Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevated levels of homocysteine (Hcy) (known as hyperhomocysteinemia HHcy) are involved in dilated cardiomyopathy. Hcy chelates copper and impairs copper-dependent enzymes. Copper deficiency has been linked to cardiovascular disease. We tested the hypothesis that copper supplement regresses left ventricular hypertrophy (LVH), fibrosis and endothelial dysfunction in pressure overload DCM mice hearts. The mice were grouped as sham, sham + Cu, aortic constriction (AC), and AC + Cu. Aortic constriction was performed by transverse aortic constriction. The mice were treated with or without 20 mg/kg copper supplement in the diet for 12 weeks. The cardiac function was assessed by echocardiography and electrocardiography. The matrix remodeling was assessed by measuring matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMPs), and lysyl oxidase (LOX) by Western blot analyses. The results suggest that in AC mice, cardiac function was improved with copper supplement. TIMP-1 levels decreased in AC and were normalized in AC + Cu. Although MMP-9, TIMP-3, and LOX activity increased in AC and returned to baseline value in AC + Cu, copper supplement showed no significant effect on TIMP-4 activity after pressure overload. In conclusion, our data suggest that copper supplement helps improve cardiac function in a pressure overload dilated cardiomyopathic heart.
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PMID:Role of copper and homocysteine in pressure overload heart failure. 1867 30

Recent evidence suggests that higher doses of statins could improve clinical outcomes compared to conventional doses, but whether this benefit is due to "additional" pleiotropic effects is uncertain. We tested the hypothesis that atorvastatin 80 mg/day would have beneficial effects on indices of matrix remodelling (matrix metalloproteinase-1, MMP-1, and its tissue inhibitor, TIMP-1) in high-risk cardiovascular disease. We studied 27 "high-risk" patients (inclusion criteria: severe triple vessel but rejected for by-pass for extensive coronary disease, severe effort angina after coronary artery by-pass and premature coronary disease with > or =3 risk factors) with an abnormal lipid profile despite atorvastatin 40 mg/day, at baseline and at 3 months after increasing the statin dose to 80 mg/day. Baseline results in patients were compared to 22 healthy controls. At baseline, patients had lower levels of MMP-1 compared to controls. When atorvastatin was increased to 80 mg/day, significant reduction in LDL-cholesterol was observed, whereas MMP-1 and TIMP-1 levels were increased. These, despite of atorvastatin 40 mg daily, 'high-risk' patients still demonstrated abnormal extracellular remodelling indices. Doubling the dose of atorvastatin resulted in significant improvement in extracellular remodelling indices.
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PMID:Effects of atorvastatin 80 mg daily on indices of matrix remodelling in 'high-risk' patients with ischemic heart disease. 1732 Feb 12

Dietary very long chain omega (omega)-3 polyunsaturated fatty acids (PUFA) have been associated with reduced CVD risk, the mechanisms of which have yet to be fully elucidated. LDL receptor null mice (LDLr-/-) were used to assess the effect of different ratios of dietary omega-6 PUFA to eicosapentaenoic acid plus docosahexaenoic acid (omega-6:EPA+DHA) on atherogenesis and inflammatory response. Mice were fed high saturated fat diets without EPA and DHA (HSF omega-6), or with omega-6:EPA+DHA at ratios of 20:1 (HSF R=20:1), 4:1 (HSF R=4:1), and 1:1 (HSF R=1:1) for 32 weeks. Mice fed the lowest omega-6:EPA+DHA ratio diet had lower circulating concentrations of non-HDL cholesterol (25%, P<0.05) and interleukin-6 (IL-6) (44%, P<0.05) compared to mice fed the HSF omega-6 diet. Aortic and elicited peritoneal macrophage (Mphi) total cholesterol were 24% (P=0.07) and 25% (P<0.05) lower, respectively, in HSF R=1:1 compared to HSF omega-6 fed mice. MCP-1 mRNA levels and secretion were 37% (P<0.05) and 38% (P<0.05) lower, respectively, in elicited peritoneal Mphi isolated from HSF R=1:1 compared to HSF omega-6 fed mice. mRNA and protein levels of ATP-binding cassette A1, and mRNA levels of TNFalpha were significantly lower in elicited peritoneal Mphi isolated from HSF R=1:1 fed mice, whereas there was no significant effect of diets with different omega-6:EPA+DHA ratios on CD36, Mphi scavenger receptor 1, scavenger receptor B1 and IL-6 mRNA or protein levels. These data suggest that lower omega-6:EPA+DHA ratio diets lowered some measures of inflammation and Mphi cholesterol accumulation, which was associated with less aortic lesion formation in LDLr-/- mice.
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PMID:Reduction in dietary omega-6 polyunsaturated fatty acids: eicosapentaenoic acid plus docosahexaenoic acid ratio minimizes atherosclerotic lesion formation and inflammatory response in the LDL receptor null mouse. 1884 66

