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

The correlations between lipid and lipoprotein measurements and other risk factors of coronary artery disease were evaluated in 101 men undergoing coronary angiography. Clinically significant disease was present in 75 patients, whereas 24 had no observable lesions and 2 had minimal lesions. Comparisons of individual lipid and lipoprotein levels were nearly all significantly different between patients with and patients without clinically significant disease; however, no single variable could predict the presence of disease among patients. Logistic regression analysis identified five factors: apolipoprotein A-I, apolipoprotein B, diabetes, age, and family history of heart disease, which account for most of the differences between the two patient groups. These results could have important implications for the evaluation and management of patients suspected of having coronary atherosclerosis.
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PMID:Correlates of atherosclerosis in coronary arteries of patients undergoing angiographic evaluation. 211 60

Plasma levels of apolipoprotein A-I (apoA-I) are correlated with reduced incidence of heart disease due to the critical role of this protein in reverse cholesterol transport. Because of its diversity of function and poorly understood structure, much research has sought to understand how the structure of apoA-I facilitates its function. A popular approach has been the use of site-directed mutagenesis followed by structural and functional studies. There are a wide variety of expression systems available to produce these mutant proteins including eukaryotic cell lines and prokaryotic cells such as Escherichia coli. Expression in a bacterial system is generally favorable because it can produce large amounts of pure protein quickly and economically through the use of affinity tags on the expressed protein. Unfortunately, many of these systems are not ideal for the production of apolipoproteins because, in many cases, the proteolytic digestion required to remove the affinity tag also cleaves the target protein. Here we describe a method that produces large amounts of recombinant protein that is easily purified using a histidine (His) affinity tag that is cleaved with IgA protease from Neisseria gonorrhoeae. This enzyme does not cleave the wild type apoA-I sequence, leaving intact, mature apoA-I (containing a Thr-Pro- on the N-terminus). We show that this recombinant protein is similar to wild type protein in structure and function using circular dichroism analysis, lipid clearance assays, recombinant particle formation and cholesterol efflux assays. This system is particularly useful for the bacterial production of apolipoproteins because of the extreme specificity of IgA protease for its target cleavage site.
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PMID:Bacterial expression and characterization of mature apolipoprotein A-I. 1213 71

Apolipoproteins A-I and A-II form the major protein constituents of high-density lipid particles (HDL), the concentration of which is inversely correlated with the frequency of heart disease in humans. Although the physiological role of apolipoprotein A-II is unclear, evidence for its involvement in free fatty acid metabolism in mice has recently been obtained. Currently, the best characterized activity of apolipoprotein A-II is its potent antagonism of the anti-atherogenic and anti-inflammatory activities of apolipoprotein A-I, probably due to its competition with the latter for lipid acyl side chains in HDL. Many interactions of apolipoprotein A-I with enzymes and proteins involved in reverse cholesterol transport and HDL maturation are mediated by lipid-bound protein. The structural bases of interaction with lipids are expected to be common to exchangeable apolipoproteins and attributable to amphipathic alpha-helices present in each of them. Thus, characterization of apolipoprotein-lipid interactions in any apolipoprotein is likely to provide information that is applicable to the entire class. We report structures of human apolipoprotein A-II and its complex with beta-octyl glucoside, a widely used lipid surrogate. The former shows that disulfide-linked dimers of apolipoprotein A-II form amphipathic alpha-helices which aggregate into tetramers. Dramatic changes, observed in the presence of beta-octyl glucoside, might provide clues to the structural basis for its antagonism of apolipoprotein A-I. Additionally, excursions of individual molecules of apolipoprotein A-II from a common helical architecture in both structures indicate that lipid-bound apolipoproteins are likely to have an ensemble of related conformations. These structures provide the first experimental paradigm for description of apolipoprotein-lipid interactions at the atomic level.
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PMID:Structures of apolipoprotein A-II and a lipid-surrogate complex provide insights into apolipoprotein-lipid interactions. 3040 70

One of the American Heart Association's Top 10 Research Advances for the Treatment of Heart Disease is the use of a synthetic form of high-density lipoprotein (HDL) to reduce coronary atherosclerosis (JAMA. 2003;290:2292-2300). While HDL has not been a target for therapy for dyslipidemias, new insight into the major protein component of HDL, apolipoprotein A-I, may lead to new therapies. Apolipoprotein A-I was recently found to be a better predictor of cardiovascular events than is low-density lipoprotein (Am Heart J. 2003;146:227-233; J Intern Med. 2004;255:188-205). This article reviews the recent study by Nissen and colleagues describing the finding of a genetic mutation in HDL in some persons in Italy and the subsequent development of a synthetic form of HDL to be used as an infusion to successfully target atherosclerotic lesions (JAMA. 2003;290:2292-2300). In addition, controversies related to HDL cholesterol as a target for therapy are reviewed. Implications for nursing research, education, and practice are also described.
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PMID:A shot of good cholesterol: synthetic HDL, a new intervention for atherosclerosis. 1552 65

