Senolytic Agent Navitoclax Inhibits Angiotensin II-Induced Heart Failure in Mice.

Journal of Cardiovascular Pharmacology
Kangni JiaQi Jin

Abstract

Navitoclax, which is a type of senolytic drug, selectively eliminates senescent cells. This study aimed to evaluate the therapeutic potential of navitoclax in treatment of angiotensin II (Ang II)-induced heart failure in mice. Navitoclax or vehicle was administrated in mice with Ang II-induced heart failure. Cardiac function and electrophysiology were assessed before and after administration of navitoclax. Cardiac remodeling, including morphological changes, fibrosis, and inflammatory responses, was analyzed in myocardial tissue. Cellular effects of navitoclax were validated in isolated primary cardiomyocytes and cardiac fibroblasts in vitro. Echocardiography of mice showed that navitoclax improved cardiac dysfunction by improving the left ventricular ejection fraction (vehicle: 45.88 ± 2.19%; navitoclax: 54.70 ± 1.65%, P < 0.01). In cardiac electrophysiological testing, navitoclax increased conduction velocity (vehicle: 1.37 ± 0.05 mm/ms; navitoclax: 1.69 ± 0.08 mm/ms, P < 0.05) and decreased susceptibility to ventricular tachyarrhythmia induced by programmed electrical stimulation. Histopathological staining, immunofluorescence, and western blotting examinations showed that navitoclax ameliorated Ang II-induced cardiac fibros...Continue Reading

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Citations

Feb 14, 2021·Cancers·Valerie J CarpenterDavid A Gewirtz
Apr 2, 2021·International Journal of Cardiology·Ampadu O JacksonShiyin Long
May 28, 2021·Circulation Research·Joel G RurikJonathan A Epstein
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May 9, 2021·Cardiovascular Research·Maggie S ChenJessica C Garbern
Nov 10, 2021·Clinical Science·Jeffrey KingsleySatoru Eguchi

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