Basic/Translational Science -> Whole Animal Electrophysiology and Pharmacology (includes Neurohumoral Modulation)
D-PO05 - Poster Session V (ID 39)
Poster
D-PO05-060 - Navitoclax Improved Cardiac Function And Electrophysiological Characteristics In Mice With Heart Failure (ID 529)
Abstract
Background: Heart failure is a major health problem with huge economic burden worldwide.
Objective: The aim of this study was to evaluate the therapeutic potential of navitoclax in treatment of angiotensin II (Ang II)-induced HF in mice.
Methods: Navitoclax or vehicle was administrated in mice with Ang II-induced HF. Cardiac function and electrophysiology were assessed before and after the administration of navitoclax. Cardiac remodeling including morphological changes, fibrosis and inflammatory responses were analyzed in both myocardial tissue and isolated primary cardiomyocytes and cardiac fibroblasts.
Results: Echocardiography of mice showed that navitoclax reversed cardiac dysfunction by improving left ventricular ejection fraction, as compared with vehicle (vehicle:45.88±2.19%; navitoclax: 54.70±1.65%, p<0.01). In cardiac electrophysiological testing, navitoclax increased conduction velocity (vehicle: 1.37±0.05mm/ms; navitoclax: 1.69±0.08mm/ms, p<0.05) and decreased susceptibility to ventricular tachy-arrhythmia induced by programmed electrical stimulation. Histopathological staining, immunofluorescence and western blotting examination demonstrated that navitoclax ameliorated Ang II-induced cardiac fibrosis, hypertrophy and inflammatory response. Moreover, navitoclax augmented apoptosis of Ang II-induced senescent fibroblasts.
Conclusion: Navitoclax improved cardiac function and electrophysiological characteristics via decreasing cardiac fibrosis, hypertrophy and inflammatory in mice with HF. Pharmacological clearance of senescent cells may be a potential therapeutic approach in heart failure with reduced ejection fraction.
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Objective: The aim of this study was to evaluate the therapeutic potential of navitoclax in treatment of angiotensin II (Ang II)-induced HF in mice.
Methods: Navitoclax or vehicle was administrated in mice with Ang II-induced HF. Cardiac function and electrophysiology were assessed before and after the administration of navitoclax. Cardiac remodeling including morphological changes, fibrosis and inflammatory responses were analyzed in both myocardial tissue and isolated primary cardiomyocytes and cardiac fibroblasts.
Results: Echocardiography of mice showed that navitoclax reversed cardiac dysfunction by improving left ventricular ejection fraction, as compared with vehicle (vehicle:45.88±2.19%; navitoclax: 54.70±1.65%, p<0.01). In cardiac electrophysiological testing, navitoclax increased conduction velocity (vehicle: 1.37±0.05mm/ms; navitoclax: 1.69±0.08mm/ms, p<0.05) and decreased susceptibility to ventricular tachy-arrhythmia induced by programmed electrical stimulation. Histopathological staining, immunofluorescence and western blotting examination demonstrated that navitoclax ameliorated Ang II-induced cardiac fibrosis, hypertrophy and inflammatory response. Moreover, navitoclax augmented apoptosis of Ang II-induced senescent fibroblasts.
Conclusion: Navitoclax improved cardiac function and electrophysiological characteristics via decreasing cardiac fibrosis, hypertrophy and inflammatory in mice with HF. Pharmacological clearance of senescent cells may be a potential therapeutic approach in heart failure with reduced ejection fraction.