The transport of fat in the blood stream is approximately twice as fast in women as men. Disease states such as obesity and diabetes are associated with greater lipoprotein abnormalities in women compared with men. A greater increment in cardiovascular disease risk in women is linked to these abnormalities. A greater change in triglyceride level and a lesser change in low-density lipoprotein are observed in women than men with high-carbohydrate or high-fat feeding. Most consistent are greater changes in high-density lipoprotein (HDL), HDL2, and apolipoprotein A-I levels in women compared with men with high-carbohydrate or high-fat feeding. Dietary fat restriction in women appears to have a less beneficial lipoprotein effect than in men. Dietary fat restriction for heart disease prevention may be less ideal in women than in men.
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PMID:Gender differences in lipoprotein metabolism and dietary response: basis in hormonal differences and implications for cardiovascular disease. 1625 6

The transport of fat in the blood stream is approximately twice as fast in women as men. Disease states such as obesity and diabetes are associated with greater lipoprotein abnormalities in women compared with men. A greater increment in cardiovascular disease risk in women is linked to these abnormalities. A greater change in triglyceride level and a lesser change in low-density lipoprotein are observed in women than men with high-carbohydrate or high-fat feeding. Most consistent are greater changes in high-density lipoprotein (HDL), HDL(2), and apolipoprotein A-I levels in women compared with men with high-carbohydrate or high-fat feeding. Dietary fat restriction in women appears to have a less beneficial lipoprotein effect than in men. Dietary fat restriction for heart disease prevention may be less ideal in women than in men.
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PMID:Sex differences in lipoprotein metabolism and dietary response: basis in hormonal differences and implications for cardiovascular disease. 1705 98

A uniquely formulated soy phospholipid is being developed as a potential therapeutic for the treatment and prevention of heart disease. Three phase I and one phase I/II clinical trials have been completed with soy phosphatidylinositol (PI). The compound was shown to be safe in all trials and at doses over 5 g. Clinical studies have also shown early-stage efficacy to suggest that PI is able to raise plasma HDL-cholesterol and apolipoprotein A-I levels, and reduce triglyceride levels in humans. PI directly impacts plasma HDL levels through a MAPK stimulation of HDL production by the liver. Research has shown that the linoleic acid content of soy PI is critical to a peroxisome proliferator-activated receptor alpha dependent stimulation of HDL secretion. Soy-derived phospholipids uniquely affect cellular signaling and transcriptional processes. These lipids are safe and efficacious in humans and may therefore offer a novel therapeutic opportunity to treat cardiovascular disease.
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PMID:Phospholipids as cardiovascular therapeutics. 1831 64

Coronary heart disease is the leading cause of death in the USA and worldwide. Optimizing the ratio and levels of low- and high-density lipoproteins (HDLs) has been a major focus of treatments in preventing atherosclerosis. While these therapies have made significant contributions in reducing heart disease, many patients with normal lipid levels still continue to have significant coronary heart disease and crippling cardiac events. Recent research has brought to light the fact that HDL, widely touted to be protective against atherosclerosis, can actually promote atherogenesis in certain conditions. Disruption of anti-inflammatory properties of HDL may result in atherosclerosis in the presence of decreased, increased or unchanged serum HDL-cholesterol levels. The ability of HDL to prevent or promote atherogenesis can be assessed using a parameter termed the HDL inflammatory index. The next generation of emerging therapeutics, such as apolipoprotein A-I mimetic peptides, will be aimed at improving the anti-inflammatory property of HDL and thus further reducing the incidence of coronary heart disease.
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PMID:Oxidation hypothesis of atherogenesis: HDL inflammatory index and apolipoprotein A-I mimetic peptides. 1980 22

Human apolipoprotein A-I (apoA-I) is a 28kDa protein and a major component of high-density lipoproteins, mediating several essential metabolic functions related to heart disease. In the present study the potential protective role against bacterial pathogens was explored. ApoA-I suppressed bacterial growth of Escherichia coli and Klebsiella pneumoniae. The protein was able to bind lipopolysaccharides and showed a strong preference for bilayer vesicles made of phosphatidylglycerol over phosphatidylcholine. Lysine side chains of apoA-I were acetylated to evaluate the importance of electrostatic forces in the binding interaction with both membrane components. Electrophoresis properties, dot blot analysis, circular dichroism, and fluorescence spectroscopy to probe for changes in protein structure indicated that the acetylated protein displayed a strongly reduced lipopolysaccharide and phosphatidylglycerol binding. A mutant containing only the N-terminal domain of apoA-I also showed a reduced ability to interact with the membrane components, although to a lesser extent. These results indicate the potential for apoA-I to function as an antimicrobial protein and exerts this function through lysine residues.
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PMID:Apolipoprotein A-I binding to anionic vesicles and lipopolysaccharides: role for lysine residues in antimicrobial properties. 2345 85


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