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

Dietary fish oil containing the n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) is being consumed by many individuals in an effort to reduce thrombosis and heart disease. However, little is known about how these fatty acids can affect cerebrovascular function. The purpose of the present study was to begin to examine the effects of these fatty acids on cerebral arteriolar diameter and to compare their effects with that of arachidonic acid (AA). Pial arteriolar diameter responses to the topically applied fatty acids [0.2-200 micrograms/ml cerebrospinal fluid (CSF)] were measured in rabbits using in vivo microscopy and the acute cranial window technique. Prostaglandin E2 (PGE2) formed by the brain in response to AA, EPA, and DHA was measured in CSF using radioimmunoassay. EPA induced a dose-dependent dilation response of which the maximum was 29%, whereas the maximal dilation produced by AA was 100%. The arteriolar effect of EPA was reduced by indomethacin or superoxide dismutase plus catalase, indicating vasoactivity due to oxygen radicals formed by cyclooxygenase metabolism of EPA. DHA itself had no effect on diameter or adenosine-induced dilation but reduced dilation by AA when coapplied with AA. AA induced a 65-fold maximal increase in PGE2, whereas EPA and DHA had comparatively little effect. These results imply that substitution of n-3 fatty acids for AA in brain phospholipids may result in less cyclooxygenase-dependent cerebrovascular reactivity. This alteration in reactivity may produce important effects with respect to the brain's blood flow response to a number of physiological and pathological challenges.
 ...
PMID:Effect of fish oil n-3 fatty acids on cerebral microcirculation. 214 67

Reductions in dietary fat, saturated fat, and cholesterol have been recommended to reduce the risk of heart disease in our society. The effects of these modifications on human cytokine production and immune responses have not been well studied. 22 subjects > 40 yr of age were fed a diet approximating that of the current American (14.1% of calories as saturated fatty acids, [SFA], 14.5% monounsaturated fatty acids [MUFA], 6.1% [n-6] polyunsaturated fatty acids [PUFA], 0.8% [n-3] PUFA, and 147 mg cholesterol/1,000 calories) for 6 wk, after which time they consumed (11 in each group) one of the two low-fat, low-cholesterol, high-PUFA diets based on National Cholesterol Education Panel (NCEP) Step 2 recommendations (4.0-4.5% SFA, 10.8-11.6% MUFA, 10.3-10.5% PUFA, 45-61 mg cholesterol/1,000 calories) for 24 wk. One of the NCEP Step 2 diets was enriched in fish-derived (n-3) PUFA (low-fat, high-fish: 0.54% or 1.23 g/d eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] [121-188 g fish/d]) and the other low in fish-derived (n-3) PUFA (low-fat, low-fish [0.13% or 0.27 g/d EPA and DHA] [33 g fish/d]). Measurements of in vivo and in vitro indexes of immune responses were taken after each dietary period. Long-term feeding of low-fat, low-fish diet enriched in plant-derived PUFA increased blood mononuclear cell mitogenic response to the T cell mitogen Con A, IL-1 beta, and TNF production and had no effect on delayed-type hypersensitivity skin response, IL-6, GM-CSF, or PGE2 production. In contrast, the low-fat, high-fish diet significantly decreased the percentage of helper T cells whereas the percentage of suppressor T cells increased. Mitogenic responses to Con A and delayed-type hypersensitivity skin response as well as the production of cytokines IL-1 beta, TNF, and IL-6 by mononuclear cells were significantly reduced after the consumption of the low-fat, high-fish diet (24, 40, 45, 35, and 34%, respectively; P < 0.05 by two-tailed Student's t test except for IL-1 beta and TNF, which is by one-tailed t test). Our data are consistent with the concept that the NCEP Step 2 diet that is high in fish significantly decreases various parameters of the immune response in contrast to this diet when it is low in fish. Such alterations may be beneficial for the prevention and treatment of atherosclerotic and inflammatory diseases but may be detrimental with regard to host defense against invading pathogens.
 ...
PMID:Immunologic effects of national cholesterol education panel step-2 diets with and without fish-derived N-3 fatty acid enrichment. 832 75

