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)

Porphyromonas gingivalis, a gram-negative anaerobe, is a major etiological agent in the initiation and progression of severe forms of periodontal disease. An opportunistic pathogen, P. gingivalis can also exist in commensal harmony with the host, with disease episodes ensuing from a shift in the ecological balance within the complex periodontal microenvironment. Colonization of the subgingival region is facilitated by the ability to adhere to available substrates such as adsorbed salivary molecules, matrix proteins, epithelial cells, and bacteria that are already established as a biofilm on tooth and epithelial surfaces. Binding to all of these substrates may be mediated by various regions of P. gingivalis fimbrillin, the structural subunit of the major fimbriae. P. gingivalis is an asaccharolytic organism, with a requirement for hemin (as a source of iron) and peptides for growth. At least three hemagglutinins and five proteinases are produced to satisfy these requirements. The hemagglutinin and proteinase genes contain extensive regions of highly conserved sequences, with posttranslational processing of proteinase gene products contributing to the formation of multimeric surface protein-adhesin complexes. Many of the virulence properties of P. gingivalis appear to be consequent to its adaptations to obtain hemin and peptides. Thus, hemagglutinins participate in adherence interactions with host cells, while proteinases contribute to inactivation of the effector molecules of the immune response and to tissue destruction. In addition to direct assault on the periodontal tissues, P. gingivalis can modulate eucaryotic cell signal transduction pathways, directing its uptake by gingival epithelial cells. Within this privileged site, P. gingivalis can replicate and impinge upon components of the innate host defense. Although a variety of surface molecules stimulate production of cytokines and other participants in the immune response, P. gingivalis may also undertake a stealth role whereby pivotal immune mediators are selectively inactivated. In keeping with its strict metabolic requirements, regulation of gene expression in P. gingivalis can be controlled at the transcriptional level. Finally, although periodontal disease is localized to the tissues surrounding the tooth, evidence is accumulating that infection with P. gingivalis may predispose to more serious systemic conditions such as cardiovascular disease and to delivery of preterm infants.
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PMID:Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis. 984 71

Iron supplementation has become an integral part of the management of patients receiving epoetin therapy, and clinicians have found it necessary to learn how and when to use it to the best advantage. Three routes of administration for iron are available: oral, intramuscular, and intravenous. Oral iron has the advantage of being simple and cheap, but it is limited by side-effects, poor compliance, poor absorption, and low efficacy. Intravenous iron is the best means of guaranteeing delivery of readily available iron to the bone marrow, but it requires greater clinical supervision. The i.v. iron preparations vary widely in their degradation kinetics, bioavailability, side-effect profiles, and maximum dose for single administration. Iron dextran is hampered by a small but significant risk of anaphylaxis, whereas all i.v. iron preparations can induce "free iron" reactions if the circulating plasma transferrin is overloaded. Intravenous iron may be given in advance of epoetin therapy, as concomitant treatment to prevent the development of iron deficiency, as treatment of absolute or functional iron deficiency, or as adjuvant therapy to enhance the response to epoetin in iron-replete patients. Markers of iron status that may indicate a need for i.v. iron include a serum ferritin of less than 100 microg/liter, a transferrin saturation of less than 20%, and a percentage of hypochromic red cells more than 10%. Various regimens are available for giving i.v. iron: low-dose administration of 20 to 60 mg every dialysis session in hemodialysis patients, medium-dose administration of 100 to 400 mg, and high-dose administration of 500 to 1000 mg. Iron sodium gluconate can only be given as a low-dose regimen because of toxicity, whereas the only preparation suitable for high-dose administration is iron dextran. Although concerns have been raised regarding iron overload and long-term toxicity with i.v. iron therapy in terms of increased risk of infections, cardiovascular disease, and malignancy, there is little evidence to substantiate this in patients receiving epoetin. Care should be taken, however, to prevent the serum ferritin rising above 800 to 1000 microg/liter and the transferrin saturation above 50%. Provided this is done, the benefits of i.v. iron almost certainly outweigh the risks in terms of optimizing the response to epoetin therapy.
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PMID:Strategies for iron supplementation: oral versus intravenous. 1008 88

Intensive iron therapy is now a generally accepted adjunct for the treatment of renal anemia with recombinant human erythropoietin. However, with the emerging role of iron in cardiovascular disease, carcinogenesis, infectious diseases, and other disorders, it is no longer appropriate to assume that any amount of stored iron is safe until proven otherwise. In this article, the history and current status of the "iron hypothesis" on ischemic heart disease are briefly reviewed, followed by comments on iron management practices for renal patients.
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PMID:Iron therapy and cardiovascular disease. 1008 98

