| Research Abstract |
High-density lipoprotein (HDL) is the anti-atherogenic lipoprotein that removes excess cholesterol from peripheral tissues an d transports it to the liver for the excretion. Epidemiological studies have clearly shown that low HDL-cholesterol level is as sociated with the high incidence of atherosclerotic disorders such as coronary artery disease (CAD). However, it is still controversial whether very high HDL-cholesterol level is favorable for the prevention of CAD. In this study, we examined the causes of hyper-α-lipoproteinemia (HAL) and its relation to atherosclerotic disorders. We obtained the following results ; (1) We determined the frequency of HAL (HDL-cholesterol【greater than or equal】100mg/dL) in 2,229 healthy subjects. HAL was found in 7 out of 1,033 men (0.7%), and 14 out of 1,196 women (1.2%), respectively. (2) We measured CETP mass in fasting serum from 83 HAL and control subjects. In men (n=26), the cholesteryl ester transfer protein (CETP) mass was significantly lower in
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HAL than in those with normal HDL-cholesterol level (1.6±0.6 vs. 2.2±0.5gμ/mL, p<0.001). In women (n=57), on the other hand, the CETP level was similar between HAL and control subjects (2.5±0.8 vs. 2.4±0.5 μg/mL). (3) Nondenaturing two-dimensional gel electrophoresis revealed that large- and medium-sized HDL with alpha-mobility (HDL2b, and HDL2a) were significantly higher in HAL subjects than in control subjects. It is noteworthy that prebetal-HDL, the initial acceptor of cellular cholesterol, also increased significantly in HAL. (4) Treadmill exercise electrocardiography was carried out in 42 (12 men and 30 women, aged 21-73 years) out of 83 HAL patients who were free from symptoms of ischemic heart disease. Although two patients (4.8%) showed significant ST depression during exercise, both of them were false positive. These results indicate that low CETP activity is more important in male HAL than in female HAL in Japan. Whether HAL promotes CAD remained to be determined in the future study. Less
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