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Acute Loss of Apolipoprotein E Triggers an Autoimmune Response That Accelerates Atherosclerosis.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2018 Aug; Vol. 38 (8), pp. e145-e158. - Publication Year :
- 2018
-
Abstract
- Objective- Dyslipidemia is a component of the metabolic syndrome, an established risk factor for atherosclerotic cardiovascular disease, and is also observed in various autoimmune and chronic inflammatory conditions. However, there are limited opportunities to study the impact of acquired dyslipidemia on cardiovascular and immune pathology. Approach and Results- We designed a model system that allows for the conversion to a state of acute hyperlipidemia in adult life, so that the consequences of such a transition could be observed, through conditionally deleting APOE (apolipoprotein E) in the adult mouse. The transition to hypercholesterolemia was accompanied by adaptive immune responses, including the expansion of T lymphocyte helper cell 1, T follicular helper cell, and T regulatory subsets and the formation of germinal centers. Unlike steady-state Apoe <superscript>-/-</superscript> mice, abrupt loss of APOE induced rapid production of antibodies recognizing rheumatoid disease autoantigens. Genetic ablation of the germinal center reduced both autoimmunity and atherosclerosis, indicating that the immune response that follows loss of APOE is independent of atherosclerosis but nevertheless promotes plaque development. Conclusions- Our findings suggest that immune activation in response to hyperlipidemia could contribute to a wide range of inflammatory autoimmune diseases, including atherosclerosis.
- Subjects :
- Animals
Aorta metabolism
Aorta pathology
Aortic Diseases genetics
Aortic Diseases metabolism
Aortic Diseases pathology
Apolipoproteins E deficiency
Apolipoproteins E genetics
Atherosclerosis genetics
Atherosclerosis metabolism
Atherosclerosis pathology
B-Lymphocytes immunology
B-Lymphocytes metabolism
Cells, Cultured
Disease Models, Animal
Disease Progression
Dyslipidemias genetics
Dyslipidemias metabolism
Dyslipidemias pathology
Germinal Center immunology
Germinal Center metabolism
Immunity, Humoral
Inflammation genetics
Inflammation metabolism
Inflammation pathology
Mice, Inbred C57BL
Mice, Knockout, ApoE
Plaque, Atherosclerotic
Signal Transduction
T-Lymphocytes immunology
T-Lymphocytes metabolism
Time Factors
Adaptive Immunity
Aorta immunology
Aortic Diseases immunology
Apolipoproteins E immunology
Atherosclerosis immunology
Autoimmunity
Dyslipidemias immunology
Inflammation immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 38
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 29880490
- Full Text :
- https://doi.org/10.1161/ATVBAHA.118.310802