Reduced high density lipoprotein cholesterol in severe hypertriglyceridemic ApoCIII transgenic mice via lowered hepatic ApoAI synthesis

High plasma triacylglycerol and low high-density lipoprotein levels are risk factors for cardiovascular disease in diabetes. Plasma high-density lipoprotein levels are regulated by cholesterol ester transfer protein (CETP). The regulation of CETP under diabetic conditions is not clear, and this is due to a lack of appropriate models. We used transgenic mice expressing human CETP to study the regulation of this protein under type-1 diabetic conditions and further investigated whether insulin reverses the effect of diabetes. Mice expressing human CETP under the control of its natural flanking region and age-matched littermates not expressing this protein were made diabetic by injecting streptozotocin, and the reversal of diabetes was assessed by injecting insulin. The plasma total cholesterol, low-density lipoprotein-cholesterol, and triacylglycerol concentrations were elevated, whereas high-density lipoprotein-cholesterol concentrations were reduced after the onset of diabetes. Insulin injection partially recovered this effect. The plasma cholesterol ester transfer activity, CETP mass, and hepatic CETP mRNA abundance were significantly higher in diabetic mice that were partially restored by insulin administration. There was a strong correlation between high-density lipoprotein-cholesterol concentrations and cholesterol ester transfer activity. These results suggest that an increase in CETP under diabetic conditions might be a major factor responsible for increased incidence of diabetes-induced atherosclerosis.Key words: transgenic mice, streptozotocin-induced diabetes, cholesterol ester transfer protein.

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Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)99088-5 ◽

1991 ◽

Vol 266 (17) ◽

pp. 10796-10801 ◽

Cited By ~ 14

Author(s):

L.B. Agellon ◽

A. Walsh ◽

T. Hayek ◽

P. Moulin ◽

X.C. Jiang ◽

...

Keyword(s):

Transgenic Mice ◽

High Density Lipoprotein ◽

Cholesteryl Ester ◽

Cholesteryl Ester Transfer Protein ◽

High Density Lipoprotein Cholesterol ◽

Density Lipoprotein ◽

High Density ◽

Lipoprotein Cholesterol ◽

Transfer Protein

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Triglyceride to high density lipoprotein cholesterol ratio, total cholesterol to high density lipoprotein cholesterol ratio and low ankle brachial index in an elderly population

VASA ◽

10.1024/0301-1526/a000348 ◽

2014 ◽

Vol 43 (3) ◽

pp. 189-197 ◽

Cited By ~ 10

Author(s):

Yiqiang Zhan ◽

Jinming Yu ◽

Rongjing Ding ◽

Yihong Sun ◽

Dayi Hu

Keyword(s):

High Density Lipoprotein ◽

Total Cholesterol ◽

High Density Lipoprotein Cholesterol ◽

Ankle Brachial Index ◽

Density Lipoprotein ◽

High Density ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Cholesterol Ratio ◽

Potential Biomarker

Background: The associations of triglyceride (TG) to high-density lipoprotein cholesterol ratio (HDL‑C) and total cholesterol (TC) to HDL‑C ratio and low ankle brachial index (ABI) were seldom investigated. Patients and methods: A population based cross-sectional survey was conducted and 2982 participants 60 years and over were recruited. TG, TC, HDL‑C, and low-density lipoprotein cholesterol (LDL-C) were assessed in all participants. Low ABI was defined as ABI ≤ 0.9 in either leg. Multiple logistic regression models were applied to study the association between TG/HDL‑C ratio, TC/HDL‑C ratio and low ABI. Results: The TG/HDL‑C ratios for those with ABI > 0.9 and ABI ≤ 0.9 were 1.28 ± 1.20 and 1.48 ± 1.13 (P < 0.0001), while the TC/HDL‑C ratios were 3.96 ± 1.09 and 4.32 ± 1.15 (P < 0.0001), respectively. After adjusting for age, gender, body mass index, obesity, current drinking, physical activity, hypertension, diabetes, lipid-lowering drugs, and cardiovascular disease history, the odds ratios (ORs) with 95 % confidence intervals (CIs) of low ABI for TG/HDL‑C ratio and TC/HDL‑C ratio were 1.10 (0.96, 1.26) and 1.34 (1.14, 1.59) in non-smokers. When TC was further adjusted, the ORs (95 % CIs) were 1.40 (0.79, 2.52) and 1.53 (1.21, 1.93) for TG/HDL‑C ratio and TC/HDL‑C ratio, respectively. Non-linear relationships were detected between TG/HDL‑C ratio and TC/HDL‑C ratio and low ABI in both smokers and non-smokers. Conclusions: TC/HDL‑C ratio was significantly associated with low ABI in non-smokers and the association was independent of TC, TG, HDL‑C, and LDL-C. TC/HDL‑C might be considered as a potential biomarker for early peripheral arterial disease screening.

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