Cytomegalovirus infection of rats increases the neointimal response to vascular injury without consistent evidence of direct infection of the vascular wall.
BACKGROUND
Previous studies suggest that infection may play a role in restenosis and atherogenesis; cytomegalovirus (CMV) is one of the implicated pathogens. To determine a potential causal role of CMV in these disease processes, we assessed whether CMV infection increases the neointimal response to injury of the rat carotid artery.


RESULTS
Carotid injury was performed on 60 rats; immediately thereafter, 30 rats were infected with rat CMV, and the other 30 were mock-infected. Six weeks later, rats were euthanized, and the salivary glands, spleen, and carotid arteries were harvested. CMV infection was associated with significant exacerbation of the neointimal response to injury (neointimal to medial ratio 0.81+/-0. 59 versus 0.31+/-0.38 in CMV-infected versus control rats; P<0.0001). This occurred despite absence of infectious virus from vascular tissues and detection of CMV DNA by polymerase chain reaction in the injured artery only at day 3 after infection. Persistent distant infection, associated with systemic cytokine response, was evidenced by isolation of infectious virus from homogenates of both salivary glands and spleen and by higher serum levels of interleukin (IL)-2 and IL-4 (but not interferon-gamma and tumor necrosis factor-alpha) in infected versus noninfected rats.


CONCLUSIONS
CMV infection of immunocompetent adult rats increases the neointimal response to vascular injury, suggesting that CMV may play a causal role in atherosclerosis/restenosis. Importantly, this CMV-induced response occurs even without the presence of virus in the vascular wall, suggesting that inflammatory and immune responses to infection of nonvascular tissues may contribute to the vascular response to injury.
Zhou
Y F
YF
Cardiovascular Research Foundation, Washington Hospital Center, Washington, DC 20010, USA. yfz1@mhg.edu
Shou
M
M
Guetta
E
E
Guzman
R
R
Unger
E F
EF
Yu
Z X
ZX
Zhang
J
J
Finkel
T
T
Epstein
S E
SE
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000209:etiology; D001161:Arteriosclerosis / Q000209:etiology*; D002340:Carotid Artery Diseases / Q000209:etiology; D016207:Cytokines / Q000097:blood; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000150:complications*; D004279:DNA, Viral / Q000032:analysis; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology* / Q000821:virology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D004279:DNA, Viral