Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Controversy as to which lipoprotein subfraction of high-density lipoprotein (HDL) increases during alcohol consumption prompted the current study of the effects of two alcohol doses over varying time intervals on plasma lipoproteins and lipolytic enzymes. Measurements were made in 49 healthy men before and after three weeks of abstinence from alcohol and after consumption of one or three 12-ounce cans of beer per day. We found that HDL (10%), HDL2 (14%), and HDL3 (9%) cholesterol, and apolipoprotein A-I (7%) decreased with abstinence from alcohol and then increased with its consumption. These increases were not significant until after 3 weeks of daily alcohol intake, but they were significant in both the one-can and three-cans of beer per day groups. In the 23 inactive subjects HDL and HDL2 cholesterol decreased with abstinence but did not increase significantly with alcohol intake. Lipolytic enzymes were not changed by alcohol manipulation, but the level of lipoprotein lipase was higher and that of hepatic lipase was lower at each measurement point in the 26 habitually active versus the 23 inactive subjects. Adjustment for weight or skinfold thickness did not affect lipoprotein changes over time within groups but did eliminate many of the differences between activity groups. Alcohol consumption seems to be related to possibly beneficial influences on plasma HDL and HDL2 cholesterol, and may thus impact the risk of heart disease.
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PMID:Effect of alcohol dose on plasma lipoprotein subfractions and lipolytic enzyme activity in active and inactive men. 210 42

VLDL1, VLDL2, IDL, and LDL and its subfractions (LDL-I, LDL-II, and LDL-III) were quantified in 304 normolipemic subjects together with postheparin plasma lipase activities, waist/hip ratio, fasting insulin, and glucose. Concentrations of VLDL1 and VLDL2 rose as plasma triglycerides (TGs) increased across the normal range, but the association of plasma TGs with VLDL1 showed a steeper slope than that of VLDL2 (P < .001). Plasma TG level was the most important determination of LDL subfraction distribution. The least dense species, LDL-I, decreased as the level of this plasma lipid rose in the population. LDL-II in both men and women exhibited a positive association with plasma TG level in the range 0.5 to 1.3 mmol/L, increasing from about 100 to 200 mg/dL. In contrast, within this TG range the LDL-III concentration was low (approximately equal to 30 mg/dL) and changed little. As plasma TGs rose from 1.3 to 3.0 mmol/L there was a significant fall in LDL-II concentration in men (r = .45, P < .001) but not in women (r = .1, NS). Conversely, above the TG threshold of 1.3 mmol/L there was a steeper rise in LDL-III concentrations in men than in women (P < .001); 42% of the men had and LDL-III in the range associated with high risk of heart disease ( > 100 mg lipoprotein/dL plasma) compared with only 17% of the women. Other influences on the LDL subfraction profile were the activities of lipases and parameters indicative of the presence of insulin resistance. Men on average had twice the hepatic lipase activity of women. This enzyme was not strongly associated with variation in the LDL subfraction profile in men, but in women it was correlated with LDL-III (r = 39, P = .001) and remained a significant predictor in multivariate analysis. Increased waist/hip ratio, fasting insulin, and glucose were correlated negatively with LDL-I and positively with LDL-III, primarily, at least in the case of LDL-III, through raising plasma TGs. On the basis of these cross-sectional observations we postulate the following model for the generation of LDL-III. Subjects develop elevated levels of large TG-rich VLDL1 for a number of reasons, including failure of insulin action. The increase in the concentration of VLDL1 expands the plasma TG pool, and this, via the action of cholesteryl ester transfer protein (which facilitates neutral lipid exchange between lipoprotein particles), promotes the net transfer of TGs into LDL-II, the major LDL species.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Relations between plasma lipids and postheparin plasma lipases and VLDL and LDL subfraction patterns in normolipemic men and women. 758 63

Gynecologists are often responsible for the primary care of postmenopausal women. In this role, they become responsible for the assessment and subsequent management issues surrounding the prevention of atherosclerotic disease. The effects of estrogen upon the physiology of lipoproteins can be simplified to include an increased flux of apo B-100 particles out of and then back into the liver, an inhibition of hepatic lipase activity, and an apparent decrease in the hepatic secretion of lipoprotein(a) particles. In clinical practice, the lipoprotein picture is best thought of as one of a group of risk factors that need to be assessed and modified as needed, based upon the overall estimation of risk. The only caveat to this approach is that one should consider patients with proven heart disease for more aggressive therapy (to achieve an LDL cholesterol of less than 100 mg/dL), as long as there is no overriding morbidity from other causes.
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PMID:Lipids, atherosclerosis, and the postmenopausal woman. A clinical perspective. 793 48

