Chronic immune reactivity against persisting microbial antigen in the vasculature exacerbates atherosclerotic lesion formation
- PMID: 17656668
- DOI: 10.1161/ATVBAHA.107.141846
Chronic immune reactivity against persisting microbial antigen in the vasculature exacerbates atherosclerotic lesion formation
Abstract
Objective: The purpose of this study was to examine the relative contribution of different immunopathological mechanisms during murine cytomegalovirus (MCMV)-mediated acceleration of atheroma formation in apolipoprotein E-deficient (apoE-/-) mice.
Methods and results: To distinguish between the effects of systemic activation and cognate immune reactivity against a pathogen-derived persisting antigen in the vasculature, we used hypercholesterolemic transgenic mice constitutively expressing the beta-galactosidase (beta-gal) transgene in the cardiovascular system (apoE-/- x SM-LacZ). After infection with beta-gal-recombinant MCMV-LacZ, apoE-/-, and apoE-/- x SM-LacZ mice mounted comparable cellular immune responses against the virus. Beta-gal-specific CD(+ T cells expanded rapidly and remained detectable for at least 100 days in both mouse strains. However, compared with apoE-/- mice, apoE-/- x SM-LacZ mice developed drastically accelerated atherosclerosis. Moreover, atherosclerotic lesions in MCMV-LacZ-infected apoE-/- x SM-LacZ but not apoE-/- mice were associated with pronounced inflammatory infiltrates.
Conclusions: Taken together, our data indicate that chronic immune reactivity against pathogen-derived antigens persisting in the vasculature significantly exacerbates atherogenesis.
Similar articles
-
Linking immune-mediated arterial inflammation and cholesterol-induced atherosclerosis in a transgenic mouse model.Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12752-7. doi: 10.1073/pnas.220427097. Proc Natl Acad Sci U S A. 2000. PMID: 11050173 Free PMC article.
-
Role of C-reactive protein in atherogenesis: can the apolipoprotein E knockout mouse provide the answer?Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):1641-6. doi: 10.1161/01.ATV.0000171983.95612.90. Epub 2005 May 26. Arterioscler Thromb Vasc Biol. 2005. PMID: 15920030
-
Atherosclerosis development in apolipoprotein E-null mice deficient for CD69.Cardiovasc Res. 2009 Jan 1;81(1):197-205. doi: 10.1093/cvr/cvn227. Epub 2008 Aug 14. Cardiovasc Res. 2009. PMID: 18703531
-
Dendritic cells in cytomegalovirus infection: viral evasion and host countermeasures.APMIS. 2009 May;117(5-6):413-26. doi: 10.1111/j.1600-0463.2009.02449.x. APMIS. 2009. PMID: 19400865 Review.
-
Evasion of cytotoxic T lymphocytes by murine cytomegalovirus.Semin Immunol. 2001 Feb;13(1):19-26. doi: 10.1006/smim.2001.0292. Semin Immunol. 2001. PMID: 11289796 Review.
Cited by
-
The immunologic injury composite with balloon injury leads to dyslipidemia: a robust rabbit model of human atherosclerosis and vulnerable plaque.J Biomed Biotechnol. 2012;2012:249129. doi: 10.1155/2012/249129. Epub 2012 Sep 4. J Biomed Biotechnol. 2012. PMID: 22988422 Free PMC article. Clinical Trial.
-
Unexpected protective role for Toll-like receptor 3 in the arterial wall.Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2372-7. doi: 10.1073/pnas.1018515108. Epub 2011 Jan 10. Proc Natl Acad Sci U S A. 2011. PMID: 21220319 Free PMC article.
-
Human cytomegalovirus increases HUVEC sensitivity to thrombin and modulates expression of thrombin receptors.J Thromb Thrombolysis. 2010 Aug;30(2):164-71. doi: 10.1007/s11239-010-0447-7. J Thromb Thrombolysis. 2010. PMID: 20155436
-
T cells in arteritis and atherosclerosis.Curr Opin Lipidol. 2008 Oct;19(5):469-77. doi: 10.1097/mol.0b013e32830bfdc2. Curr Opin Lipidol. 2008. PMID: 18841594 Free PMC article. Review.
-
Immune modulation during latent herpesvirus infection.Immunol Rev. 2012 Jan;245(1):189-208. doi: 10.1111/j.1600-065X.2011.01074.x. Immunol Rev. 2012. PMID: 22168421 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases
Miscellaneous
