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)

Matrix metalloproteinases (MMPs)/their inhibitors (TIMPs) system and elevated oxidative stress (SOX) have been implicated as important factors in atherosclerosis and vascular remodeling. The aim of the present study was to investigate whether MMPs/TIMPs system is associated with SOX in hemodialyzed (HD) patients. We compared the serum levels of metalloproteinases and their inhibitors, markers of SOX, inflammation and atherosclerosis between HD patients (n=40) with and without cardiovascular disease (CVD) and controls (n=20). Cu/Zn superoxide dismutase (Cu/Zn SOD) were elevated (all p<0.001), whereas total lipid peroxide levels were similar in HD patients and controls. The autoantibodies against oxidized LDL (OxLDL-Ab) levels were increased only in patients with CVD (p<0.05). Intima media thickness (IMT) in both CVD and in patients without CVD significantly exceeded those in the control (p<0.001 and p<0.01, respectively). Serum pre-HD values of MMP-2, TIMP-1 and TIMP-2 were significantly increased in HD patients, especially in the CVD group (all p<0.001), and they were associated with those of Cu/Zn SOD, IMT and CVD prevalence. Multiple regression analysis showed that MMP-2, Cu/Zn SOD levels and age independently and significantly predicted elevated IMT in HD patients. Our results suggest the association between SOX and the MMPs/TIMPs system in HD patients, which could represent one of the mechanisms involved in the progression of atherosclerosis in this population.
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PMID:Serum matrix metalloproteinase-2 and increased oxidative stress are associated with carotid atherosclerosis in hemodialyzed patients. 1651 Jan 49

The treatment of hyperlipidemia is aimed at preventing cardiovascular disease (CVD) and coronary heart disease (CHD). As the incidence of CHD in Japan is about one-third lower and that of stroke is two-fold higher compared to Western countries, and the doses of lipid-lowering drugs used in foreign randomized controlled clinical trials (RCTs) are much higher than in general use in Japan, it remains unclear whether the results of RCTs conducted in Western countries could be extrapolated to Japanese patients. Recently, two major large-scale, prospective, RCTs in Japanese hypercholesterolmic patients, the Management of Elevated Cholesterol in the Primary Prevention of Adult Japanese (MEGA) study and the Japan EPA Lipid Intervention Study (JELIS), have been reported. Japanese epidemiological studies and Japanese clinical studies are reviewed. The evidence suggests that hypercholesterolemia, hypertriglyceridemia, and low HDL-cholesterol are strongly associated with increased CHD risk. Lipid-lowering medication shows beneficial effects even in low-risk populations; however, the data did not support that lower cholesterol is better. The safety and efficacy of hyperlipidemia treatment in Japanese patients are discussed.
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PMID:Treatment of hyperlipidemia from Japanese evidence. 1719 91

Consumption of fish or fish oils rich in the n-3 long chain PUFA EPA and DHA may improve multiple risk factors for CVD. The objective of this study was to determine whether regular consumption of foods enriched with n-3 long-chain PUFA can improve n-3 long-chain PUFA status (erythrocytes) and cardiovascular health. Overweight volunteers with high levels of triacylglycerols (TG; >1.6 mmol/l) were enrolled in a 6-month dietary intervention trial conducted in Adelaide (n 47) and Perth (n 39), and randomised to consume control foods or n-3-enriched foods to achieve an EPA + DHA intake of 1 g/d. Test foods were substituted for equivalent foods in their regular diet. Erythrocyte fatty acids, plasma TG and other CVD risk factors were monitored at 0, 3 and 6 months. There were no significant differences between groups for blood pressure, arterial compliance, glucose, insulin, lipids, C-reactive protein (CRP) or urinary 11-dehydro-thromboxane B2 (TXB2) over 6 months, even though regular consumption of n-3-enriched foods increased EPA + DHA intake from 0.2 to 1.0 g/d. However, the n-3 long-chain PUFA content of erythrocytes increased by 35 and 53 % at 3 and 6 months, respectively, in subjects consuming the n-3-enriched foods. These increases were positively associated with measures of arterial compliance and negatively associated with serum CRP and urinary 11-dehydro-TXB2 excretion. Sustainable increases in dietary intakes and erythrocyte levels of n-3 long-chain PUFA can be achieved through regular consumption of suitably enriched processed foods. Such increases may be associated with reduced CV risk.
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PMID:Impact of foods enriched with n-3 long-chain polyunsaturated fatty acids on erythrocyte n-3 levels and cardiovascular risk factors. 1734 68

