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.
Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia 19104, USA.
Tillmann
T
Cyrus
Syuan
S
Sung
Lei
L
Zhao
Colin D
CD
Funk
Syun
S
Tang
Domenico
D
Praticò
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