The Role of DNA Double-strain Damage Repairing Mechanisms in Diabetic Atheroscolersis

ZENG Li, DING Qun-fang, XU Ting-yuan. et al

Abstract

To identify the role of DNA double-strain damage repairing pathway in the development of diabetics atherosclerosis. Methods Wistar male rats were randomly divided into three groups: control group (group A), balloon injury group (group B) and diabetes + balloon injury group (group C). Streptozotocin (STZ) was injected into rat abdomen to induce diabetes. After stabilizing high glucose, rats in group B and group C were both under aortic balloon injury technique and fed high lipid forage post-operatively. Glucose levels and weight were observed weekly. Segments of aortoa of three groups were taken at 2, 4, 6 and 8 weeks, staining of senescent β-galactosidase (SA-β-gal) staining, HE and changes of aorta under light microscope were observed. The area of tunica intima (I) and tunica media (M) in aorta was measured，and their ratio (I/M) were analyzed. Expressions of gamma-histong family 2A variant (γ-H2AX), phosphorylated ataxia telangiectasia mutated (ATM), phosphorylated checkpoint kinasen 2 (CHK2) and phosphorylated P53 were detected by immunohistochemical staining. Results SA-β-gal staining positive areas were dotted around in group B and group C [CM(155.3mm]but not in group A at two weeks.At the same time,a slight hyperlasia of aortic neointima was observed in HE staining of group B and group C. SA-β-gal staining was positive scattered within the tunica intima of aorta of group B and group C at four weeks, and HE staining promted a significantly greater of aortic neointima in the group C than that in the other two group (P <0.05). Positive regions of SA-β-gal staining were more in group C than group B at six weeks. Typical atherosclerotic plaques were formed, vascular smooth muscle cells were disordered arranged and foam cells were aggregated in the plaques of group C at six weeks post-operatively, and intimal membrane areas increased than group A and group B (P <0.05). At 8 weeks, SA-β-gal positive areas in group C were greater than in group B. The arteriolar wall was markedly thickened and the lumen was narrowed. The area of intimal membrane and the I/M radio were significantly greater in group C than those in group A and group B (P <0.05). Positive expressed of γ-H2AX, phosphorylated ATM, phosphorylated CHK2 and phosphorylated P53 were observed in typical atherosclerotic foci of group C, and weaker expressed in group B. Conclusion Cellular senescence of vascular edothelium is triggered and DNA double-strain damage is increased in diabetes. The DNA double-strain damage repairing machines may participate in the development of diabetic atherosclerosis.

 

Keywords: DNA double-strain damage repairing mechanisms, Cellular senescence, Diabetes, Atherosclerosis

 

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