Background-The genetic background of hereditary hemochromatosis (HH) is homozygosity for a cysteine-to-tyrosine transition at position 282 in the HFE gene. Heterozygosity for HH is associated with moderately increased iron levels and could be a risk factor for cardiovascular death. Methods and Results-We studied the relation between HH heterozygosity and cardiovascular death in a cohort study among 12 239 women 51 to 69 years of age residing in Utrecht, the Netherlands. Women were followed for 16 to 18 years (182 976 follow-up years). The allele prevalence of the HH gene in the reference group was 4.0 (95% CI 2.9 to 5.4). The mortality rate ratios for HH heterozygotes compared with wild types was 1.5 (95% CI 0.9 to 2.5) for myocardial infarction (n=242), 2.4 (95% CI 1.3 to 3. 5) for cerebrovascular disease (n=118), and 1.6 (95% CI 1.1 to 2.4) for total cardiovascular disease (n=530). The population-attributable risks of HH heterozygosity for myocardial infarction and cerebrovascular and total cardiovascular death were 3. 3%, 8.8%, and 4.0%, respectively. In addition, we found evidence for effect modification by hypertension and smoking. Conclusions-We found important evidence that inherited variation in iron metabolism is involved in cardiovascular death in postmenopausal women, especially in women already carrying classic risk factors.
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PMID:Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular death in women. 1049 67

Erythropoietin (EPO) therapy and appropriate iron administration are important aspects for managing the anemia of end-stage renal disease (ESRD). Achieving target hemoglobin levels of 11 to 12 g/dL and optimizing iron balance should improve clinical outcomes and increase patient quality of life. However, concerns have been raised about parenteral iron supplementation leading to excessively high iron levels, which may induce increased oxidative stress and risk for cardiovascular disease. Increased oxidative stress is often already present in patients with chronic renal disease and in patients with ESRD undergoing hemodialysis. The "iron hypothesis" proposes that excess iron is associated with increased risk for cardiac disease. While some studies have found an association between high iron levels or increased iron consumption with elevated risk for cardiac disease in subjects without renal disease, others have not found this association. Indeed, several studies suggest that achievement of target hematocrit levels in ESRD patients improves several clinical outcomes and that anemia itself is a risk factor for cardiac disease. Well-designed prospective studies are needed before the relationship between supplemental iron administration, excess iron, and cardiac disease can be firmly established.
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PMID:Iron and cardiac disease in the end-stage renal disease setting. 1051 71

One of the benefits of hormone replacement therapy (HRT) is to decrease cardiovascular disease. A mechanism whereby HRT may play a role in reducing cardiovascular risk is through improved iron status parameters. High serum ferritin has been related to increased risk of coronary heart disease, whereas low iron-binding capacity has been identified as an important risk factor for myocardial infarction. This study examined iron status parameters in a group of postmenopausal women taking oral HRT (n = 27) and those not taking oral HRT (n = 27) at two times 1 year apart. Women were compared on the following serum measures: estradiol, lipids, iron, total iron-binding capacity, and ferritin. Women taking HRT had higher levels of estradiol (p < 0.001) and improved lipid profiles (p < 0.001) (lower total and low-density lipoprotein [LDL] cholesterol and higher levels of high-density lipoprotein [HDL] cholesterol). In addition, women on HRT had better iron status parameters than those not on HRT (p = 0.002). Total iron-binding capacity was greater for women on HRT compared with women not on HRT, and serum ferritin levels were lower in women on HRT than those not on HRT. The groups were comparable in age, body mass index, and physical activity. Our results confirm previous findings and indicate that women taking HRT have higher serum levels of estradiol and improved lipid profiles compared with those not taking HRT. In addition, we have found that iron status parameters are better in women taking HRT, suggesting the need to further examine this effect as it relates to decreased cardiovascular risk in postmenopausal women.
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PMID:Improved iron status parameters may be a benefit of hormone replacement therapy. 1074 17

Scientific evidence is accumulating that meat itself is not a risk factor for Western lifestyle diseases such as cardiovascular disease, but rather the risk stems from the excessive fat and particularly saturated fat associated with the meat of modern domesticated animals. In our own studies, we have shown evidence that diets high in lean red meat can actually lower plasma cholesterol, contribute significantly to tissue omega-3 fatty acid and provide a good source of iron, zinc and vitamin B12. A study of human and pre-human diet history shows that for a period of at least 2 million years the human ancestral line had been consuming increasing quantities of meat. During that time, evolutionary selection was in action, adapting our genetic make up and hence our physiological features to a diet high in lean meat. This meat was wild game meat, low in total and saturated fat and relatively rich in polyunsaturated fatty acids (PUFA). The evidence presented in this review looks at various lines of study which indicate the reliance on meat intake as a major energy source by pre-agricultural humans. The distinct fields briefly reviewed include: fossil isotope studies, human gut morphology, human encephalisation and energy requirements, optimal foraging theory, insulin resistance and studies on hunter-gatherer societies. In conclusion, lean meat is a healthy and beneficial component of any well-balanced diet as long as it is fat trimmed and consumed as part of a varied diet.
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PMID:Dietary lean red meat and human evolution. 1091 88

