Effect of low-dose aspirin on vascular inflammation, plaque stability, and atherogenesis in low-density lipoprotein receptor-deficient mice.
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.


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-alpha, interleukin-12p 40, without affecting lipid levels. This was associated with significant reduction of the nuclear factor kappaB 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.
Cyrus
Tillmann
T
Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia 19104, USA.
Sung
Syuan
S
Zhao
Lei
L
Funk
Colin D
CD
Tang
Syun
S
Praticò
Domenico
D
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D046508:Culture Techniques; D016207:Cytokines / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics*; D014657:Vasculitis / Q000188:drug therapy* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D016328:NF-kappa B; D011973:Receptors, LDL; D001241:Aspirin