The purpose of this double-blind study was to investigate the influence of dietary supplementation with an algae source of docosahexaenoic acid [DHA; 22:6(n-3)], devoid of any eicosapentaenoic acid [EPA; 20:5(n-3)], on serum/platelet DHA status, the estimated retroconversion of DHA to EPA, and risk factors for heart disease in vegetarian subjects. Healthy vegetarians (12 male, 12 female) consumed nine capsules daily of either DHA (1.62 g/d) or corn oil for 6 wk. Consumption of DHA capsules increased DHA levels in serum phospholipid by 246% (from 2.4 to 8.3 g/100 g fatty acids) and in platelet phospholipid by 225% (from 1.2 to 3.9 g/100 g fatty acids). EPA levels increased in serum phospholipid by 117% (from 0.57 to 1.3 g/100 g fatty acids) and in platelet phospholipid by 176% (0.21 to 0.58 g/100 g fatty acids) via metabolic retroconversion; the estimated extent of DHA retroconversion to EPA was 11.3 and 12.0%, based on the serum and platelet analyses, respectively. Arachidonic acid [AA; 20:4(n-6)] levels in serum and platelet phospholipids decreased moderately during the trial period (DHA group) as did both docosapentaenoic acids [22:5(n-6) and 22:5(n-3)]. Although no significant changes were found in the total and LDL-cholesterol levels with DHA supplementation, the total cholesterol:HDL-cholesterol ratio showed a moderate decrease over time as did the LDL-cholesterol:HDL-cholesterol ratio and serum triglyceride concentrations. DHA supplementation did not alter the various thrombogenic factors measured. In conclusion, DHA supplementation markedly enhanced the DHA status (of serum and platelets), provided for the formation of substantial EPA, and lowered the total and LDL-cholesterol:HDL-cholesterol ratios.
 ...
PMID:Supplementation with an algae source of docosahexaenoic acid increases (n-3) fatty acid status and alters selected risk factors for heart disease in vegetarian subjects. 900 71

Fish consumption has been shown to influence epidemiology of heart disease, and garlic has been shown to influence triglyceride levels. This study was undertaken to evaluate the effect of fish oil and garlic combinations as a dietary supplement on the lipid subfractions. Forty consecutive subjects with lipid profile abnormalities were enrolled in a single-blind, placebo-controlled crossover study. Each subject received placebo for 1 month and fish oil (1800 mg of eicosapentanoic acid [EPA] + 1200 mg of docosahexanoic acid) with garlic powder (1200 mg) capsules daily for 1 month. Lipid fractionation was performed prior to study initiation, after the placebo period, and after the intervention period. Subjects all had cholesterol levels > 200. Subjects were instructed to maintain their usual diets. Supplementation for 1 month resulted in an 11% decrease in cholesterol, a 34% decrease in triglyceride, and a 10% decrease in low-density lipoprotein (LDL) levels, as well as a 19% decrease in cholesterol/high-density lipoprotein (HDL) risk. Although not significant, there was a trend toward increase in HDL. There was no significant placebo effect. These results suggest that in addition to the known anticoagulant and antioxidant properties of both fish oil and garlic, the combination causes favorable shifts in the lipid subfractions within 1 month. Triglycerides are affected to the largest extent. The cholesterol lowering and improvement in lipid/HDL risk ratios suggests that these combinations may have antiatherosclerotic properties and may protect against the development of coronary artery disease.
 ...
PMID:Modulation of lipid profile by fish oil and garlic combination. 934 81

