Senolytics prevent caveolar Ca_V 3.2-RyR axis malfunction in old vascular smooth muscle.

ABSTRACT: Aging is a major risk factor for cardiovascular diseases. Our previous studies demonstrate that aging impairs the caveolar T-type Ca_V 3.2-RyR axis for extracellular Ca²⁺ influx to trigger Ca²⁺ sparks in vascular smooth muscle cells (VSMCs). We hypothesize that the administration of senolytics, which can selectively clear senescent cells, could preserve the caveolar Ca_V 3.2-RyR axis in aging VSMCs. In this study, 10-month-old mice were administered the senolytics cocktail consisting of dasatinib (5 mg/kg) and quercetin (50 mg/kg) or vehicle bi-weekly for 4 months. Using VSMCs from mouse mesenteric arteries, we found that Ca²⁺ sparks were diminished after caveolae disruption by methyl-β-cyclodextrin (10 mM) in cells from D + Q treated bu

SUBMITTER: Lin J 

PROVIDER: S-EPMC10652315 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature