Angiopoietin-like 2 has auxo-action in atherosclerosis by promoting atherosclerotic calcification

作者:Jiao, Lei; Zhuang, Yan; Jiang, Ming; Zhou, Jiao-Hao; Wu, Min*; Chen, Ze-Jun; Fang, Jing-Hai; Deng, Ying-Sheng
来源:International Journal of Clinical and Experimental Pathology, 2017, 10(8): 9084-9091.

摘要

Objective: To study the effects of angiopoietin-like 2 (Angptl2) on atherosclerotic calcification in aortic artery of ApoE(-/-) mice. Methods: Twelve 6-week-old male mice were randomly divided into control group (n=6) and interventional group (n=6), the control group were fed with high fat diet and the interventional group were fed with high fat diet and at the eighth week interventional group mice were infused (intravenously) with purified recombinant Angptl-2 once a week for one month. All mice were sacrificed when the mice were 16 weeks old, blood was collected and plasma triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDLC) were measured, aortic sections were stained with hematoxylin and eosin (HE) or Von Kossa and were observed under microscope. Calcium content and alkaline phosphatase activity of aorta were measured to measure the degree of vascular calcification. The expressions of Runx2 protein and mRNA levels in aortic sections of mice were detected by immunohistochemistry, Western Blot and qRT-PCR respectively. Results: The plasma TG, TC and LDLC level in interventional group was significantly higher than that in control group and the expression of Runx2 in aortic had the similar results. HE staining demonstrated significant thickening of the intima, with typical atherosclerotic plaque formation in interventional group mice, and Von Kossa staining showed spotty black clumps of aortic calcification under the fibrous cap plaque, while control group had atherosclerotic plaques without significant calcium deposits formation; The quantitative analysis showed that aortic vascular wall calcium and alkaline phosphatase activity were significantly higher in the intervention group than that of the control group (P<0.01). Conclusions: Angptl-2 could increase ApoE(-/-) mice plasma lipid level, it also facilitate the expression of Runx2, calcium content and ALP activity in aortic and then accelerate atherosclerotic calcification. Our experiments demonstrated that Angptl2 could accelerate atherosclerotic calcification. It reminded us that by controlling or decreasing the Anglt-2 level in plasma could help inhibit atherosclerotic calcification and then provides a new target to prevent coronary heart disease.