Treatment of advanced atherosclerotic mice with the senolytic agent ABT-263 is associated with reduced indices of plaque stability and increased mortality.

ABSTRACT: The use of senolytic agents to remove senescent cells from atherosclerotic lesions is controversial. A common limitation of previous studies is the failure to rigorously define the effects of senolytic agent ABT-263 (Navitoclax) on smooth muscle cells (SMC) despite studies claiming that they are the major source of senescent cells. Moreover, there are no studies of the effect of ABT-263 on endothelial cells (EC), which along with SMC comprise 90% of α-SMA⁺ myofibroblast-like cells in the protective fibrous cap. Here we tested the hypothesis that treatment of advanced atherosclerotic mice with the ABT-263 will reduce lesion size and increase plaque stability. SMC (Myh11-CreER^T2-eYFP) and EC (Cdh5-CreER^T2-eYFP) lineage tracing Apoe^-/- mice w

SUBMITTER: Karnewar S 

PROVIDER: S-EPMC10369968 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature