Cardiology Research and Practice · Nov 10, 2026

Senescence‐Associated Secretory Phenotype (SASP) and Atherosclerotic Plaque Inflammation: Natural Product‐Based Interventions and Implications for Personalized Therapy

By Liu D, Kornthong N, Yu S et al.

Atherosclerosis underlies most ischemic cardiovascular events, and its prevalence rises with population aging. Cellular senescence is increasingly implicated as a driver of plaque progression, although the causal evidence is largely preclinical. Senescent endothelial cells, smooth muscle cells, and macrophages acquire a senescence‐associated secretory phenotype (SASP), releasing cytokines, chemokines, proteases, and procoagulant factors. These factors sustain plaque inflammation, weaken the fibrous cap, and increase rupture risk. In this narrative review, we link SASP signaling to plaque instability through NF‐κB, p38 MAPK, mTOR, NLRP3, and cGAS–STING signaling. We then evaluate tetramethylpyrazine (ligustrazine), quercetin, fisetin, resveratrol, and curcumin against an operational definition reserving senolytic and senomorphic for effects shown in confirmed senescent cells. On that standard, only quercetin and fisetin qualify; for the other three, the vascular evidence is anti‐inflammatory, antioxidant, or senescence‐preventive rather than directed at established senescent cells. Tetramethylpyrazine protects the endothelial glycocalyx and reduces plaque area in atherosclerotic rabbits. Dasatinib plus quercetin benefits ApoE−/− mice, whereas the only human evidence comes from quercetin monotherapy, which improved endothelium‐dependent vasodilation in vessels from symptomatic male, but not female, bypass patients ex vivo. Because senescence burden varies between individuals, we consider how multiomics profiling might stratify patients. The evidence remains mechanistic and hypothesis‐generating, with limited human cardiovascular interventional data: Much of it was recorded in cells never shown to be senescent, and no formulation has been shown to reach the human vessel wall. Targeting the SASP therefore requires trial evidence rather than an established basis for precision medicine.

doi.org/10.1155/crp/6765242Open accessPubMed 43017262Interventions