Genetic Connection between Hyperglycemia and Carotid Atherosclerosis in Hyperlipidemic Mice.
Genetic Connection between Hyperglycemia and Carotid Atherosclerosis in Hyperlipidemic Mice.
复制标题
高脂血症小鼠高血糖与颈动脉粥样硬化之间的遗传联系。
DOI：
10.3390/genes13030510
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发表时间：
2022-03-14
期刊：
影响因子：
3.5
通讯作者：
Shi W
中科院分区：
文献类型：
--
作者：
Shi LJ;Chagari B;An A;Chen MH;Bao Y;Shi W
2型糖尿病（T2D）是动脉粥样硬化及其并发症的主要风险。Apoe-null（Apoe-/-）小鼠品系在对T2D和颈动脉粥样硬化的易感性方面表现出广泛的变化，后者是缺血性卒中的主要原因。为了确定T2D和颈动脉粥样硬化之间的遗传联系，从LP/J和BALB/cJ Apoe −/−小鼠中产生了145只雄性F2小鼠，并喂食12周的西方饮食。测量颈动脉粥样硬化病变、空腹和非空腹血糖水平，并使用miniMUGA阵列进行基因分型。在染色体（Chr）6和15上发现了颈动脉病变的两个显着QTL（数量性状基因座）。Chr15 QTL与QTL Bglu20在空腹和非空腹血糖水平上完全一致。颈动脉病变大小显示出与F2小鼠的空腹和非空腹血糖水平相关的趋势。排除空腹或非空腹血糖的影响后，颈动脉病变的Chr15 QTL被抑制。可能的候选基因为Tnfrsf11b、Deptor和Gsdmc 2。这些结果表明高血糖在高血糖小鼠颈动脉粥样硬化的发展中起着致病作用。
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.
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DOI：
10.1097/med.0000000000000321
发表时间：
2017-04
期刊：
Current opinion in endocrinology, diabetes, and obesity
影响因子：
--
作者：
Attie AD;Churchill GA;Nadeau JH
通讯作者：
Nadeau JH
DOI：
10.1161/01.atv.14.1.133
发表时间：
1994-01-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
作者：
NAKASHIMA, Y;PLUMP, AS;ROSS, R
通讯作者：
ROSS, R
影响因子：
3.3
作者：
Grainger, Andrew T.;Pilar, Nathanael;Shi, Weibin
通讯作者：
Shi, Weibin
影响因子：
5.3
作者：
PAIGEN, B;MORROW, A;HOLMES, P
通讯作者：
HOLMES, P
影响因子：
5.3
作者：
Fuller, Daniela T.;Grainger, Andrew T.;Shi, Weibin
通讯作者：
Shi, Weibin