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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperhomocysteinemia is a major and independent risk factor for vascular disease. Oxidative stress is a possible mechanism for homocysteine (Hcy)-induced endothelial dysfunction. Herein, we evaluated the antioxidant property of melatonin (MLT) in relation to the vasoconstrictive effect of Hcy on the human umbilical artery. In an initial experiment in a cell-free system, a micromolar concentration of iron was found to catalyze oxygen-dependent oxidation of Hcy. MLT (10 or 100 microM) did not affect oxygen-dependent oxidation of Hcy. Next, smooth muscle contraction induced by prostaglandin F(2alpha) (10 microM) was measured in arterial strips. Hcy (10 to 500 microM) increased this vascular tension in a concentration-dependent manner (P < 0.0001). Addition of Fe(2+) (10 microM) significantly potentiated the Hcy effect. Removal of endothelium (P < 0.05), pretreatment with a nitric oxide (NO) synthesis inhibitor (l-N(G)-monomethylarginine, 200 microM, P < 0.001), or pretreatment with a hydroxyl radical ((*)OH) scavenger (mannitol, 10 mM, P < 0.001) significantly attenuated contraction potentiated by Hcy plus Fe(2+). At a much lower concentration than mannitol, MLT (1 to 100 microM) significantly reduced the contractile effect of Hcy and Fe(2+) in a concentration-dependent manner. Hcy plus Fe(2+) significantly impaired calcium ionophore A 23187-induced relaxation (P < 0.0001), while MLT restored this relaxation in a concentration-dependent manner. These findings suggest that Hcy potentiates vascular tension in human umbilical artery, possibly by suppressing bioavailable NO. MLT protects against the vasoconstrictive effect of Hcy, most likely by scavenging (*)OH arising from Hcy autooxidation.
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PMID:Protective effect of melatonin against homocysteine-induced vasoconstriction of human umbilical artery. 1103 46

Geriatric population forms a significant proportion of our total population. Hence, various problems affecting the overall health of the elderly need special consideration. In this context, studies were undertaken to assess the socio-demographic factors, diet and health profile of 320 elderly men and women of all the three income groups of Urban Baroda. Data on socio-demographic factors was collected using an open ended questionnaire. Nutritional status was assessed using anthropometric measurements of height, weight, mid upper arm circumference (MUAC) and body mass index (BMI). Information on dietary profile was collected by 24 hour dietary recall method. Fasting practices were also studied. Socio-demographic data of geriatric men of high, middle and low income groups revealed that majority of the subjects were married. A greater percentage of high income group (HIG) men had nuclear family whereas majority of low income groups (LIG) elderly men resided in a joint family. Socio-demographic profile of elderly women of all the 3 income groups revealed that most of the subjects were Hindus. The percentage of widowhood, illiteracy and joint family system were higher in LIG as compared to the elderly women in middle and high income groups (MIG and HIG). Nutrient intake data of elderly men of all the income groups revealed lower consumption of energy, protein, iron and beta-carotene as compared to the RDA whereas fats and vitamin C intakes were higher as compared to the RDA (p < 0.05). The mean nutrient intake, by the LIG elderly women, in terms of energy, protein, iron, calcium, beta-carotene and vitamin C were significantly (p < 0.05) lower than the RDA as well as when compared to the elderly women of MIG and HIG. Mean anthropometric measurements of weight and BMI were higher in elderly HIG and MIG men as compared to the elderly men from LIG. Significant difference was found in all the anthropometric measurements of elderly women of LIG as compared to HIG and MIG. Morbidity profile showed a striking rise in problems of oral cavity, cardio vascular disease, neurological problems and problems of gastro intestinal tract with advancing age in both elderly men and women. The study reveals striking differences in diet, health and disease profile with advancing age.
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PMID:Diet nutrition and health profile of elderly population of urban Baroda. 1143 76

Myocardial infarction remains the No. 1 killer of American men and women, with a death rate of 225,000 per year, and stroke, the third leading cause of death in the United States, afflicts about 600,000 per year. The combined financial burden of these diseases is approximately $134 billion per year. Therefore, interventions that reduce mortality and suffering will have a significant impact on the health care system. This article summarizes research conducted during the last 2 decades that addresses the idea that stored iron plays a role in the pathogenesis of atherosclerosis and that iron reduction through phlebotomy may play a role in the treatment or prevention of atherosclerosis. Body iron stores rise after adolescence in men and menopause in women. This rise has been linked to the pathogenesis of atherosclerosis through iron-induced oxidation of low-density lipids and foam cell formation. However, the available evidence on the iron hypothesis remains circumstantial. Reduction of body iron stores in the setting of a controlled, prospective intervention trial is necessary to determine whether the amount of stored iron is related to clinically meaningful vascular disease. Such a study is feasible because reduction in iron stores can be achieved safely and predictably without induction of iron deficiency by graded phlebotomy. The Iron and Atherosclerosis Study (FeAST), a Veteran's Administration Cooperative Study, is under way to test this concept.
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PMID:Role of stored iron in atherosclerosis. 1199 91

