Phenotypic and Genetic Evidence for a More Prominent Role of Blood Glucose than Cholesterol in Atherosclerosis of Hyperlipidemic Mice
Hyperlipidemia and type 2 diabetes (T2D) are major risk factors for atherosclerosis. <i>Apoe</i>-deficient (<i>Apoe</i><sup>−/−</sup>) mice on certain genetic backgrounds develop hyperlipidemia, atherosclerosis, and T2D when fed a Western diet. Here, we sought to...
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MDPI AG
2022-08-01
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| author | Ashley M. Abramson Lisa J. Shi Rebecca N. Lee Mei-Hua Chen Weibin Shi |
| author_facet | Ashley M. Abramson Lisa J. Shi Rebecca N. Lee Mei-Hua Chen Weibin Shi |
| author_sort | Ashley M. Abramson |
| collection | DOAJ |
| description | Hyperlipidemia and type 2 diabetes (T2D) are major risk factors for atherosclerosis. <i>Apoe</i>-deficient (<i>Apoe</i><sup>−/−</sup>) mice on certain genetic backgrounds develop hyperlipidemia, atherosclerosis, and T2D when fed a Western diet. Here, we sought to dissect phenotypic and genetic relationships of blood lipids and glucose with atherosclerotic plaque formation when the vasculature is exposed to high levels of cholesterol and glucose. Male F2 mice were generated from LP/J and BALB/cJ <i>Apoe</i><sup>−/−</sup> mice and fed a Western diet for 12 weeks. Three significant QTL <i>Ath51</i>, <i>Ath52</i> and <i>Ath53</i> on chromosomes (Chr) 3 and 15 were mapped for atherosclerotic lesions. <i>Ath52</i> on proximal Chr15 overlapped with QTL for plasma glucose, non-HDL cholesterol, and triglyceride. Atherosclerotic lesion sizes showed significant correlations with fasting, non-fasting glucose, non-fasting triglyceride, and body weight but no correlation with HDL, non-HDL cholesterol, and fasting triglyceride levels. <i>Ath52</i> for atherosclerosis was down-graded from significant to suggestive level after adjustment for fasting, non-fasting glucose, and non-fasting triglyceride but minimally affected by HDL, non-HDL cholesterol, and fasting triglyceride. Adjustment for body weight suppressed <i>Ath52</i> but elevated <i>Ath53</i> on distal Chr15. These results demonstrate phenotypic and genetic connections of blood glucose and triglyceride with atherosclerosis, and suggest a more prominent role for blood glucose than cholesterol in atherosclerotic plaque formation of hyperlipidemic mice. |
| first_indexed | 2024-03-10T01:57:08Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:57:08Z |
| publishDate | 2022-08-01 |
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| spelling | doaj.art-b62d510a8d67488ca8ea702117dfbec52023-11-23T12:54:56ZengMDPI AGCells2073-44092022-08-011117266910.3390/cells11172669Phenotypic and Genetic Evidence for a More Prominent Role of Blood Glucose than Cholesterol in Atherosclerosis of Hyperlipidemic MiceAshley M. Abramson0Lisa J. Shi1Rebecca N. Lee2Mei-Hua Chen3Weibin Shi4Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22908, USADepartment of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22908, USADepartment of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22908, USADepartment of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22908, USADepartment of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22908, USAHyperlipidemia and type 2 diabetes (T2D) are major risk factors for atherosclerosis. <i>Apoe</i>-deficient (<i>Apoe</i><sup>−/−</sup>) mice on certain genetic backgrounds develop hyperlipidemia, atherosclerosis, and T2D when fed a Western diet. Here, we sought to dissect phenotypic and genetic relationships of blood lipids and glucose with atherosclerotic plaque formation when the vasculature is exposed to high levels of cholesterol and glucose. Male F2 mice were generated from LP/J and BALB/cJ <i>Apoe</i><sup>−/−</sup> mice and fed a Western diet for 12 weeks. Three significant QTL <i>Ath51</i>, <i>Ath52</i> and <i>Ath53</i> on chromosomes (Chr) 3 and 15 were mapped for atherosclerotic lesions. <i>Ath52</i> on proximal Chr15 overlapped with QTL for plasma glucose, non-HDL cholesterol, and triglyceride. Atherosclerotic lesion sizes showed significant correlations with fasting, non-fasting glucose, non-fasting triglyceride, and body weight but no correlation with HDL, non-HDL cholesterol, and fasting triglyceride levels. <i>Ath52</i> for atherosclerosis was down-graded from significant to suggestive level after adjustment for fasting, non-fasting glucose, and non-fasting triglyceride but minimally affected by HDL, non-HDL cholesterol, and fasting triglyceride. Adjustment for body weight suppressed <i>Ath52</i> but elevated <i>Ath53</i> on distal Chr15. These results demonstrate phenotypic and genetic connections of blood glucose and triglyceride with atherosclerosis, and suggest a more prominent role for blood glucose than cholesterol in atherosclerotic plaque formation of hyperlipidemic mice.https://www.mdpi.com/2073-4409/11/17/2669atherosclerosisdyslipidemiahyperglycemiaquantitative trait locustype 2 diabetes |
| spellingShingle | Ashley M. Abramson Lisa J. Shi Rebecca N. Lee Mei-Hua Chen Weibin Shi Phenotypic and Genetic Evidence for a More Prominent Role of Blood Glucose than Cholesterol in Atherosclerosis of Hyperlipidemic Mice Cells atherosclerosis dyslipidemia hyperglycemia quantitative trait locus type 2 diabetes |
| title | Phenotypic and Genetic Evidence for a More Prominent Role of Blood Glucose than Cholesterol in Atherosclerosis of Hyperlipidemic Mice |
| title_full | Phenotypic and Genetic Evidence for a More Prominent Role of Blood Glucose than Cholesterol in Atherosclerosis of Hyperlipidemic Mice |
| title_fullStr | Phenotypic and Genetic Evidence for a More Prominent Role of Blood Glucose than Cholesterol in Atherosclerosis of Hyperlipidemic Mice |
| title_full_unstemmed | Phenotypic and Genetic Evidence for a More Prominent Role of Blood Glucose than Cholesterol in Atherosclerosis of Hyperlipidemic Mice |
| title_short | Phenotypic and Genetic Evidence for a More Prominent Role of Blood Glucose than Cholesterol in Atherosclerosis of Hyperlipidemic Mice |
| title_sort | phenotypic and genetic evidence for a more prominent role of blood glucose than cholesterol in atherosclerosis of hyperlipidemic mice |
| topic | atherosclerosis dyslipidemia hyperglycemia quantitative trait locus type 2 diabetes |
| url | https://www.mdpi.com/2073-4409/11/17/2669 |
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