High fat diet containing cholesterol induce aortic aneurysm through recruitment and proliferation of circulating agranulocytes in apoE knock out mice model

Abstract

We studied and compared the efficiency of induction aneurysm in apo E mice by using high fat diet and Ang II. Aneurysm induced in 6 week old male apo E −/− mice by subcutaneous release of Ang II injection for 45 days. Also, aneurysm was induced in three month old male apo E by administration of high fat diet for a period of three months. No difference in body weight in Ang II treated mice. But, increase in body weight and mean arterial blood pressure observed in high fat diet group animals. Highly significant increase in total cholesterol, TG, LDL and significant decrease in HDL level were observed in Ang II treated animals. Significant increase in total cholesterol, but no changes in TG, LDL, HDL levels were observed in high fat diet group. Higher percentage of circulating monocytes was observed in ang II treated group but more number of circulating lymphocytes were observed in high fat diet group in FACS analysis. In histopathology, intimal layer of abdominal aorta was completely replaced by chronic inflammatory cells particularly macrophages (80%) which appeared as foam cells and lymphocytes (20%) in ang II treated animals. Degradation of elastin, infiltration of lymphocytes, chondrocytes and cellular migration towards media were observed in the abdominal aorta of high fat diet group. Real time analysis and immunofluorescence assay supports over expression of Vcam 1 Icam1, MCP 1and MMP2 genes were observed in Ang II treated animals. In immunofluorescence assay, over expression of Mac 3 protein specific for macrophages was observed in abdominal aorta of ang II treated animals, but over expression of CD45.1 & 45.2 proteins specific to lymphocytes were observed in high fat diet group. Based on our observations, Ang II induced aortic aneurysm by recruiting/ proliferating circulating monocytes by up regulating Icam-1, Vcam -1 and MCP-1. Also, ang II involved in degradation of elastin in the abdominal aorta by up regulation of MMP2 to promote agranulocytes migration in the intimal layers. Epithelial cell hyperplasia with accumulation of fatty fluids (cyst) was observed in seminal vesicle and ventral prostate of high fat treated animals. Fatty degeneration, germ cell apoptosis and infiltration giant cells were observed in the testes of high fat diet group. As per available literature these observations were not reported with high fat diet treatments with apo E models. High fat diet induced aneurysm prominently in abdominal, thoracic aorta and extensive plaque formation was observed in femoral and renal arteries. Administration of high fat diet containing cholesterol induced aneurysm in apo E mice model also efficient method to rule out the pathogenesis of aortic aneurysm when compared with angiotensin.