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实验性高胆固醇血症早期冠状动脉病变中的c-myc激活

c-myc activation in early coronary lesions in experimental hypercholesterolemia.

作者信息

de Nigris F, Lerman L O, Rodriguez-Porcel M, De Montis M P, Lerman A, Napoli C

机构信息

Department of Medicine, University of Naples, Naples, 80131, Italy.

出版信息

Biochem Biophys Res Commun. 2001 Mar 9;281(4):945-50. doi: 10.1006/bbrc.2001.4431.

DOI:10.1006/bbrc.2001.4431
PMID:11237752
Abstract

This study tested the hypothesis that c-Myc activation, an oxidation-sensitive transcription factor, and its binding partner Max occurs in coronary arteries of hypercholesterolemic (HC) pigs, and can be attenuated by chronic antioxidant intervention. Coronary arteries were isolated from normal, HC pigs, or HC supplemented with antioxidant vitamins (HC + vitamins). The expression of the c-Myc/Max complex, and its target genes GADD45 and p53, was studied in nonatherosclerotic, early lesions (LL), positively staining for oil-red-O, in adjacent lesion-prone regions (PL), and in healthy segments (HV). The expression of c-Myc and Max in HC was 2- to 3-fold greater in PL, and 4-fold in LL, compared to normal vessels (P < 0.01). The expression of GADD45 was down-regulated, and of p53 increased, in the same regions. These alterations were attenuated in the HC + vitamins. Thus, c-Myc activation is an early atherosclerosis, in both PL and LL coronary arterial regions, and can be blunted by chronic dietary antioxidant intervention.

摘要

本研究检验了以下假设

c-Myc激活(一种氧化敏感的转录因子)及其结合伴侣Max存在于高胆固醇血症(HC)猪的冠状动脉中,并且慢性抗氧化剂干预可使其减弱。从正常猪、HC猪或补充抗氧化维生素的HC猪(HC + 维生素)中分离冠状动脉。在非动脉粥样硬化、早期病变(LL)、油红O阳性染色的相邻易损区域(PL)和健康节段(HV)中研究c-Myc/Max复合物及其靶基因GADD45和p53的表达。与正常血管相比,HC中PL区域的c-Myc和Max表达增加2至3倍,LL区域增加4倍(P < 0.01)。在相同区域,GADD45的表达下调,p53的表达增加。这些改变在HC + 维生素组中减弱。因此,c-Myc激活是PL和LL冠状动脉区域早期动脉粥样硬化的表现,并且慢性饮食抗氧化剂干预可使其减弱。

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