In women, serum lipid levels and the incidence of myocardial ischemia increase after menopause. Deficiency of estrogen is believed to be the cause of these epidemiological phenomena. On the other hand, hormone replacement therapy(HRT), has prevailed in developed countries. Estrogen is replaced to ease climacteric disorders, and retard bone loss. Many clinical studies cleared the effect of HRT on lipids, in which total and LDL-C (cholesterol) decreased, and HDL-C increased. TG increased by conjugated equilin estrogen but not by transdermal estradiol. In our study, hepatic triglyceride lipase(HTGL) was suppressed by HRT, but lipoprotein lipase(LpL) was not suppressed. HRT decreases coronary artery diseases, but it is still controversial whether HRT is efficient in patients who already have heart disease.
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PMID:[Efficacy of hormone replacement therapy on hyperlipidemia]. 1063 24

Altered plasma levels of lipids and lipoproteins, obesity, hypertension, and diabetes are major risk factors for atherosclerotic cardiovascular disease. To identify genes that affect these traits and disorders, we looked for association between markers in candidate genes (apolipoprotein AII (apo AII), apolipoprotein AI-CIII-AIV gene cluster (apo AI-CIII-AIV), apolipoprotein E (apo E), cholesteryl ester transfer protein (CETP), cholesterol 7alpha-hydroxylase (CYP7a), hepatic lipase (HL), and microsomal triglyceride transfer protein (MTP)) and known risk factors (triglycerides (Tg), total cholesterol (TC), apolipoprotein AI (apo AI), apolipoprotein AII (apo AII), apolipoprotein B (apo B), body mass index (BMI), blood pressure (BP), leptin, and fasting blood sugar (FBS) levels.) A total of 1,102 individuals from the Pacific island of Kosrae were genotyped for the following markers: Apo AII/MspI, Apo CIII/SstI, Apo AI/XmnI, Apo E/HhaI, CETP/TaqIB, CYP7a/BsaI, HL/DraI, and MTP/HhpI. After testing for population stratification, family-based association analysis was carried out. Novel associations found were: 1) the apo AII/MspI with apo AI and BP levels, 2) the CYP7a/BsaI with apo AI and BMI levels. We also confirmed the following associations: 1) the apo AII/MspI with Tg level; 2) the apo CIII/SstI with Tg, TC, and apo B levels; 3) the Apo E/HhaI E2, E3, and E4 alleles with TC, apo AI, and apo B levels; and 4) the CETP/TaqIB with apo AI level. We further confirmed the connection between the apo AII gene and Tg level by a nonparametric linkage analysis. We therefore conclude that many of these candidate genes may play a significant role in susceptibility to heart disease.
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PMID:Candidate genes involved in cardiovascular risk factors by a family-based association study on the island of Kosrae, Federated States of Micronesia. 1211 31

A heritable deficiency of hepatic lipase (HL) provides insights into the physiologic function of HL in vivo. The metabolism of apolipoprotein B (apoB)-100 in very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) and of apoA-I and apoA-II in high-density lipoprotein (HDL) particles lipoprotein (Lp)(AI) and Lp(AI:AII) was assessed in 2 heterozygous males for compound mutations L334F/T383M or L334F/R186H, with 18% and 22% of HL activity, respectively, compared with 6 control males. Subjects were provided with a standard Western diet for a minimum of 3 weeks. At the end of the diet period, apo kinetics was assessed using a primed-constant infusion of [5,5,5-(2)H(3)] leucine. Mean plasma triglyceride (TG) and HDL cholesterol levels were 55% and 12% higher and LDL cholesterol levels 19% lower in the HL patients than control subjects. A higher proportion of apoB-100 was in the VLDL than IDL and LDL fractions of HL patients than control subjects due to a lower VLDL apoB-100 fractional catabolic rate (FCR) (4.63 v 9.38 pools/d, respectively) and higher hepatic production rate (PR) (33.24 v 10.87 mg/kg/d). Delayed FCR of IDL (2.78 and 6.31 pools/d) and LDL (0.128 and 0.205 pools/d) and lower PR of IDL (3.67 and 6.68 mg/kd/d) and LDL 4.57 and 13.07 mg/kg/d) was observed in HL patients relative to control subjects, respectively. ApoA-I FCR (0.09 and 0.13 pools/d) and PR (4.01 and 6.50 mg/kg/d) were slower in Lp(AI:AII) particles of HL patients relative to control subjects, respectively, accounting for the somewhat higher HDL cholesterol levels. HL deficiency may result in a lipoprotein pattern associated with low heart disease risk.
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PMID:Lipoprotein metabolism in subjects with hepatic lipase deficiency. 1504 2