Matrix metalloproteinases (MMPs) have been implicated in the atherosclerotic process and risk factors for the disease such as hypertension, hyperlipidemia, or diabetes mellitus in adults. So far, circulating levels of MMPs and their tissue inhibitors (TIMPs) have not been assessed in children and adolescents with obesity, a known risk factor for cardiovascular disease. Plasma levels of MMP-9 and TIMP-1 were measured immunoenzymatically in 45 obese children and adolescents, aged 15 +/- 1.8 years. The control group consisted of 28 healthy children, aged 14.5 +/- 2.5 years. MMP-9 and TIMP-1 concentrations were higher in obese children than in the control group (MMP-9: 553.5 +/- 311 vs 400.4 +/- 204 ng/mL, respectively; P = .02; TIMP-1: 161.2 +/- 32 vs 143.1 +/- 20.1 ng/mL, respectively; P = .03). We found significantly higher levels of MMP-9 in obese children with coexisting hypertension than in obese normotensive patients (635 +/- 308 vs 450 +/- 289 ng/mL, respectively; P = .04). MMP-9 correlated with body mass index (BMI) (r = 0.33, P = .005) and fasting insulin (r = 0.3, P = .013); TIMP-1 correlated with BMI (r = 0.35, P = .006). In the group of obese hypertensive children (n = 25), MMP-9 correlated with BMI (r = 0.41, P = .001), systolic blood pressure (r = 0.41, P = .002), fasting insulin (r = 0.37, P = .006), and homeostasis model assessment index of insulin resistance (r = 0.27, P = .03). TIMP-1 correlated with BMI (r = 0.33, P = .025) and systolic (r = 0.38, P = .008) and diastolic (r = 0.47, P = .001) blood pressure. In the regression models, MMP-9 was found to be dependent on fasting insulin (R(2) = 0.16, P = .04), and TIMP-1 on BMI (R(2) = 0.14, P = .04). In the obese hypertensive group, TIMP-1 was dependent on diastolic blood pressure (R(2) = 0.18, P = .04). Obese children and adolescents have elevated plasma concentrations of MMP-9 and TIMP-1. Coexistence of hypertension may exacerbate alterations of extracellular matrix turnover in these patients. It might be hypothesized that elevated MMP and TIMP concentrations may be related to increased cardiovascular risk in obese and particularly in obese hypertensive children and adolescents.
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PMID:Elevated matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in obese children and adolescents. 1751 13

A higher proportion of n-3 long-chain PUFA in tissue lipids has been associated with a lower risk of CVD and some cancers. Diet is an important predictor of n-3 long-chain PUFA composition; however, the importance of non-dietary factors such as sex and age is unclear. We measured the proportion of n-3 long-chain PUFA in serum phospholipid, cholesterol ester and TAG of 2793 New Zealanders 15 years or older who participated in the 1997 National Nutrition Survey to determine differences by sex and age. Women had lower proportions of EPA and docosapentaenoic acid in phospholipid, by 0.07 (P = 0.004) and 0.10 (P < 0.001) mol%, respectively, and a higher proportion of DHA by 0.16 mol% (P = 0.001) compared with men. Intake of fish fat did not differ between men and women. There was a positive association between age and the proportion of EPA and DHA in phospholipid (P < 0.001). The sex differences in EPA and DHA were similar at all ages. Similar sex and age differences in serum cholesterol ester n-3 long-chain PUFA were found; only age differences were found in serum TAG. Sex and age differences in n-3 long-chain PUFA occur in the general population. Men and women may need to be considered separately when examining the association between disease risk and biomarkers of n-3 fatty acids.
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PMID:Serum n-3 long-chain PUFA differ by sex and age in a population-based survey of New Zealand adolescents and adults. 1767 66

