Effect of Low-Dose Aspirin on Vascular Inflammation, Plaque Stability, and Atherogenesis in Low-Density Lipoprotein Receptor–Deficient Mice

TLDR

Atherosclerosis is a complex vascular inflammatory disease for which low‑dose aspirin is a mainstay of prevention of vascular complications. The study aimed to determine how low‑dose aspirin affects vascular inflammation, plaque composition, and atherogenesis in LDL receptor–deficient mice on a high‑fat diet. The authors used LDL receptor–deficient mice fed a high‑fat diet to assess aspirin’s impact on vascular inflammation, plaque composition, and atherogenesis. Low‑dose aspirin markedly reduced circulating and vascular inflammatory mediators, suppressed NF‑κB activity, and diminished atherosclerotic lesion extent while increasing smooth muscle cells and collagen, thereby enhancing plaque stability and exerting an anti‑atherogenic effect in LDL receptor–deficient mice.

Abstract

Background— Atherosclerosis is a complex vascular inflammatory disease. Low-dose aspirin is a mainstay in the prevention of vascular complications of atherosclerosis. We wished to determine the effect of low-dose aspirin on vascular inflammation, plaque composition, and atherogenesis in LDL receptor–deficient mice fed a high fat diet. Methods and Results— In LDL receptor–deficient mice fed a high fat diet compared with control mice, low-dose aspirin induced a significant decrease in circulating levels and vascular formation of soluble intercellular molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin-12p 40, without affecting lipid levels. This was associated with significant reduction of the nuclear factor κB activity in the aorta. Low-dose aspirin also significantly reduced the extent of atherosclerosis. Finally, aortic vascular lesions of the aspirin-treated animals showed 57% reduction ( P <0.05) in the amount of macrophage cells, 77% increase in smooth muscle cells ( P <0.05), and 23% increase in collagen ( P <0.05). Conclusions— Our results suggest that in murine atherosclerosis, low-dose aspirin suppresses vascular inflammation and increases the stability of atherosclerotic plaques, both of which, together with its antiplatelet activity, contribute to its antiatherogenic effect. We conclude that low-dose aspirin might be rationally evaluated in the progression and evolution of human atherosclerotic plaque.