Spontaneous Atherosclerosis in Aged LCAT-Deficient Hamsters With Enhanced Oxidative Stress—Brief Report
| Autor: | Zongyu Liu, Yuhui Wang, Mengmeng Guo, Wei Huang, Xunde Xian, Mingming Gao, George Liu, Yitong Xu, Ping Ma |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Aortic Diseases medicine.disease_cause Animals Genetically Modified Phosphatidylcholine-Sterol O-Acyltransferase Gene Knockout Techniques chemistry.chemical_compound Lecithin Cholesterol Acyltransferase Deficiency Malondialdehyde Internal medicine medicine Animals Aorta Lipoprotein lipase Mesocricetus biology Atherosclerosis Lipids Plaque Atherosclerotic Disease Models Animal Oxidative Stress Endocrinology chemistry Lecithin—cholesterol acyltransferase biology.protein Female Cardiology and Cardiovascular Medicine Biomarkers Oxidative stress Lipoprotein |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 40:2829-2836 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Objective: LCAT (lecithin cholesterol acyltransferase) deficiency results in severe low HDL (high-density lipoprotein). Although whether LCAT is pro- or antiatherosclerosis was in debate in mouse studies, our previous study clearly shows that LCAT deficiency (LCAT −/− ) in hamster accelerates atherosclerotic development on high-fat diet. However, unlike in hypercholesterolemia and hypertriglyceridemia, whether LCAT deficiency could lead to spontaneous atherosclerosis has not been studied yet in animal models. We, therefore, sought to investigate the atherosclerosis in LCAT −/− hamsters on standard laboratory diet and explore the potential underlying mechanisms. Approach and Results: Young (16 months) male and female wild-type and LCAT −/− hamsters on standard laboratory diet were used. Compared with age- and sex-matched wild-type hamsters, LCAT −/− hamsters showed a complete loss of plasma HDL and an increase in triglyceride by 2- to 8-fold at different stages of age. In aged LCAT −/− hamsters, the lesion areas at the aortic roots were ≈40×10 4 μm 3 in males and 18×10 4 μm 3 in females, respectively, which were consistent with the en face plaques observed in male (1.2%) and (1.5%) female groups, respectively. The results of plasma malondialdehyde measurement showed that malondialdehyde concentrations were markedly elevated to 54.4 μmol/L in males and 30 μmol/L in females, which are significantly associated with the atherosclerotic lesions. Conclusions: Our study demonstrates the development of spontaneous atherosclerotic lesions in aged male and female LCAT −/− hamsters with higher plasma oxidative lipid levels independent of plasma total cholesterol levels, further confirming the antiatherosclerotic role of LCAT. |
| Databáze: | OpenAIRE |
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