Genetic Connection between Hyperglycemia and Carotid Atherosclerosis in Hyperlipidemic Mice

Genes

Yongde Bao¹  Weibin Shi²  Mei-Hua Chen²  Lisa J. Shi²  Bilhan Chagari²  Alexander An² 

[1] Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA;Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22908, USA;

关键词: atherosclerosis;    carotid artery;    quantitative trait locus;    type 2 diabetes;    hyperlipidemia;   

DOI  :  10.3390/genes13030510

来源: DOAJ

【 摘 要 】

Type 2 diabetes (T2D) is a major risk for atherosclerosis and its complications. Apoe-null (Apoe^−/−) mouse strains exhibit a wide range of variations in susceptibility to T2D and carotid atherosclerosis, with the latter being a major cause of ischemic stroke. To identify genetic connections between T2D and carotid atherosclerosis, 145 male F2 mice were generated from LP/J and BALB/cJ Apoe^−/− mice and fed 12 weeks of a Western diet. Atherosclerotic lesions in the carotid arteries, fasting, and non-fasting plasma glucose levels were measured, and genotyping was performed using miniMUGA arrays. Two significant QTL (quantitative trait loci) on chromosomes (Chr) 6 and 15 were identified for carotid lesions. The Chr15 QTL coincided precisely with QTL Bglu20 for fasting and non-fasting glucose levels. Carotid lesion sizes showed a trend toward correlation with fasting and non-fasting glucose levels in F2 mice. The Chr15 QTL for carotid lesions was suppressed after excluding the influence from fasting or non-fasting glucose. Likely candidate genes for the causal association were Tnfrsf11b, Deptor, and Gsdmc2. These results demonstrate a causative role for hyperglycemia in the development of carotid atherosclerosis in hyperlipidemic mice.

【 授权许可】

Unknown