Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heme oxygenase (HO) is a cytoprotective enzyme that degrades heme (a potent oxidant) to generate carbon monoxide (a vasodilatory gas that has anti-inflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron (sequestered by ferritin). Due to the properties of inducible HO (HO-1) and its products, we hypothesized that HO-1 would play an important role in the regulation of cardiovascular function. In this article we will review the role of HO-1 in cardiovascular function, and highlight our previous studies using gene deletion and gene overexpression transgenic approaches in mice. These studies will include the investigation of HO-1 in the setting of hypertension (renovascular), atherosclerosis and vascular injury (vein graft stenosis), hypotension (endotoxemia), and ischemia/reperfusion injury (heart). In a chronic renovascular hypertension model, blood pressure elevation, cardiac hypertrophy, acute renal failure, and acute mortality induced by one kidney-one clip surgery are more severe in HO-1 null mice. Moreover, absence of HO-1 leads to accelerated atherosclerotic lesion formation and vein graft disease. In addition, HO-1 null mice with endotoxemia have earlier resolution of hypotension, yet the mortality and the incidence of end organ damage are higher in the absence of HO-1. In contrast, mice with cardiac-specific overexpression of HO-1 have an improvement in cardiac function, smaller myocardial infarcts, and reduced inflammatory and oxidative damage after coronary artery ligation and reperfusion. Taken together, these studies suggest that an absence of HO-1 has detrimental consequences, while overexpression of HO-1 plays a protective role in ischemia/reperfusion injury.
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PMID:Role of heme oxygenase-1 in cardiovascular function. 1452 47

Heme oxygenase (HO), an enzyme essential for heme degradation, shows anti-oxidative and anti-inflammatory properties via the production of bile pigments, carbon monoxide (CO) and ferritin induction under various pathophysiological conditions. A number of recent studies have shown biological effects of HO reaction in cardiovascular disorders. An inducible form of HO, HO-1, is induced by a variety of stresses such as oxidized lipoproteins, cytokines, hemodynamic changes, angiotensin II and nitric oxide (NO) in vascular wall. HO-1 induction seems to function as an adaptive response against these injurious stimuli. HO-1 induction in artery wall scavenges reactive oxygen species, which leads to the attenuation of monocyte adhesion and chemotaxis. HO-1 induction also reduces lipid peroxidation in plasma and artery wall. These properties of HO-1 suggest anti-atherogenic roles of this enzyme. In this review, roles of endothelial HO-1 expression and bilirubin in atherogenesis are also discussed. HO-1 also seems to play a significant role in restenosis after angioplasty, which is a major clinical problem associated with atherosclerosis. Recent progress in human HO-1 genetics supports these experimental results. This review aims to reaffirm current problems in the biological aspects of HO and suggest future research direction and clinical application.
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PMID:Heme oxygenase-1 against vascular insufficiency: roles of atherosclerotic disorders. 1452 48

Cholesterol oxidation products, oxysterols, are thought to play a part in the initiation and development of human atherosclerotic lesions. Excessive body iron has been suggested to promote atherosclerosis and coronary heart disease through its pro-oxidative properties. In the present study, the associations between serum ferritin and plasma oxysterol concentrations were examined in 669 eastern Finnish men. Serum ferritin concentration had statistically significant (p <.05) direct correlations with most of the measured oxysterols. In multivariate adjusted regression models, serum ferritin concentration predicted significantly the levels of 27-hydroxycholesterol (beta = 0.13, p <.001), 7alpha-hydroxycholesterol (beta = 0.11, p =.005), 25-hydroxycholesterol (beta = 0.10, p =.007), 7-ketocholesterol (beta = 0.10, p =.009), and 7beta-hydroxycholesterol (beta = 0.10, p =.02). In conclusion, excess body iron, as assessed by serum ferritin, is associated with increased levels of circulating oxysterols, both of enzymatic and nonenzymatic origin, in man.
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PMID:Serum ferritin concentration is associated with plasma levels of cholesterol oxidation products in man. 1455 56

The aim of studies was a comparison of dialysis adequacy, nutritional parameters, results of the peritoneal equilibration test (PET) and selected standard clinical and laboratory data in peritoneal dialysis (PD) patients with different age, but comparable PD duration and outcome. Two groups of patients were examined: group I (n = 21, 9 F, 12 M) - age 67.7 +/- 4.5 yrs, PD duration 20.1 +/- 12.1 months; group II (n = 21, 9 F, 12 M) - age 42.8 +/- 9.1 yrs, PD duration 20.7 +/- 12.1 months. Parameters of PD adequacy, results of PET, markers of nutrition and standard laboratory measures were determined every 3 months to the end of PD treatment. First obtained values, mean values representing the entire PD course and last values obtained before the end of PD therapy were compared in group I and II. Differences in results obtained at the beginning and at the end of PD therapy were also compared in each group. At the beginning of PD therapy the older patients showed higher total fat mass (TFM) expressed as % of total body mass (TBM), lower lean body mass (LBM), lower serum levels of iron, phosphorus and creatinine as well as lower transferrin saturation. When mean values representing the entire PD course were compared, the older patients showed higher TFM as % of TBM and serum ferritin level, whereas lower values were observed for diastolic blood pressure (DBP), LBM, serum creatinine, phosphorus and iron. At the end of PD therapy TFM as % of TBM and serum ferritin level remained higher in older patients as well as lower both DBP and LBM were maintained. Additionally, serum cholesterol level and residual renal function (RRF) became at the end of PD treatment higher in the older individuals compared to the younger ones. The difference in RRF between the two groups was caused by the decline in RRF in the younger patients with relatively stable values of RRF in the older ones. Nutritional parameters improved in the course of PD only in the younger group. In conclusion, the older patients reach similar PD outcome parameters compared to the younger ones while they show higher TFM as % of TBM, stable RRF and more satisfactory DBP. However, elderly patients show a greater progress in the deterioration of indices of both inflammation and atherosclerosis and therefore are not able to improve nutritional parameters.
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PMID:Possible factors contributing to similar peritoneal dialysis outcome in patients over 60 years of age and the younger ones. 1457 6