In humans the iron status is influenced by environmental and genetic factors. Among them, the genetic polymorphism of the hemoglobin (Hb)-binding plasma protein haptoglobin (Hp) has been shown to affect iron turnover. The best known biological function of Hp is capture of free Hb in plasma to allow hepatic recycling of heme iron and to prevent kidney damage during hemolysis. In healthy males, but not in females, the Hp 2-2 phenotype is associated with higher serum iron, higher transferrin saturation, and higher ferritin than Hp 1-1 and 2-1. Moreover, serum ferritin correlates with monocyte L-ferritin content, which is also highest in Hp 2-2 subjects due to endocytosis of multimeric Hb-Hp 2-2 complexes by the recently identified Hb scavenger receptor CD163 in macrophages. This iron delocalization pathway, occurring selectively in Hp 2-2 subjects, has important biological and clinical consequences. The Hp polymorphism is related to the prevalence and the outcome of various pathological conditions with altered iron metabolism such as hemochromatosis, infections, and atherosclerotic vascular disease.
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PMID:Haptoglobin polymorphism and body iron stores. 1200 9

Gastrointestinal side effects were selected as the critical adverse effects on which to base the UL for iron. Although gastrointestinal distress is not a serious side effect when compared with the possible risk for vascular disease and cancer, the other side effects considered (impaired zinc absorption, increased risk for vascular disease and cancer, and systemic iron overload) did not permit the determination of a UL. Gastrointestinal distress is primarily observed in individuals who have consumed high levels of supplemental iron on an empty stomach. Large doses of iron supplements may inhibit zinc absorption when both are consumed in the fasting state, but zinc absorption is not impaired when supplementary iron is taken with meals. The relationship between iron intake and both vascular disease and cancer is unclear at the present time. With the possible exception of individuals living in Southern Africa who suffer from sub-Saharan iron overload, iron overload has not been shown to result solely from a high dietary iron intake. Moreover, no differences were found in the serum ferritin concentrations between individuals who fell in the lower and upper quartiles for total dietary iron intake in the Third National Health and Nutrition Examination Survey (NHANES 111) (Appendix Table H-5). Heterozygous carriers of the C282Y mutation most commonly associated with hereditary hemochromatosis could be at increased risk for accumulating harmful amounts of iron, but there are no direct observations to confirm this suspicion. Homozygotes and individuals with other iron-loading disorders may not be protected by the UL and are addressed under "Special Considerations".
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PMID:Iron: tolerable upper intake levels. 1245 26

Heme oxygenase (HO) catalyzes the degradation of heme to CO, iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although long considered irrelevant byproducts of heme catabolism, recent studies indicate that CO and the bile pigments biliverdin and bilirubin may play an important physiological role in the circulation. The release of CO by vascular cells may modulate blood flow and blood fluidity by inhibiting vasomotor tone, smooth muscle cell proliferation, and platelet aggregation. CO may also maintain the integrity of the vessel wall by directly blocking vascular cell apoptosis and by inhibiting the release of pro-apoptotic inflammatory cytokines from the vessel wall. These effects of CO are mediated via multiple pathways, including activation of soluble guanylate cyclase, potassium channels, p38 mitogen-activated protein kinase, or inhibition of cytochrome P450. In addition, the release of bile pigments may serve to sustain vascular homeostasis by protecting vascular cells from oxidative stress and by inhibiting the adhesion and infiltration of leukocytes into the vessel wall. Induction of HO-1 gene expression and the subsequent release of CO and bile pigments are observed in numerous vascular disorders and may provide an important adaptive mechanism to preserve homeostasis at sites of vascular injury. Thus, the HO-catalyzed formation of CO and bile pigments by vascular cells may function as a critical endogenous vasoprotective system. Moreover, pharmacological or genetic approaches targeting HO-1 to the vessel wall may represent a novel therapeutic approach in treating vascular disease.
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PMID:Carbon monoxide and bile pigments: surprising mediators of vascular function. 1255 43

