Abstract 11284: Angiopoietin-Like Protein2 (Angptl2) Induces the Development of Aortic Aneurysms Through Increasing the Chronic Inflammation in Aortic Walls
Abdominal aortic aneurysm (AAA) is characterized by aneurysmal morphological changes with low-grade chronic inflammation of atherosclerotic aortic walls. However, molecular mechanism underlying this persistent inflammation in the development of AAA has not been elucidated well. We previously reported that adipocyte-derived Angptl2 is a key mediator linking obesity to adipose tissue inflammation and systemic insulin resistance (Cell Metabolism 2009). Recently, we found that the expression levels of Angptl2 mRNA in aneurysmal lesion of AAA patients were significantly increased compared to the surrounding non-aneurysmal lesion (N=7, p<0.001). In this study, we examined whether Angptl2 contributes to the pathogenesis of AAA formation. Firstly, we found that Angptl2 protein was abundantly expressed in residential vascular smooth muscle cells (VSMCs) and infiltrated macrophages in aneurysmal lesion of AAA patients. We next examined whether Angptl2 expression was induced in the process of CaCl2-induced AAA model in mice. RT-PCR analysis revealed that Angptl2 expression was markedly increased at day 7 after operation and sustained until day 42, while the expression levels of Tnf-α, Il-6, and Il-1β were peaked at day 3 and decreased rapidly until day 7. Therefore, we examined whether deficiency of Angptl2 affects the CaCl2-induced AAA formation in Angptl2-knockout (KO) mice. Interestingly, the sizes of AAA at day 28 in Angptl2 KO mice were significantly decreased compared to wildtype mice (n=8, p<0.005). To identify the culprit cells secreting Angptl2 in AAA lesion, we transplanted bone marrow (BM) cells from Angptl2 KO mice or littermate wildtype controls into lethally irradiated wildtype recipients, and transplanted BM cells from littermate wildtype controls into lethally irradiated Angptl2 KO recipients. Subsequently, we generated CaCl2-induced AAA model in these recipient mice. The sizes of CaCl2-induced AAA at day 28 in the recipients of Angptl2-deficient BM cells were significantly attenuated compared to those in either type of recipients of wildtype control BM cells (n=8, p<0.001). These results suggest that infiltrated macrophages-derived Angptl2 induced vascular chronic inflammation, resulting in progression of AAA pathogenesis.
- © 2010 by American Heart Association, Inc.