The aim of the study was to evaluate several mediators of inflammation in patients with aortic sclerosis in relation to severity of cardiovascular disease. Serum level of cytokines, soluble intracellular adhesion molecule 1, matrix metalloproteinase (MMP) 2 and 9 and their tissue inhibitor TIMP-1, were measured by ELISA and MMPs activity by zymography in 51 aortic sclerosis patients. The increase in MMPs expression positively correlated with their gelatinase activity; also there was a positive correlation between MMP-9 and TIMP-1 serum levels. Moreover, IL-6 concentration positively correlated with both serum level and activity of MMP-9. The level of IL-6 and IL-1Ra were higher in patients with a great burden of atherosclerosis. Noteworthy, statistically significant higher levels of IL-6 were noticed for patients with coronary artery disease. There was a significant increase in IL-6 serum level as well as a significant decrease in IL-1Ra for patients with a history of myocardial infarction. A trend toward higher concentration of inflammatory mediators was noticed in relation to the increase in severity of the aortic valve disease. Our results support the hypothesis of an "inflammatory pattern" associated with AS pathology and suggest the persistence of a chronic inflammation in patients who experienced acute coronary events.
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PMID:Systemic inflammatory markers in patients with aortic sclerosis. 1892 57

alpha-Linolenic acid (alphaLNA; 18: 3n-3) is essential in the human diet, probably because it is the substrate for the synthesis of longer-chain, more unsaturated n-3 fatty acids, principally EPA (20: 5n-3) and DHA (22: 6n-3), which confer important biophysical properties on cell membranes and so are required for tissue function. The extent to which this molecular transformation occurs in man is controversial. The present paper reviews the recent literature on the metabolism of alphaLNA in man, including the use of dietary alphaLNA in beta-oxidation, recycling of carbon by fatty acid synthesis de novo and conversion to longer-chain PUFA. Sex differences in alphaLNA metabolism and the possible biological consequences are discussed. Increased consumption of EPA and DHA in fish oil has a number of well-characterised beneficial effects on health. The present paper also reviews the efficacy of increased alphaLNA consumption in increasing the concentrations of EPA and DHA in blood and cell lipid pools, and the extent to which such dietary interventions might be protective against CVD and inflammation. Although the effects on CVD risk factors and inflammatory markers are variable, where beneficial effects have been reported these are weaker than have been achieved from increasing consumption of EPA+DHA or linoleic acid. Overall, the limited capacity for conversion to longer-chain n-3 fatty acids, and the lack of efficacy in ameliorating CVD risk factors and inflammatory markers in man suggests that increased consumption of alphaLNA may be of little benefit in altering EPA+DHA status or in improving health outcomes compared with other dietary interventions.
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PMID:Dietary alpha-linolenic acid and health-related outcomes: a metabolic perspective. 1907 74