Epidemiological studies have shown that the haemostatic parameters Fibrinogen (Fg), Factor VII (F VII), Factor VIII (F VIII), von Willebrand factor (vWF), Tissue Plasminogen Activator (t-PA), Plasminogen Activator Inhibitors (PAI) are risk factors/markers of ischemic cardiovascular disease. Ferritin (sFER) and Leukocytosis have also been implicated. In the present study we have followed the levels of fibrinogen, von Willebrand factor and thrombomodulin in relation to lipids, iron and the appearance of atherosclerotic lesions in New Zealand rabbits fed with a cholesterol enriched diet for a two-month period compared with a group of control rabbits. Hematocrit and white blood cell count (WBC) were measured in parallel. In hyperchlesterolemic rabbits the levels of fibrinogen and von Willebrand factor increased progressively, showing a positive correlation with the increasing cholesterol levels. There was an increase in soluble thrombomodulin beginning at the eighth week of study. In addition, these animals showed gross intimal atherosclerotic lesions in the whole extension of their aortas. Immunohistochemical studies showed the presence of fibrin(ogen) related antigen throughout the arterial wall and in the central portions of the atheromas. In the control group there was no formation of atherosclerotic plaques and all haemostatic, haematological and biochemical parameters were within the normal range. WBC and sFER levels were unaffected in both groups. Our results show that increased levels of fibrinogen and von Willebrand factor, known coronary risk factors, are strongly associated with the formation of atherosclerotic plaques in rabbits. The plaques contain a considerable amount of fibrinogen related antigen.
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PMID:Experimental thrombosis I: relation with fibrinogen and other haemostatic parameters. 1094 96

End-stage renal failure (ESRF) is associated with a higher risk of cardiovascular disease (CVD) than predicted by the major risk factors. We investigate the hypothesis that metalloproteins such as transferrin and ceruloplasmin and the inflammatory response are associated with CVD risk in this population. In this cross-sectional study of 81 subjects stable on haemodialysis (HD), 43 with CVD and/or peripheral vascular disease (PAD) were compared to 38 subjects without clinical evidence of CVD/PAD. Serum concentrations of metalloproteins and acute phase reactants were compared by univariate analysis and logistic regression modelling. Body mass index, gender ratios, prevalence of diabetes, iron status, and homocysteine concentrations did not differ significantly between the groups. Those with CVD were older (P< 0.001) and had been on dialysis for longer (P = 0.004). CVD subjects had significantly higher concentrations of ceruloplasmin (325 vs 284 mg/L, P = 0.011), copper (18.2 vs 15.7 micromol/L, P = 0.002), and C-reactive protein (CRP) (median 9.0 vs 3.8 mg/L, P = 0.002). Transferrin iron binding capacity tended to be higher in the CVD group (P = 0.088). CVD risk for subjects with serum concentrations in the upper tertile was increased 9.4-fold (CI 2.8-31.0) for copper, 4.2-fold (CI 1.5-12.2) for ceruloplasmin, 3.9-fold (CI 1.3-12.1) for transferrin iron binding capacity, and 2.3-fold (CI 0.9-6.1) for CRP. In multivariate logistic regression models, age (P = 0.001) and time on dialysis (P = 0.002) were the strongest risk factors for CVD. After adjustment for age and time on dialysis, transferrin iron binding capacity (P = 0.013) and copper (P = 0.019) continued to be associated with CVD risk but ceruloplasmin (P = 0.065) and CRP (P = 0.634) were not. Total cholesterol was associated with a lower risk of CVD (ie protective), presumably due to cholesterol-lowering therapy in high-risk patients. In conclusion, copper and transferrin iron binding capacity may be associated with CVD risk in HD subjects.
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PMID:Are metalloproteins and acute phase reactants associated with cardiovascular disease in end-stage renal failure? 1094 71

Haptoglobin is an acute phase protein capable of binding haemoglobin, thus preventing iron loss and renal damage. Haptoglobin also acts as an antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. There are 3 major haptoglobin phenotypes--Hp(1-1), Hp(2-1) and Hp(2-2). Possession of a particular phenotype has been associated with a variety of common disorders (e.g. cardiovascular disease, autoimmune disorders, malignancy), a fact which can only be explained by the idea that possession of a particular phenotype offers some protection against the development of these disorders. Knowledge of phenotype could therefore aid in the prognosis of disease and allow treatment to be better tailored to suit an individuals' needs.
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PMID:Haptoglobin: function and polymorphism. 1110 1


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