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.
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 hypercholesterolemictransgenic 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.
Authors: Jennifer E Cole; Tina J Navin; Amanda J Cross; Michael E Goddard; Lena Alexopoulou; Anuja T Mitra; Alun H Davies; Richard A Flavell; Marc Feldmann; Claudia Monaco Journal: Proc Natl Acad Sci U S A Date: 2011-01-10 Impact factor: 11.205
Authors: Anna Lebedeva; Elena Maryukhnich; Jean-Charles Grivel; Elena Vasilieva; Leonid Margolis; Alexander Shpektor Journal: Am J Med Date: 2019-07-08 Impact factor: 4.965
Authors: Jing Zhou; Lingfeng Qin; Tai Yi; Rahmat Ali; Qingle Li; Yang Jiao; Guangxin Li; Zuzana Tobiasova; Yan Huang; Jiasheng Zhang; James J Yun; Mehran M Sadeghi; Frank J Giordano; Jordan S Pober; George Tellides Journal: Circ Res Date: 2015-09-23 Impact factor: 17.367