Abstract P065: Hypercholesterolemia Induced Atherosclerosis via the Mechanism of Autophagy Pathway
Objectives: To investigate the mechanism of hypercholesterolemia in the pathogenesis of atherosclerosis (AS).
Background: As the main risk factor of AS, the mechanism of hypercholesterolemia (HC) in the pathogenesis of AS remains unclear.
Methods: White New Zealand male rabbits were fed a high cholesterol diet (H) for 14 weeks to induce AS with normal diet fed rabbits as a control(N). In vitro, human aortic vascular endothelia (HAVED) and smooth muscle cells (HSMC) were incubated with different concentrations of HC in the comparison with the cells that the specific gene of Beclin1 or LC3-I/II were knocked down by siRNA transfection. Blood lipids, and vascular histologic structure, mRNA and protein expressions of Becline1, microtubule-associated protein 1 light chain 3(LC3-I/II) and autophagosomes were determined in the rabbit abdominal aorta or in the cultured cells.
Results: Serum levels of total cholesterol,triglyceride and low density lipoprotein cholesterol were significantly increased in H than those in N (P<0.05). Histologic structure of abdominal aorta showed more aggravated in wall thickness, lumen narrowness and atheroma in H than those in N (P<0.05). The expressions of Becline1, LC3-I/II in mRNA or proteins were strongly increased in H than those in N (P<0.05), which was consistent with the expressions of autophagosomes in the two groups.At the cap or the shoulder of atheromas, the expressions of Becline1, LC3-I/II and autophagosomes were far more enhanced than those in non-atheromatous areas in the same sample of H group (P<0.05). In vitro, HAVED or HSMC that preincubated with HC revealed more expressions of Becline1, LC3-I/II and autophagosomes, which were relevant to the concentrations and the preincubation time of HC, compared to the cells that incubated with N serum. Further, the autophagosomes in the cultured cells were correlated with the number of survive cells. Compared to the intact cells, the expressions of autophagosomes in the cells that the gene of Beclin1 or LC3-I/II was knocked down were greatly suppressed, and the number of survive cells was relatively increased, even they were exposed to HC incubation.
Conclusions: The current experiments suggested that HC mediated the pathogenesis of AS partially via the pathway of autophagy.
- © 2011 by American Heart Association, Inc.