BACKGROUND: -Although vascular smooth muscle cell (VSMC) proliferation is implicated in atherogenesis, VSMCs in advanced plaques and cultured from plaques show evidence of VSMC senescence and DNA damage. In particular plaque VSMCs show shortening of telomeres, which can directly induce senescence. Senescence can have multiple effects on plaque development and morphology; however, the consequences of VSMC senescence or the mechanisms underlying VSMC senescence in @entity731 are mostly unknown. METHODS AND RESULTS: -We examined expression of proteins that protect telomeres in VSMCs derived from @entity1 plaques and normal vessels. Plaque VSMCs showed reduced expression and telomere binding of @entity18049 ( @entity18049 ), associated with increased DNA damage. @entity18049 expression was regulated by @entity899 -dependent degradation of @entity18049 protein. To examine the functional consequences of loss of @entity18049 , we expressed @entity18049 or a @entity18049 functional mutant ( @entity68534 ) as either gain or loss of function studies in vitro and in @entity6970 (-/-) @entity19 . @entity18049 overexpression bypassed senescence, reduced DNA damage, and accelerated DNA repair, whereas @entity18049 (188A) showed opposite effects. @entity19 expressing VSMC-specific @entity18049 ( @entity68534 ) showed increased @entity731 and @entity39 core formation in vivo, whereas VSMC-specific @entity18049 increased relative fibrous cap and decreased @entity39 core areas. @entity18049 protected against @entity731 independent of secretion of senescence-associated cytokines. CONCLUSIONS: -We conclude that plaque VSMC senescence in @entity731 is associated with loss of @entity18049 . VSMC senescence promotes both @entity731 and features of plaque vulnerability, identifying prevention of senescence as a potential target for intervention.

Vascular Smooth Muscle Cell Senescence Promotes XXXX and Features of Plaque Vulnerability.

@entity1 :: ('9606', 'Species') :: ['human'] @entity6970 :: ('11816(Tax:10090)', 'Gene') :: ['ApoE'] @entity68534 :: ('c|SUB|T|188|A', 'DNAMutation') :: ['T188A'] @entity39 :: ('MESH:D009336', 'Disease') :: ['necrotic'] @entity18049 :: ('21750(Tax:10090)', 'Gene') :: ['Telomeric repeat-binding factor-2', 'TRF2'] @entity899 :: ('22060(Tax:10090)', 'Gene') :: ['p53'] @entity19 :: ('10090', 'Species') :: ['mice', 'Transgenic mice'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerosis']
@entity731 :: (MESH:D050197,Disease) :: ['Atherosclerosis']
