PMID- 19897195 OWN - NLM STAT- MEDLINE DCOM- 20100614 LR - 20131121 IS - 1879-1484 (Electronic) IS - 0021-9150 (Linking) VI - 209 IP - 2 DP - 2010 Apr TI - Dendritic cells pulsed with malondialdehyde modified low density lipoprotein aggravate atherosclerosis in Apoe(-/-) mice. PG - 436-41 LID - 10.1016/j.atherosclerosis.2009.10.003 [doi] AB - 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. CI - Copyright 2009 Elsevier Ireland Ltd. All rights reserved. FAU - Hjerpe, Charlotta AU - Hjerpe C AD - Centre for Molecular Medicine and Department of Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Johansson, Daniel AU - Johansson D FAU - Hermansson, Andreas AU - Hermansson A FAU - Hansson, Goran K AU - Hansson GK FAU - Zhou, Xinghua AU - Zhou X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091107 PL - Ireland TA - Atherosclerosis JT - Atherosclerosis JID - 0242543 RN - 0 (Apolipoproteins E) RN - 0 (Lipoproteins, LDL) RN - 0 (malondialdehyde-low density lipoprotein, mouse) RN - 4Y8F71G49Q (Malondialdehyde) SB - IM MH - Animals MH - Apolipoproteins E/*deficiency MH - Atherosclerosis/immunology/*pathology MH - Dendritic Cells/immunology/*pathology MH - Female MH - Lipoproteins, LDL/*pharmacology MH - Malondialdehyde/*analogs & derivatives/pharmacology MH - Mice MH - T-Lymphocytes, Regulatory/immunology EDAT- 2009/11/10 06:00 MHDA- 2010/06/15 06:00 CRDT- 2009/11/10 06:00 PHST- 2009/05/20 00:00 [received] PHST- 2009/09/28 00:00 [revised] PHST- 2009/10/02 00:00 [accepted] PHST- 2009/11/10 06:00 [entrez] PHST- 2009/11/10 06:00 [pubmed] PHST- 2010/06/15 06:00 [medline] AID - S0021-9150(09)00830-2 [pii] AID - 10.1016/j.atherosclerosis.2009.10.003 [doi] PST - ppublish SO - Atherosclerosis. 2010 Apr;209(2):436-41. doi: 10.1016/j.atherosclerosis.2009.10.003. Epub 2009 Nov 7.