Apolipoprotein E (apoE) is a multifunctional molecule that is active during brain development, maintenance, and injury. Allele epsilon 4 of apoE is recognized as a risk factor for beta-amyloidosis, but the responsible mechanisms are not clear. Recently, we showed that vascular smooth muscle cells (SMCs) from epsilon 4/ epsilon 4 carriers are the most susceptible to oxidative protein damage that was associated with the appearance of apoE-Abeta-immunoreactive granules in cells. Here, we demonstrate that apoE4 is more readily accumulated in SMCs treated with ferrous ions than is apoE3. ApoE accumulated in lysosomes in the form of monomers, dimers, apoE-containing complexes, and apoE fragments. ApoE4 and apoE4-containing complexes persisted in SMCs longer than apoE3 and its complexes. Both isoforms of apoE stimulated formation of apoE-Abeta deposits and increased immobilization of iron in cultures treated with ferrous ions. The accumulation of apoE-Abeta deposits in lysosomes was associated with the appearance of lipid peroxidation products such as malondialdehyde and 4-hydroxynonenal-2-nonenal. The higher cellular accumulation of apoE4 than apoE3 in SMCs exposed to oxidative stress may facilitate development of beta-amyloid angiopathy that is more frequent in epsilon 4/ epsilon 4 carriers.
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PMID:The effect of oxidative stress on accumulation of apolipoprotein E3 and E4 in a cell culture model of beta-amyloid angiopathy (CAA). 1291 65

Metals such as zinc, copper and iron contribute to aggregation of amyloid-beta (Abeta) protein and deposition of amyloid plaques in Alzheimer's disease (AD). We examined whether the lipophilic metal chelator DP-109 inhibited these events in aged female hAbetaPP-transgenic Tg2576 mice. Daily gavage administration of DP-109 for 3 months markedly reduced the burden of amyloid plaques and the degree of cerebral amyloid angiopathy in brains, compared to animals receiving vehicle treatment. Moreover, DP-109 treatment appeared to facilitate the transition of Abeta from insoluble to soluble forms in the cerebrum. These results further support the hypothesis that endogenous metals are involved in the deposition of aggregated Abeta in brains of AD patients, and that metal chelators may be useful therapeutic agents in the treatment of AD.
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PMID:The lipophilic metal chelator DP-109 reduces amyloid pathology in brains of human beta-amyloid precursor protein transgenic mice. 1546 29

Two children presented with acute hemiparesis 5 days and 3 weeks following varicella vaccination. Both showed unilateral infarction of the basal ganglia and internal capsule, a distribution consistent with varicella angiopathy. Both children had small patent foramen ovale (PFO), and one child also had severe iron-deficiency anemia, which may have predisposed the patient to this adverse effect.
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PMID:Stroke after varicella vaccination. 1558 Feb 16

We have recently demonstrated in multiple independent population-based longitudinal and cross sectional analyses that the haptoglobin 2-2 genotype is associated with an increased risk for diabetic cardiovascular disease. The chief function of haptoglobin (Hp) is to bind to hemoglobin and thereby prevent hemoglobin-induced oxidative tissue damage. This antioxidant function of haptoglobin is mediated in part by the ability of haptoglobin to prevent the release of iron from hemoglobin on its binding. We hypothesized that there may be diabetes- and haptoglobin genotype-dependent differences in the amount of catalytically active redox active iron derived from hemoglobin. We tested this hypothesis using several complementary approaches both in vitro and in vivo. First, measuring redox active iron associated with haptoglobin-hemoglobin complexes in vitro, we demonstrate a marked increase in redox active iron associated with Hp 2-2-glycohemoglobin complexes. Second, we demonstrate increased oxidative stress in tissue culture cells exposed to haptoglobin 2-2-hemoglobin complexes as opposed to haptoglobin 1-1-hemoglobin complexes, which is inhibitable by desferrioxamine by either a chelation or reduction mechanism. Third, we demonstrate marked diabetes-dependent differences in the amount of redox active iron present in the plasma of mice genetically modified expressing the Hp 2 allele as compared with the Hp 1 allele. Taken together these data implicate redox active iron in the increased susceptibility of individuals with the Hp 2 allele to diabetic vascular disease.
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PMID:Haptoglobin genotype- and diabetes-dependent differences in iron-mediated oxidative stress in vitro and in vivo. 1566 28


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