Hyperlipidemias: Yin W

Yin W, Tsutsumi K. · Department of Biochemistry and Molecular Biology, Medical School, Nanhua University, Hengyang 421001, China. · Cardiovasc Drug Rev. · Pubmed #12847564 No free full text.

Abstract: Lipoprotein lipase (LPL) is a rate-limiting enzyme that hydrolyzes circulating triglyceride-rich lipoproteins such as very low-density lipoproteins and chylomicrons. A decrease in LPL activity is associated with an increase in plasma triglycerides (TG) and a decrease in plasma high-density lipoprotein cholesterol (HDL-C). The increase in plasma TG and decrease in plasma HDL-C are risk factors for cardiovascular disease. Tsutsumi et al. hypothesized that elevating LPL activity would cause a reduction of plasma TG and an increase in plasma HDL-C, resulting in protection against the development of atherosclerosis. To test this hypothesis, Otsuka Pharmaceutical Factory, Inc. synthesized the LPL activator NO-1886. NO-1886 increased LPL mRNA and LPL activity in adipose tissue, myocardium and skeletal muscle, resulting in an elevation of postheparin plasma LPL activity and LPL mass in rats. NO-1886 also decreased plasma TG concentration and caused a concomitant rise in plasma HDL-C. Long-term administration of NO-1886 to rats and rabbits with experimental atherosclerosis inhibited the development of atherosclerotic lesions in coronary arteries and aortas. Multiple regression analysis suggested that the increase in plasma HDL-C and the decrease in plasma TG protect from atherosclerosis. The atherogenic lipid profile is changed to an antiatherogenic profile by increasing LPL activity, resulting in protection from atherosclerosis. Therefore, the LPL activator NO-1886 or other possible LPL activating agents are potentially beneficial for the treatment of hypertriglyceridemia, hypo-HDL cholesterolemia, and protection from atherosclerosis.

Yin W, Romeo S, Chang S, Grishin NV, Hobbs HH, Cohen JC. · Eugene McDermott Center for Human Growth and Development, Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8591, USA. · J Biol Chem. · Pubmed #19270337 links to  free full text

Abstract: Angiopoietin-like protein 4 (ANGPTL4) is a secreted protein that modulates the disposition of circulating triglycerides (TG) by inhibiting lipoprotein lipase (LPL). Here we examine the steps involved in the synthesis and post-translational processing of ANGPTL4, and the effects of a naturally occurring sequence variant (E40K) that is associated with lower plasma TG levels in humans. Expression of the wild-type and mutant proteins in HEK-293A cells indicated that ANGPTL4 formed dimers and tetramers in cells prior to secretion and cleavage of the protein. After cleavage at a canonical proprotein convertase cleavage site ((161)RRKR(164)), the oligomeric structure of the N-terminal domain was retained whereas the C-terminal fibrinogen-like domain dissociated into monomers. Inhibition of cleavage did not interfere with oligomerization of ANGPTL4 or with its ability to inhibit LPL, whereas mutations that prevented oligomerization severely compromised the capacity of the protein to inhibit LPL. ANGPTL4 containing the E40K substitution was synthesized and processed normally, but no monomers or oligomers of the N-terminal fragments accumulated in the medium; medium from these cells failed to inhibit LPL activity. Parallel experiments performed in mice recapitulated these results. Our findings indicate that oligomerization, but not cleavage, of ANGPTL4 is required for LPL inhibition, and that the E40K substitution destabilizes the protein after secretion, preventing the extracellular accumulation of oligomers and abolishing the ability of the protein to inhibit LPL activity.

Liu L, Ikeda K, Chen M, Yin W, Mizushima S, Miki T, Nara Y, Yamori Y. · Department of Neurobiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. · Clin Exp Pharmacol Physiol. · Pubmed #15649295 No free full text.

Abstract: 1. The aim of the present study was to investigate the trend of the prevalence of obesity in China and its association with hypertension and hypercholesterolemia. 2. A multicentre cross-sectional study was conducted in Chinese men and women aged 48-56 years between 1985 and 2000. In the report, three study periods were classified as survey 1 (1985), survey 2 (1988-1989) and survey 3 (1997-2000) in order to describe the long-term trend. 3. The results show that: (i) mean body mass index (BMI), prevalence of obesity (BMI > or = 28 kg/m2) and overweight (BMI > or = 25 and < 28 kg/m2) increased significantly from 1985 to 2000 in both sexes (P < 0.001); (ii) similar to the trend for BMI, the prevalence of hypertension and hypercholesterolaemia (total cholesterol (TC) > or = 220 mg/dL) also increased significantly from 1985 to 2000 (P < 0.001); (iii) partial correlation and multiple linear regression analyses indicated that increased BMI was significantly positively correlated with blood pressure and TC and negatively correlated with serum high-density lipoprotein-cholesterol (P < 0.01 or P < 0.001); and (iv) multiple logistics regression analysis models indicated that obese subjects had a 3.9-fold higher risk of being hypertensive (relative risk (RR) 4.9; 95% confidence interval (CI) 3.4-7.3) compared with those subjects who had a BMI less than 25 kg/m2. The corresponding RR (95% CI) of obesity for hypercholesterolaemia was 2.63 (1.57-4.40). 4. In conclusion, the results highlight the epidemic of obesity, an emerging risk in China. Great efforts must be made to alter this unwelcome trend.

Huang C, Yin W, Zeng G, Chen F. · School of Public Health, West China University of Medical Sciences, Chengdu 610041, China. · Wei Sheng Yan Jiu. · Pubmed #12712722 No free full text.

Abstract: Eighty seven subjects with abnormal blood glucose, blood pressure and serum triglycerides and cholesterol were selected. They are living in the urban area of Chengdu. Nutritional intervention measures included making suggestions on recipe, nutrition education and consultation etc. The following parameters were observed: 1. fasting blood glucose and postprandial blood glucose at 2 h after meal; 2. serum triglycerides and cholesterol; 3. blood pressure and body weight, and 4. symptom score. Data were analyzed by paired t-test, correlation and stepwise regression analysis. The results showed that above parameters were significantly improved by the end of the study. It can be considered that reasonable diet is a simple and effective measure to control these chronic diseases in communities.