Dendritic cells pulsed with malondialdehyde modified low density lipoprotein aggravate atherosclerosis in Apoe−/− mice

• Published in: Atherosclerosis Vol. 209; no. 2; pp. 436 - 441
• Main Authors: Hjerpe, Charlotta, Johansson, Daniel, Hermansson, Andreas, Hansson, Göran K, Zhou, Xinghua
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.04.2010; Elsevier
• Subjects: Animals; Apolipoproteins E - deficiency; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - immunology; Atherosclerosis - pathology; Biological and medical sciences; Blood and lymphatic vessels; Blood. Blood coagulation. Reticuloendothelial system; Cardiology. Vascular system; Cardiovascular; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - pathology; Female; Immune system; Lipoproteins, LDL - pharmacology; Low density lipoprotein; Malondialdehyde - analogs & derivatives; Malondialdehyde - pharmacology; Medical sciences; Medicin och hälsovetenskap; Mice; Pharmacology. Drug treatments; T-Lymphocytes, Regulatory - immunology; Mice; Dendritic cells; Low density lipoprotein; Atherosclerosis; Immune system; Dendritic cell; Rodentia; Cardiovascular disease; Lipoprotein; Vascular disease; Vertebrata; Mammalia; Mouse; Animal
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2009.10.003

Abstract Objective Atherosclerosis is an inflammatory disease involving activation of adaptive and innate immune responses to modified lipoproteins. Dendritic cells (DCs), which are professional antigen-presenting cells that activate T cells, are present in atherosclerotic lesions but their role for atherosclerosis-related immunity is unclear. Methods and results To evaluate the role of DC in atherosclerosis, DCs pulsed with malondialdehyde modified low density lipoprotein (MDA-LDL) were transferred into Apoe−/− mice. The extent of disease was measured in the aortic root and was compared to that in animals treated with Keyhole Limpet Hemocyanin (KLH) pulsed DCs and to untreated animals. Mice receiving MDA-LDL pulsed DCs showed significantly larger atherosclerotic lesions compared to controls, with increased inflammation in the lesions and antigen-specific immune responses. Furthermore, MDA-LDL administration in complete Freund's adjuvant, which is atheroprotective, led to the induction of regulatory T cells whereas MDA-LDL-DCs treatment did not, suggesting that modulation of immune properties can result in different effects on atherosclerosis. Conclusions DCs presenting components of LDL promote specific immunity to their antigen, increase lesion inflammation and accelerate atherosclerosis.