Recent evidences suggest that modulation of vascular structure by matrix metalloproteinases (MMPs) could be a main determinant of acute cardiovascular events in high-risk subjects. The authors consecutively selected 46 subjects affected by familial combined hyperlipidemia (FCH), 44 by metabolic syndrome (MS), 44 by FCH and MS, and 40 healthy subjects. All these subjects were firstly diagnosed and not treated with lipid-lowering, antihypertensive, or antidiabetic drugs. A 12-h fasting blood sample was obtained from each patient, and plasma levels of MMP-2 and MMP-9 were measured together with their tissue inhibitors and a full set of laboratory cardiovascular disease markers. MMP-2 plasma levels were not significantly different among the considered groups. MMP-9, tissue inhibitor of MMP (TIMP)-1, and TIMP-2 are significantly higher in FCH (p < .001) and MS (p < .001) patients than in healthy controls, and they are also higher in MS patients than in FCH ones (p < .001). TIMP-1 (p < .001) and TIMP-2 (p < .001), but not MMP-9, are also significantly higher in subjects with MS associated to FCH than in patients with MS alone. No specific correlation among MMPs, TIMPs, and the other studied parameters has been observed in the whole sample and in the four above-defined subgroups. MMP-9, TIMP-1, and TIMP-2 plasma levels could be significant determinant and/or diagnostic markers of MS but not of FCH. However, the superposition of MS on FCH further increases the plasma level of these parameters. The prognostic value of this observation has to be evaluated.
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PMID:Vascular remodeling and prothrombotic markers in subjects affected by familial combined hyperlipidemia and/or metabolic syndrome in primary prevention for cardiovascular disease. 1792 35

The extracellular matrix is vital for maintaining tissue integrity, and the matrix metalloproteinases/tissue inhibitors of metalloproteinases (MMPs/TIMPs) system is involved in the regulation of extracellular matrix metabolism. Extracellular matrix turnover plays an important role in the change of large arterial mechanical properties in hypertension. However, the association of the metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP-9/TIMP-1) system and arterial stiffness is not straightforward and existing data are rather limited. Our objective is to explore the impact of the MMP-9/TIMP-1 system on large arterial stiffness in patients with essential hypertension. An automatic pulse wave velocity (PWV) measuring system was used to examine carotid-femoral PWV (CFPWV) and carotid-radial PWV (CRPWV) as the parameters reflecting central elastic large arterial and peripheral muscular medium-sized arterial elasticity, respectively; and serum MMP-9 and TIMP-1 levels, along with a number of other established biomarkers, were measured by enzyme-linked immunosorbent assay (ELISA) in 202 essential hypertensive patients and 54 age and gender-matched control subjects. Compared with the control subjects, hypertensive patients exhibited higher levels of MMP-9 (p=0.001) and TIMP-1 (p=0.002). Spearman's correlation analysis showed that serum levels of MMP-9 (p=0.014) and TIMP-1 (p=0.005) were significantly and positively correlated with CFPWV in hypertensive patients. A stepwise multiple regressive analysis demonstrated that age, systolic blood pressure, heart rate and TIMP-1 were independent predictors of CFPWV in patients with essential hypertension (adjusted r2=0.458). In conclusion, our results imply that the MMP-9/TIMP-1 system may play an important role in the determination of arterial function, and these findings may have implications for the involvement of MMP-9/TIMP-1 system in the pathophysiology of cardiovascular disease.
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PMID:Impact of the metalloproteinase-9/tissue inhibitor of metalloproteinase-1 system on large arterial stiffness in patients with essential hypertension. 1804 28