Polyunsaturated fatty acids (PUFA) have a role in many physiological processes, including energy production, modulation of inflammation, and maintenance of cell membrane integrity. High plasma PUFA concentrations have been shown to have beneficial effects on cardiovascular disease and mortality. To identify genetic contributors of plasma PUFA concentrations, we conducted a genome-wide association study of plasma levels of six omega-3 and omega-6 fatty acids in 1,075 participants in the InCHIANTI study on aging. The strongest evidence for association was observed in a region of chromosome 11 that encodes three fatty acid desaturases (FADS1, FADS2, FADS3). The SNP with the most significant association was rs174537 near FADS1 in the analysis of arachidonic acid (AA; p = 5.95 x 10(-46)). Minor allele homozygotes had lower AA compared to the major allele homozygotes and rs174537 accounted for 18.6% of the additive variance in AA concentrations. This SNP was also associated with levels of eicosadienoic acid (EDA; p = 6.78 x 10(-9)) and eicosapentanoic acid (EPA; p = 1.07 x 10(-14)). Participants carrying the allele associated with higher AA, EDA, and EPA also had higher low-density lipoprotein (LDL-C) and total cholesterol levels. Outside the FADS gene cluster, the strongest region of association mapped to chromosome 6 in the region encoding an elongase of very long fatty acids 2 (ELOVL2). In this region, association was observed with EPA (rs953413; p = 1.1 x 10(-6)). The effects of rs174537 were confirmed in an independent sample of 1,076 subjects participating in the GOLDN study. The ELOVL2 SNP was associated with docosapentanoic and DHA but not with EPA in GOLDN. These findings show that polymorphisms of genes encoding enzymes in the metabolism of PUFA contribute to plasma concentrations of fatty acids.
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PMID:Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study. 1914 76

The aim of the present study was to verify whether plasma MMPs (matrix metalloproteinases) and TIMPs (tissue inhibitors of MMPs) could be used as potential markers of paraphysiological remodelling in the athlete's heart, and to correlate these matrix parameters with echocardiographic signs of LV (left ventricular) remodelling. Plasma MMP-2 and MMP-9 were measured by zymography, and TIMP-1 and TIMP-2 were measured by ELISA in 42 veteran marathoners with AH (athlete's heart), and in 25 sedentary healthy subjects (CTL). All subjects were submitted to a clinical examination and two-dimensional colour Doppler echocardiography together with the measurement of circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide); GGT (gamma-glutamyl transpeptidase) was evaluated as a marker of cardiovascular disease. Veteran athletes had a significant elevation in LV dimensions and calculated LV mass index. Diastolic and systolic functions were normal for both groups. MMP-9 levels were significantly lower in AH than in CTL subjects (56.9+/-4.3 compared with 119.4+/-21.5 m-units/l, P<0.01). There were significant differences in MMP-2 between the two groups, with a down-regulation in the AH subjects (182.5+/-16.8 units/ml in CTL compared with 117.1+/-9.1 units/ml in AH, P<0.01). MMP-2 and MMP-2/TIMP-2 were inversely correlated with myocardial indices of hypertrophy in AH and CTL subjects. AH and CTL subjects showed similar TIMP values. The results of the present study indicate that MMPs and TIMPs could represent potential biomarkers of adaptive heart remodelling in the athletes. In addition, the inverse correlation of the MMP-2/TIMP-2 system with echocardiographic signs of myocardial hypertrophy could represent a new diagnostic and prognostic indicator useful in the evaluation of cardiovascular risk in athletes.
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PMID:Role of matrix metalloproteinases and their tissue inhibitors as potential biomarkers of left ventricular remodelling in the athlete's heart. 1919 41