The offspring of coronary heart disease (CHD) patients are at particularly high risk for developing CHD. Endothelial dysfunction is present in the majority of CHD and atherosclerosis patients. Fish oil, rich in n-3 fatty acids has been shown to augment endothelium-dependent vasodilatation in human peripheral and coronary arteries. The aims of this study are to investigate presence of endothelial dysfunction determined by the brachial flow-mediated diameter, nitric oxide, plasma lipids and fibrinogen, and the effect of high doses of fish oil on these parameters. Twenty-four healthy offspring of CHD patients (study group) were supplemented with 9 g/day Alsepa fish oil (each gram containing 180 mg EPA and 120 mg DHA), for a period of two weeks. Plasma nitric oxide, urine nitric oxide, fibrinogens and flow-mediated vasodilatation (FMD) were determined prior to fish oil therapy, two weeks into therapy and four weeks after the end of therapy with fish oil. Twelve healthy subjects (control group) with no family history of heart disease were studied as controls (day one only). The offspring had a lower increase in FMD and lower nitric oxide production, compared with the control group. No other parameters varied between the two groups. The administration of fish oil did not result in any changes in the studied parameters. In healthy offspring of CHD patients, early endothelial dysfunction was documented before evidence of atherosclerosis. Ingestion of fish oil over a 13-day period did not improve endothelial dysfunction.
 ...
PMID:Impaired nitric oxide production, brachial artery reactivity and fish oil in offspring of ischaemic heart disease patients. 1456 Jul 90

In the 2000 report of the National Research Council's Committee on the Toxicological Effects of Methylmercury (MeHg), various adverse health effects potentially associated with MeHg exposure including cardiovascular effects were considered. At that time, the committee concluded that neurodevelopmental toxicity was the most sensitive endpoint but recognized emerging evidence of potential cardiovascular effects at low levels of exposure. The committee recommended that these potential effects be addressed through the uncertainty factors applied to the development of the neurodevelopmental reference dose (RfD). This approach was adopted by the US EPA in its derivation of the methylmercury RfD. Since that time, additional studies have become available. The available studies addressing the broad categories of heart disease (including myocardial infarction (MI) and ischemic heart disease), hypertension, and heart rate variability are critically reviewed here. Overall, the evidence linking realistic rates of MeHg exposure from fish consumption to cardiovascular disease suggests an association with heart disease, particularly MI. The apparent antagonistic interaction of MeHg and n-3 fatty acids contained in fish suggests a causal mechanism. As different individuals and populations characteristically consume different species of fish, the risk of cardiovascular effects may not be a simple function of MeHg exposure but its assessment may well need to take n-3 fatty acid intake into account also. The case for significant adverse effects of MeHg on blood pressure at current levels of exposure is weaker. This effect, observed in childhood, does not appear to persist into adolescence, and animal studies are difficult to interpret given the high doses employed. The decrease in heart rate variability related to fetal exposure to MeHg in the same cohort appears to persist into early adolescence and may reflect developmental neurophysiological alterations that are consistent with the developmental neuropsychological effects also observed in that cohort. However, the cardiovascular significance of this effect with regard to its direct effect on health or its ability to predict other, more direct, health effects is unclear. At present, the studies of the Finnish cohort relating MeHg exposure to acute MI and coronary heart disease appear to provide the strongest basis for a formal quantitative risk assessment of the cardiovascular effects of MeHg.
 ...
PMID:A review of the studies of the cardiovascular health effects of methylmercury with consideration of their suitability for risk assessment. 1572 94

Exposure to environmental pollutants, such as polycyclic aromatic hydrocarbons (PAHs) found in coal tar mixtures and tobacco sources, is considered a significant risk factor for the development of heart disease in humans. The goal of this study was to determine the influence of PAHs present at a Superfund site on human coronary artery endothelial cell (HCAEC) phospholipase A(2) (PLA(2)) activity and apoptosis. Extremely high levels of 12 out of 15 EPA high-priority PAHs were present in both the streambed and floodplain sediments at a site where an urban creek and its adjacent floodplain were extensively contaminated by PAHs and other coal tar compounds. Nine of the 12 compounds and a coal tar mixture (SRM 1597A) activated group IVC PLA(2) in HCAECs, and activation of this enzyme was associated with histone fragmentation and poly (ADP) ribose polymerase (PARP) cleavage. Genetic silencing of group IVC PLA(2) inhibited both (3)H-fatty acid release and histone fragmentation by PAHs and SRM 1597A, indicating that individual PAHs and a coal tar mixture induce apoptosis of HCAECs via a mechanism that involves group IVC PLA(2). Western blot analysis of aortas isolated from feral mice (Peromyscus leucopus) inhabiting the Superfund site showed increased PARP and caspase-3 cleavage when compared to reference mice. These data suggest that PAHs induce apoptosis of HCAECs via activation of group IVC PLA(2).
 ...
PMID:Activation of group IVC phospholipase A(2) by polycyclic aromatic hydrocarbons induces apoptosis of human coronary artery endothelial cells. 2113 78

