Preheparin serum lipoprotein lipase mass is negatively related to coronary atherosclerosis
Introduction
Lipoprotein lipase (LPL) catalyzes hydrolysis of triglycerides in circulating lipoproteins [1]. This enzyme is thought to be produced mainly in the adipose tissues and muscles and is transported to the surface of endothelial cells [2], [3]. It is then anchored to the surface of vascular endothelial cells. LPL analysis was conducted using postheparin plasma, because LPL is detached from the endothelial cells by heparin injection and is released into the blood stream [4]. Tornvall et al. [5] report that LPL mass exists in preheparin serum, even though lipase activity is scarcely detected. They also reported that this preheparin plasma LPL mass is detached from the endothelial surface after degradation and is transported to the liver to be cleared away. They observed a positive correlation between preheparin LPL mass and HDL cholesterol and a weak negative correlation with triglyceride in the patients with coronary artery diseases. We also observed similar results in people who had annual heath checks, and found that there was essentially no difference in preheparin LPL mass between men and women, and preheparin LPL mass was low in remnant-positive individuals [6]. Furthermore, administration of insulin sensitizer, troglitazone increased the preheparin LPL mass [7], indicating that preheparin LPL mass could reflect some of the LPL produced in a whole body, and may be related to insulin sensitivity. However, the real clinical significance of preheparin LPL mass has not yet been fully elucidated.
The artherogenic nature of triglyceride-rich lipoproteins such as remnants or intermediate density lipoproteins has recently been pointed out [8], [9]. Among possible mechanisms for the the retention of these triglyceride-rich lipoproteins, dysfunction of lipoprotein lipase is suggested [10], [11] in addition to the role of apolipoprotein E [12] and the receptors for remnants [13]. Tsutsumi et al. report that a novel compound No-1886, which enhances lipoprotein lipase expression, suppresses atherosclerotic lesions in the cholesterol-fed rat [14]. Shimada et al. [15] produced LPL transgenic mice and reported that these mice were resistant to progression of atherosclerotic lesion induced by cholesterol feeding. These studies suggest a possibility that enhanced LPL production may work as an anti-atherosclerotic factor.
In order to study the role of preheparin LPL mass in the progression of coronary atherosclerosis, we performed an angiographic study and compared preheparin LPL mass with other risk factors such as age, smoking, family history, hypertension, hyperuricemia, diabetes mellitus, serum lipids and obesity.
Section snippets
Subjects
The subjects were 70 men who were thought to have coronary artery disease (CAD) and who underwent coronary angiography after giving their informed consent at the Cardiovascular Center of Sakura Hospital, School of Medicine, Toho University. The average age was 57 years old (S.D., ±13), ranging from 22 to 79 years. Blood samples were drawn after fasting, just before heparin injection preceding coronary angiography. Portions necessary for LPL mass measurement were frozen at −80°C, within 1 h of
Preheparin LPL mass and serum lipid levels in all subjects taking coronary angiographical study
Negative correlation between preheparin LPL mass and triglycerides (R, −0.353, P<0.05) and positive correlation between preheparin LPL mass and HDL-cholesterol (R, 0.316, P<0.05) were observed (Fig. 1A and B). Significant correlations between preheparin LPL mass and total cholesterol or LDL-cholesterol were not observed (Fig. 1C and D).
The levels of preheparin LPL mass in the control group, the normal coronary group and the stenosis group
The levels of preheparin LPL mass were compared among three groups: the healthy control group, the normal coronary group and the coronary stenosis group. The
Discussion
In the cases studied, serum cholesterol levels of patients with coronary stenosis were similar to those in the Control and Normal Coronary groups, but triglyceride was mildly elevated and low HDL-cholesterol was observed (Table 1). These lipid profiles could be interpreted as the result the retention of triglyceride-rich lipoproteins such as very low density lipoproteins and/or remnants. This could be explained as being partly due to the clearance disturbance of triglyceride-rich lipoproteins
Acknowledgements
We are greatly indebted to Drs Kazuhito Mineoka, Takeshi Sakurai, Kaneyuki Aoyagi, Shin Satoh and Kunio Yoshinaga for their assistance in conducting CAG studies. This work was supported by the fund from the memorial 60th anniversary of Toho University, and also supported by Dai-ichi Pure Chemical. We also thank Professor Dr Hisao Tomioka M.D. for reviewing this manuscript.
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2017, Drug Discovery TodayIncreased postprandial apolipoprotein B-48 level after a test meal in diabetic patients: A multicenter, cross-sectional study
2016, Metabolism: Clinical and ExperimentalCitation Excerpt :The elevation of ApoB-48 would allow risk detection of CAD that might be underestimated by using other parameters. Impaired vascular state could affect the clearance of ApoB-48 containing triglyceride-rich particles because LPL is anchored to heparin sulfate proteoglycans on the luminal surface [27]: indeed, LPL mass was reduced in patients with atherosclerotic disease [28]. As shown in this study, diabetic patients showed increased ApoB-48 levels, so lipid management might be different from nondiabetic patients, and lipid-lowering therapy that inhibits absorption of cholesterol in the intestines, such as ezetimibe, might provide beneficial effects for the diabetic patients [29].