The amount and type of dietary fat have long been associated with the risk of CVD. Arterial stiffness and endothelial dysfunction are important risk factors in the aetiology of CHD. A range of methods exists to assess vascular function that may be used in nutritional science, including clinic and ambulatory blood pressure monitoring, pulse wave analysis, pulse wave velocity, flow-mediated dilatation and venous occlusion plethysmography. The present review focuses on the quantity and type of dietary fat and effects on blood pressure, arterial compliance and endothelial function. Concerning fat quantity, the amount of dietary fat consumed habitually appears to have little influence on vascular function independent of fatty acid composition, although single high-fat meals postprandially impair endothelial function compared with low-fat meals. The mechanism is related to increased circulating lipoproteins and NEFA which may induce pro-inflammatory pathways and increase oxidative stress. Regarding the type of fat, cross-sectional data suggest that saturated fat adversely affects vascular function whereas polyunsaturated fat (mainly linoleic acid (18 : 2n-6) and n-3 PUFA) are beneficial. EPA (20 : 5n-3) and DHA (22 : 6n-3) can reduce blood pressure, improve arterial compliance in type 2 diabetics and dyslipidaemics, and augment endothelium-dependent vasodilation. The mechanisms for this vascular protection, and the nature of the separate physiological effects induced by EPA and DHA, are priorities for future research. Since good-quality observational or interventional data on dietary fatty acid composition and vascular function are scarce, no further recommendations can be suggested in addition to current guidelines at the present time.
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PMID:Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function. 1924 68

Hypertriglyceridemia, regarded as one of the independent clinical markers of metabolic syndrome, is a frequently observed disorder that has been shown to be common in the Arab region. Epidemiologic and clinical trials demonstrated that omega-3 fatty acids have the potential to reduce the incidence of cardiovascular disease (CVD); one of the mechanisms by which this effect is achieved is through reducing plasma triglyceride levels. There is strong scientific evidence from human trials that omega-3 fatty acids from either fish or fish oil supplements significantly reduce blood triglyceride levels and these benefits appear to be dose-dependent. The active ingredients of fish oils include the long chain fatty acids EPA and DHA. The ideal amount of omega-3 fatty acid that should be incorporated into the diet without provoking detrimental effects on other lipid components such as decreasing HDL-C and/or increasing LDL-C has not yet been elucidated. Presently, a prescription form of omega-3 fatty acid has been approved by the United States Food and Drug Administration (USFDA) as an adjunct to the diet for the treatment of very high triglyceride levels (> or = 500 mg/dl) in adults. Patients with hypertriglyceridemia have been shown to respond well to the use of omega-3 fatty acids even when used in conjunction with statins where greater improvements in the lipid profile were found as compared to treatment with statins alone. A determinant of the responsiveness to fish oil could be attributed to the ApoE genotype of individuals.
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PMID:Fish oil and the management of hypertriglyceridemia. 1932 19

High sensitivity C-reactive protein (hs-CRP) is a marker of low-grade sustained inflammation. Omega-3 (n-3) fatty acids have anti-inflammatory properties and are associated with reduced cardiovascular disease (CVD) risk. The aim of this study was to investigate whether plasma n-3 fatty acid concentration is related to hs-CRP concentration. A total of 124 free-living adults, were divided into tertiles of plasma hs-CRP (<1.0, 1.0-3.0 and >3.0 mg/l). Body composition and anthropometric measurements were recorded. Hs-CRP was analysed using immunoassays and fatty acids were measured by gas chromatography. Plasma hs-CRP concentration was negatively correlated with total n-3 fatty acids (P=0.05), eicosapentaenoic acid (EPA; P=0.002) and docosapentaenoic acid (DPA; P=0.01). The highest hs-CRP tertile (>3.0 mg/l) had significantly lower concentrations of total n-3 fatty acids, EPA and DPA, when compared with the other tertiles (P<0.05). This study provides evidence that in healthy individuals, plasma n-3 fatty acid concentration is inversely related to hs-CRP concentration, a surrogate marker of CVD risk.
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PMID:An inverse relationship between plasma n-3 fatty acids and C-reactive protein in healthy individuals. 1935 79


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