The epidemic of overweight and obesity around the world and in the US is a major public health challenge, with 1.5 billion overweight and obese adults worldwide, and 68% of US adults and 31% of US children and adolescents overweight or obese. Obesity leads to serious health consequences, including an increased risk of type 2 diabetes mellitus and heart disease. Current preventive and medical treatments include lifestyle modification, medication, and bariatric surgery in extreme cases; however, they are either not very efficacious or are very expensive. Obesity is a complex condition involving the dysregulation of several organ systems and molecular pathways, including adipose tissue, the pancreas, the gastrointestinal tract, and the CNS. The role of the CNS in obesity is receiving more attention as obesity rates rise and treatments continue to fail. While the role of the hypothalamus in regulation of appetite and food intake has long been recognized, the roles of the CNS reward systems are beginning to be examined as the role of environmental influences on energy balance are explored. Omega-3 polyunsaturated fatty acids are essential nutrients that play a beneficial role in several disease processes due to their anti-inflammatory effects, modulation of lipids, and effects on the CNS. Omega-3 fatty acids, specifically EPA and DHA, have shown promising preliminary results in animal and human studies in the prevention and treatment of obesity. Given their effects on many of the pathways involved in obesity, and specifically in the endocannabinoid and mesocorticolimbic pathways, we hypothesize that EPA and DHA supplementation in populations can reduce the reward associated with food, thereby reduce appetite and food intake, and ultimately contribute to the prevention or reduction of obesity. If these fatty acids do harbor such potential, their supplementation in many parts of the world may hold great promise in reducing the global burden of obesity.
 ...
PMID:Greasing the wheels of managing overweight and obesity with omega-3 fatty acids. 2198 5

Despite the Surgeon General's strong track record and the rapidly expanding body of solid scientific work demonstrating that smoking caused a wide range of diseases, the decision making process for concluding "causality" in Surgeon General reports has become increasingly cautious and defensive. Whereas, the 1964 report did not conclude that smoking caused heart disease, it recommended that "from the public health viewpoint [one should] assume that the established association has causative meaning rather than to suspend judgment until no uncertainty remains," the de facto practice has become to do just the opposite. In particular, the 2004 report reached an affirmative negative conclusion that active smoking did not cause breast cancer and the 2006 report on passive smoking only found the link "suggestive." In contrast, in 2005 the California EPA found both active and passive smoking caused breast cancer in younger women. The evidence has continued to strengthen since 2005: there are now 12 large cohort studies that consistently demonstrate a dose-response relationship with smoking before first birth and increased breast cancer risk. The Surgeon General's increasing caution is preventing young women around the world from appreciating the risks that smoking and secondhand smoke pose for developing breast cancer.
 ...
PMID:The surgeon general report on smoking and health 50 years later: breast cancer and the cost of increasing caution. 2442 Sep 85

The medical community suffered three significant fish oil failures/setbacks in 2013. Claims that fish oil's EPA/DHA would stop the progression of heart disease were crushed when The Risk and Prevention Study Collaborative Group (Italy) released a conclusive negative finding regarding fish oil for those patients with high risk factors but no previous myocardial infarction. Fish oil failed in all measures of CVD prevention-both primary and secondary. Another major 2013 setback occurred when fish oil's DHA was shown to significantly increase prostate cancer in men, in particular, high-grade prostate cancer, in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) analysis by Brasky et al. Another monumental failure occurred in 2013 whereby fish oil's EPA/DHA failed to improve macular degeneration. In 2010, fish oil's EPA/DHA failed to help Alzheimer's victims, even those with low DHA levels. These are by no means isolated failures. The promise of fish oil and its so-called active ingredients EPA / DHA fails time and time again in clinical trials. This lipids-based physiologic review will explain precisely why there should have never been expectation for success. This review will focus on underpublicized lipid science with a focus on physiology.
...
PMID:Why fish oil fails: a comprehensive 21st century lipids-based physiologic analysis. 2538 31


1 2 Next >>