The most common omega-3 fatty acids contain 18-22 carbons and a signature double bond at the third position from the methyl (or n, or omega) end of the molecule. These fatty acids must be obtained in the diet as they cannot be synthesized by vertebrates. They include the plant-derived alpha-linolenic acid (ALA, 18:3n-3), and the fish-oil-derived eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). Normally, very little ALA is converted to EPA, and even less to DHA, and therefore direct intake of the latter two is optimal. EPA and DHA and their metabolites have important biologic functions, including effects on membranes, eicosanoid metabolism, and gene transcription. Studies indicate that the use of fish oil is associated with coronary heart disease risk reduction. A number of mechanisms may be responsible for such effects. These include prevention of arrhythmias as well as lowering heart rate and blood pressure, decreasing platelet aggregation, and lowering triglyceride levels. The latter is accomplished by decreasing the production of hepatic triglycerides and increasing the clearance of plasma triglycerides. Our focus is to review the potential mechanisms by which these fatty acids reduce cardiovascular disease risk.
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PMID:Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives. 1816 71

Dietary fish oil supplementation and regular physical activity can improve outcomes in patients with established CVD. Exercise has been shown to improve heart rate variability (HRV), a predictor of cardiac death, but whether fish oil benefits HRV is controversial. Obese adults at risk of future coronary disease have impaired HRV and may benefit from these interventions. We evaluated the effect of DHA-rich tuna fish oil supplementation with and without regular exercise on HRV in sedentary, overweight adults with risk factors for coronary disease. In a randomised, double-blind, parallel comparison, sixty-five volunteers consumed 6 g fish oil/d (DHA 1.56 g/d, EPA 0.36 g/d) or sunflower-seed oil (placebo) for 12 weeks. Half of each oil group also undertook regular moderate physical activity (3 d/week for 45 min, at 75 % of age-predicted maximal heart rate (HR)). Resting HR and the HR response to submaximal exercise were measured at weeks 0, 6 and 12. In forty-six subjects, HRV was also assessed by power spectrum analysis of 20 min electrocardiogram recordings taken supine at baseline and 12 weeks. Fish oil supplementation improved HRV by increasing high-frequency power, representing parasympathetic activity, compared with placebo (P = 0.01; oil x time interaction). It also reduced HR at rest and during submaximal exercise (P = 0.008; oil x time interaction). There were no significant fish oil x exercise interactions. Dietary supplementation with DHA-rich fish oil reduced HR and modulated HRV in keeping with an improved parasympathetic-sympathetic balance in overweight adults with risk factors for future coronary disease.
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PMID:Docosahexaenoic acid-rich fish oil improves heart rate variability and heart rate responses to exercise in overweight adults. 1833 22

The beneficial effects of long-chain (C chain >or=20) n-3 PUFA are well documented and, overall, increased intake reduces risk of CVD. Recent evidence also points to a role in reducing age-related decline in cognitive function. The two key fatty acids are EPA (20:5) and DHA (22:6), with current UK recommendation for adults being 450 mg EPA+DHA/d. Whilst some EPA and DHA can be synthesised in vivo from alpha-linolenic acid, recent data indicate this source to be very limited, suggesting that EPA and DHA should be classified as dietary essentials. In many parts of Europe the daily intake of EPA+DHA by adults and especially young adults (18-24 years) is <100 mg/d, since many never eat oily fish. Poultry meat contributes small but worthwhile amounts of EPA+DHA. Studies to enrich the EPA+DHA content of animal-derived foods mainly use fish oil in the diet of the animal. Recent work has shown that such enrichment has the potential to provide to the UK adult diet a daily intake of EPA+DHA of about 230 mg, with poultry meat providing the largest amount (74 mg). There are, however, concerns that the continued and possibly increased use of fish oils in animals' diets is not sustainable and alternative approaches are being examined, including the genetic modification of certain plants to allow them to synthesise EPA and DHA from shorter-chain precursors.
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PMID:Current intakes of EPA and DHA in European populations and the potential of animal-derived foods to increase them. 1849 71


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