Abstract 154: Vaccination Using Advanced Glycation End Product of Low-Density Lipoprotein Pulsed Dendritic Cells Reduces Atherosclerosis in Diabetic Apoe-/- Mice
Rationale and Objective Accumulation of advanced glycation end-product of low density lipoprotein (AGE-LDL) attributable to hyperglycemia in diabetes contributes to the progression of atherosclerosis (AS). Previous studies showed that immunization against modified LDL reduce AS in animal models. Due to their potent capacity to stimulate T cells, dendritic cells (DCs) are being investigated in immunotherapy approaches. In this study, we immunized AGE-LDL pulsed DCs to diabetic apoE-/- mice and examined the effects on AS.
Methods and results The present study explored AS in streptozotocin-induced diabetic apoE-/- mice that were randomized (n=36) to receive no treatment, AGE-LDL pulsed DCs immunization, or ovalbumin (AS-irrelevant antigen) pulsed DCs immunization. Bone marrow-derived DCs were cultured for 10 days in the presence of granulocyte-macrophage colony-stimulating factor. Immature DCs were matured by lipopolysaccharide and pulsed with AGE-LDL or ovalbumin. These DCs were transferred five times to diabetic apoE-/- mice before the induction of AS by western-type diet feeding. Vaccination using AGE-LDL pulsed DCs resulted in a marked reduction in aortic root and carotid artery lesion size, and an increase in plaque stability which was independent of hypercholesterolemia in mice. Transfer of ovalbumin pulsed DCs did not influence lesion size or stability. Vaccination using AGE-LDL pulsed DCs resulted in AGE-LDL-specific Th1 cell activation, and induction of AGE-LDL-specific IgG. Furthermore, AGE-LDL pulsed DCs transfer resulted in impressed function of macrophages with a marked inhibition of TLR4-mediated signaling pathway.
Conclusion These findings demonstrate for the first time that vaccination with AGE-LDL-pulsed DCs provides a novel strategy for the immunomodulation of atherosclerosis in diabetes.
- © 2012 by American Heart Association, Inc.