Analysis of vascular cell senescence to identify interventions in atherosclerosis

National Institute On Aging

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Abstract

The development of age-related multi-factorial diseases such as atherosclerosis is associated with persistent systemic inflammation. However, the interplay between aging, inflammation, and VSMC senescence is not well understood. Senescent cells exhibit a senescence-associated secretory phenotype (SASP) that includes the production of many proinflammatory cytokines (e.g., IL-6, IL-8, and IL-1), as well as chemokines (e.g., CCL2), adhesion molecules (e.g., ICAM-1), and angiogenic factors (e.g., VEGF). Recently, we found that Dipeptidyl peptidase 4 (DPP4) is highly expressed on the surface of senescent cells. While the effect of DPP4 on VSMCs is not well understood, DPP4 inhibitors such as Vildagliptin are clinically used to treat Diabetes. In animal models, gliptins have shown the ability to reduce atherosclerosis and inflammation, independent of DPP4s canonical role in glucose metabolism. Thus, we proposed to investigate the ability of DPP4 inhibitors to reduce the burden of senescent VSMCs in vascular disease progression.