Low levels of high density lipoprotein cholesterol (HDL-C) are an independent risk factor for coronary heart disease. The Turkish Heart Study revealed very low levels of plasma HDL-C in the Turkish population, a fact confirmed by the Heart Disease and Risk Factors in Turkish Adults study. Low HDL-C levels have also been observed in Turks living in the United States, Germany, and the Netherlands. Dietary habits do not explain the low HDL-C levels, which were found in Turkish Heart Study participants from six regions of Turkey with significant differences in typical diets. Among newborns and pre-pubescent children, plasma HDL-C levels were similar in Turks and western Europeans. After puberty, however, HDL-C levels declined significantly in Turkish boys and girls. These results suggest a genetic basis for the low HDL-C levels. In fact, hepatic lipase activity modulated by sex hormones was 25-30% higher in the Turkish population than in other populations. Elevated hepatic lipase activity is clearly associated with low plasma HDL-C in many studies. Results of a recent genome-wide scan for plasma HDL-C in Turks revealed a linkage on chromosome 15q22 where the hepatic lipase gene is located and that low HDL-C was 80% heritable. In addition, evidence for an interaction between HDL-C levels and modifiable environmental factors, particularly smoking and obesity, came from the study of cholesterol ester transfer protein TaqIB polymorphism. This polymorphism was associated with plasma HDL-C levels in Turks. Subjects with the B2B2 genotype-both smokers and nonsmokers-had higher plasma HDL-C levels. Interestingly, B2B2 subjects were protected from the HDL-C-lowering effect of smoking, whereas B1B1 subjects who smoked had significantly lower HDL-C levels. A similar interaction was observed between TaqIB polymorphism and obesity. In conclusion, low HDL-C levels in Turks were modulated by genetic factors and their interaction with modifiable environmental factors, such as smoking and obesity.
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PMID:Smoking and obesity make a bad problem worse: genetics and lifestyle affect high density lipoprotein levels in Turks. 1652 4

Cholesterol is not the only lipid that causes heart disease. Triglyceride supplies the heart and skeletal muscles with highly efficient fuel and allows for the storage of excess calories in adipose tissue. Failure to transport, acquire, and use triglyceride leads to energy deficiency and even death. However, overabundance of triglyceride can damage and impair tissues. Circulating lipoprotein-associated triglycerides are lipolyzed by lipoprotein lipase (LpL) and hepatic triglyceride lipase. We inhibited these enzymes and showed that LpL inhibition reduces high-density lipoprotein cholesterol by >50%, and hepatic triglyceride lipase inhibition shifts low-density lipoprotein to larger, more buoyant particles. Genetic variations that reduce LpL activity correlate with increased cardiovascular risk. In contrast, macrophage LpL deficiency reduces macrophage function and atherosclerosis. Therefore, muscle and macrophage LpL have opposite effects on atherosclerosis. With models of atherosclerosis regression that we used to study diabetes mellitus, we are now examining whether triglyceride-rich lipoproteins or their hydrolysis by LpL affect the biology of established plaques. Following our focus on triglyceride metabolism led us to show that heart-specific LpL hydrolysis of triglyceride allows optimal supply of fatty acids to the heart. In contrast, cardiomyocyte LpL overexpression and excess lipid uptake cause lipotoxic heart failure. We are now studying whether interrupting pathways for lipid uptake might prevent or treat some forms of heart failure.
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PMID:2017 George Lyman Duff Memorial Lecture: Fat in the Blood, Fat in the Artery, Fat in the Heart: Triglyceride in Physiology and Disease. 2941 10