardiac hypertrophy, for six weeks. Echocardiography was used to assess cardiac functions and heart tissue was collected for histological and immunoblotting analysis. Histological staining results showed that TAC for 6 weeks clearly induced hypertrophy with enlarged left ventricles compared to sham group. Echocardiographic analysis indicated that 6weeks-TAC resulted in the impairment of cardiac systolic function, in terms of ejection fraction reduction. Immunoblotting results revealed that 6weeks-TAC induced upregulation of SIRT 1 in mice heart as well as the mitochondrial biogenesis regulator PPARgamma and mitochondrial fusion regulator MFN2. Next, we will apply Sirt1flox/flox and cardiac specific Sirt1-/- (cSirt1-/-) mice in this project to determine the hypothesis that Sirt1 is crucial for these effects in protect heart from hypertrophy.