(Circulation. 1999;100:1569-1575.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Cytomegalovirus Infection of Rats Increases the Neointimal Response to Vascular Injury Without Consistent Evidence of Direct Infection of the Vascular Wall
From the Cardiovascular Research Foundation, Washington Hospital Center, Washington, DC, and the Cardiology Branch, NHLBI, and Clinical Pathology Department, Clinical Center, National Institutes of Health, Bethesda, Md.
Correspondence to Yi Fu Zhou, MD, Cardiovascular Research Foundation, Suite 4B-1, 110 Irving St, Washington Hospital Center, Washington, DC 20010. E-mail yfz1{at}mhg.edu
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.
Methods and 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-
and tumor necrosis factor-
) 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.
Key Words: viruses • balloon • restenosis • atherosclerosis • cytokines
This article has been cited by other articles:
 |
|
 |
|
  S. E. Epstein, J. Zhu, A. H. Najafi, and M. S. Burnett Insights Into the Role of Infection in Atherogenesis and in Plaque Rupture Circulation, June 23, 2009; 119(24): 3133 - 3141. [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Gombos, V. Wolan, K. McDonald, and D. G. Hemmings Impaired vascular function in mice with an active cytomegalovirus infection Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H937 - H945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Bolovan-Fritts and S. A. Spector Endothelial damage from cytomegalovirus-specific host immune response can be prevented by targeted disruption of fractalkine-CX3CR1 interaction Blood, January 1, 2008; 111(1): 175 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. H. Betjes, N. H. R. Litjens, and R. Zietse Seropositivity for cytomegalovirus in patients with end-stage renal disease is strongly associated with atherosclerotic disease Nephrol. Dial. Transplant., November 1, 2007; 22(11): 3298 - 3303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Bolovan-Fritts, R. N. Trout, and S. A. Spector High T-cell response to human cytomegalovirus induces chemokine-mediated endothelial cell damage Blood, September 15, 2007; 110(6): 1857 - 1863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F.C. Gibson III, H. Yumoto, Y. Takahashi, H.-H. Chou, and C.A. Genco Innate Immune Signaling and Porphyromonas gingivalis-accelerated Atherosclerosis Journal of Dental Research, February 1, 2006; 85(2): 106 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Lindsberg and A. J. Grau Inflammation and Infections as Risk Factors for Ischemic Stroke Stroke, October 1, 2003; 34(10): 2518 - 2532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Muhlestein and J. L. Anderson Infectious Serology and Atherosclerosis: How Burdensome Is the Risk? Circulation, January 21, 2003; 107(2): 220 - 222. [Full Text] [PDF]
|
|
|
|
|
|
H. D. Danenberg, F. G. P. Welt, M. Walker III, P. Seifert, G. S. Toegel, and E. R. Edelman Systemic Inflammation Induced by Lipopolysaccharide Increases Neointimal Formation After Balloon and Stent Injury in Rabbits Circulation, June 18, 2002; 105(24): 2917 - 2922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Epstein The Multiple Mechanisms by Which Infection May Contribute to Atherosclerosis Development and Course Circ. Res., January 11, 2002; 90(1): 2 - 4. [Full Text] [PDF]
|
|
|
|
|
|
D. Virok, Z. Kis, L. Karai, L. Intzedy, K. Burian, A. Szabo, B. Ivanyi, E. Gonczol, and M. S. Elkind Chlamydia pneumoniae in Atherosclerotic Middle Cerebral Artery Editorial Comment Stroke, September 1, 2001; 32(9): 1973 - 1976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. TIKKANEN, E. A. KALLIO, C. A. BRUGGEMAN, P. K. KOSKINEN, and K. B. LEMSTROM Prevention of Cytomegalovirus Infection-enhanced Experimental Obliterative Bronchiolitis by Antiviral Prophylaxis or Immunosuppression in Rat Tracheal Allografts Am. J. Respir. Crit. Care Med., August 15, 2001; 164(4): 672 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Guetta, E. M Scarpati, and P. E DiCorleto Effect of cytomegalovirus immediate early gene products on endothelial cell gene activity Cardiovasc Res, June 1, 2001; 50(3): 538 - 546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Epstein, J. Zhu, M. S. Burnett, Y. F. Zhou, G. Vercellotti, and D. Hajjar Infection and Atherosclerosis : Potential Roles of Pathogen Burden and Molecular Mimicry Arterioscler Thromb Vasc Biol, June 1, 2000; 20(6): 1417 - 1420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. F. Zhou, M. Shou, R. F Harrell, Z. X. Yu, E. F Unger, and S. E Epstein Chronic non-vascular cytomegalovirus infection: effects on the neointimal response to experimental vascular injury Cardiovasc Res, March 1, 2000; 45(4): 1019 - 1025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. M. Miller Gender, Estrogen, and NOS : Cautions About Generalizations Circ. Res., November 26, 1999; 85(11): 979 - 981. [Full Text] [PDF]
|
|