Influenza infection exerts prominent inflammatory and thrombotic effects on the atherosclerotic plaques of apolipoprotein E-deficient mice.
BACKGROUND
The role of infection in the development and complications of atherosclerosis has been the focus of much attention. We reported previously that influenza vaccination was associated with reduced risk of recurrent myocardial infarction. Here, we report the effect of influenza A virus on the apolipoprotein E-deficient (apoE(-/-)) mouse, an animal model of atherosclerosis.


RESULTS
Twenty-four apoE(-/-) mice >24 months old were injected with 1 LD(50) (lethal dose 50) of influenza A virus. Ten wild-type C57BL/6 infected mice and 11 noninfected age-matched apoE(-/-) mice served as controls. Multiple aortic sections were studied histologically 3, 5, and 10 days later. The infected mice showed markedly increased intimal cellularity compared with the noninfected apoE(-/-) mice. No aortic abnormalities were seen in infected wild-type mice. Ten infected apoE(-/-) mice had a significant subendothelial infiltrate composed of a heterogeneous group of cells that stained positively for smooth muscle cell actin, F4/80 (macrophages), and CD3 (T lymphocytes). One case of subocclusive platelet and fibrin-rich thrombus was seen.


CONCLUSIONS
This study shows that influenza infection promotes inflammation, smooth muscle cell proliferation, and fibrin deposition in atherosclerotic plaques.
Naghavi
Morteza
M
Center for Vulnerable Plaque Research at the University of Texas-Houston Health Science Center, Division of Cardiology, and the Texas Heart Institute, Houston, TX 77030, USA. mnaghavi@vp.org
Wyde
Philip
P
Litovsky
Silvio
S
Madjid
Mohammad
M
Akhtar
Adeeba
A
Naguib
Sameh
S
Siadaty
Mir Said
MS
Sanati
Susan
S
Casscells
Ward
W
D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000150:complications / Q000235:genetics / Q000473:pathology*; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000209:etiology / Q000473:pathology*; D009980:Influenza A virus / Q000472:pathogenicity; D007928:Lethal Dose 50; D008168:Lung / Q000473:pathology / Q000821:virology; D008214:Lymphocytes / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009976:Orthomyxoviridae Infections / Q000150:complications*; D010974:Platelet Aggregation; D015996:Survival Rate; D013927:Thrombosis / Q000209:etiology / Q000473:pathology*
D001057:Apolipoproteins E