Abstract 17307: Mice with Genetic Ablation of Ceacam1 Develop Spontaneous Atherosclerosis
Atherosclerosis is a multifaceted disease resulting from inflammation, dyslipidemia, and endothelial dysfunction. Defining a mechanistic link between these risk factors has been limited by the lack of an experimental model that completely mimics the human disease. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates insulin and lipid metabolism in liver; down regulates inflammatory response in activated T-lymphocytes, and preserves endothelial cell integrity. Null mutation of Ceacam1 (Cc1−/−) causes insulin resistance resulting from impaired insulin clearance, visceral obesity, dyslipidemia, hepatic steatosis and high plasma triglyceride and fatty acid levels. We herein, tested whether loss of CEACAM1 also leads to atherosclerosis. Histological analysis of the vasculature revealed that at six months of age, Cc1−/− mice exhibit atherosclerotic lesions. By comparison to their wild-type Cc1+/+ counterparts, Cc1−/− null mice exhibit moderately higher total, VLDL- and LDL-plasma cholesterol levels. Quantitative Real-time PCR analysis of the ascending aorta revealed elevation in the mRNA levels of F4/80 macrophage marker, TNFα, vascular adhesion molecule 1 (VCAM1), and CD3+, CD4+, CD8+T cells. Histological analysis of the vasculature revealed a significant decrease in endothelial glycocalyx. mRNA levels of pro-angiogenic factors in the aorta were reduced, suggesting decreased endothelial integrity and endothelial dysfunction. Because loss of CEACAM1 function in inflammation, endothelial integrity, and insulin clearance could independently promote the initiation and progression of atherosclerosis, our data do not identify the exact mechanism of the disease in this mouse. However, they promote the Cc1−/− mouse as a novel model to investigate the mechanistic link between metabolic derangement, endothelial dysfunction, and atherosclerosis, as well as identify CEACAM1 as a potential molecular target.
- © 2010 by American Heart Association, Inc.