OBJECTIVE: Vascular smooth muscle cells (VSMCs) that become senescent are both present within @entity731 and thought to be important to the disease process. However, senescent VSMCs are generally considered to only contribute through inaction, with failure to proliferate resulting in VSMC- and collagen-poor unstable fibrous caps. Whether senescent VSMCs can actively contribute to atherogenic processes, such as @entity32 , is unknown. APPROACH AND RESULTS: We find that senescent @entity1 VSMCs develop a proinflammatory state known as a senescence-associated secretory phenotype. Senescent @entity1 VSMCs release high levels of multiple cytokines and chemokines driven by secreted @entity1192 acting in an autocrine manner. Consequently, the VSMC senescence-associated secretory phenotype promotes chemotaxis of mononuclear cells in vitro and in vivo. In addition, senescent VSMCs release active @entity1495 , secrete less collagen, upregulate multiple inflammasome components, and prime adjacent endothelial cells and VSMCs to a proadhesive and proinflammatory state. Importantly, maintaining the senescence-associated secretory phenotype places a large metabolic burden on senescent VSMCs, such that they can be selectively killed by inhibiting @entity413 utilization. CONCLUSIONS: Senescent VSMCs may actively contribute toward the @entity32 associated with @entity731 through the @entity1192 -driven senescence-associated secretory phenotype and the priming of adjacent cells to a proatherosclerotic state. These data also suggest that inhibition of this potentially important source of @entity32 in @entity731 requires blockade of @entity1192 and not @entity1356 .

Senescent Vascular Smooth Muscle Cells Drive Inflammation Through an XXXX -Dependent Senescence-Associated Secretory Phenotype.

@entity1 :: ('9606', 'Species') :: ['human'] @entity32 :: ('MESH:D007249', 'Disease') :: ['chronic inflammation', 'inflammation'] @entity1356 :: ('3553', 'Gene') :: ['interleukin-1b'] @entity1192 :: ('3552', 'Gene') :: ['interleukin-1a'] @entity1495 :: ('4318', 'Gene') :: ['matrix metalloproteinase-9'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerosis', 'atherosclerotic plaques'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']
@entity1192 :: (3552,Gene) :: ['Interleukin-1a']