We have investigated heme oxygenase (HO) and antioxidant status in the novel isolation and characterization of aortic endothelial cells (AECs) from a random bred wild-type strain (WILD) and selectively bred atherosclerosis-susceptible (SUS) and -resistant (RES) strains of Japanese quail. Cultured AECs expressed acetylated LDL, and were probed with endothelial and smooth muscle cell specific antibodies to confirm purity of culture. Subconfluent monolayers of RES AECs had higher HO activity than SUS AECs. At confluence, HO activity levels were similar among strains. However, RES AECs had higher HO-1 protein than WILD and SUS cells. Although ferritin protein levels were similar among the three strains, catalytic iron was higher in SUS AECs than WILD and RES cells. Glutathione levels were highest in SUS cells, intermediate in WILD, and lowest in RES, while glutathione reductase was higher in WILD and RES AECs than SUS AECs. We suggest that differences in atherosclerosis susceptibility between RES and SUS may be due, at least in part, to differences in endothelial HO and antioxidant components.
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PMID:Heme oxygenase and antioxidant status in cultured aortic endothelial cells isolated from atherosclerosis-susceptible and -resistant Japanese quail. 1457

Recent studies on cultured aortic endothelial cells (AECs) from atherosclerosis-susceptible (SUS) and -resistant (RES) strains of Japanese quail suggest that differences in atherosclerosis susceptibility between RES and SUS may be due to differences in endothelial heme oxygenase (HO) and antioxidant components. We have now investigated the effects of oxidant-induced injury on HO and glutathione (GSH) in AECs from SUS and RES quail. We report that cultured AECs from SUS and RES birds differ in their response to oxidative stress. AECs from the SUS strain cells are more susceptible than those from the RES strain to oxidative stress induced by tert-butylhydroperoxide, as judged by lower HO activity, HO-1 expression, ferritin and GSH levels. Aortic endothelial cells from SUS birds also showed higher levels of catalytic iron, TBARS production and LDH release compared with RES cells, indicating that SUS AECs are more susceptible to oxidative stress than cells from the resistant strain. Furthermore, independently of genetic status, AECs from old birds have higher TBARS and lower levels of HSP70 induction than AECs from younger birds, suggesting that aging is associated with a decreased ability of AECs to respond to oxidative stress, and this may be relevant to the permissive effect of aging on the process of atherogenesis. Our results indicate that genetic factors and endogenous antioxidant systems in the blood vessel wall may be important in determining the susceptibility of vascular cells to oxidative stress and atherosclerotic plaque formation.
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PMID:Effects of oxidant-induced injury on heme oxygenase and glutathione in cultured aortic endothelial cells from atherosclerosis-susceptible and -resistant Japanese quail. 1467 83

Nitric acid esters such as glyceryl trinitrate were introduced into therapy more than a century ago and are still widely used for the treatment of myocardial ischemia and its main symptom angina pectoris. The basic mechanisms responsible for the vasodilatory and anti-ischemic action of organic nitrates involve bioactivation of, and nitric oxide (NO) release from, these compounds which have therefore been termed NO donors. The organic nitrate pentaerythritol tetranitrate (PETN) is known to possess antioxidant properties that are thought to be the underlying cause for its specific pharmacological profile. In contrast to other long-acting nitrates, PETN induces tolerance- free vasodilation in humans and was reported to prevent endothelial dysfunction as well as atherogenesis in cholesterol- fed rabbits. However, the exact nature of the vasoprotective signaling pathways triggered by PETN has remained obscure. The present study demonstrates that the active PETN metabolite PETriN stimulates protein expression of the antioxidant defense protein heme oxygenase-1 (HO-1; Figures 1 and 2). Additionally, PETriN enhanced the enzymatic activity of HO-1 measured as formation of the HO-1 metabolites bilirubin (Figure 3) and carbon monoxide (Figure 4) in lysates from endothelial cells. HO-1 induction subsequently led to a marked increase in protein expression of a second antioxidant protein, ferritin, via the HO-1-dependent release of free iron from endogenous heme sources (Figures 1 and 5). Pretreatment of endothelial cells with PETriN was followed by increased cellular resistance to oxidant injury mediated by hydrogen peroxide (Figure 6). Endothelial protection by PETriN was mimicked by exogenous bilirubin which led to an almost complete reversal of hydrogen peroxide-induced toxicity (Figure 8). Increased HO-1 and ferritin expression as well as endothelial protection occurred at micromolar concentrations of PETriN which are well within the range of plasma or tissue levels that can be expected during oral therapy. The capacity to protect the endothelium in vitro may translate into and explain the previously observed antiatherogenic actions of PETN in vivo. In this study, another long-acting nitrate, isosorbide dinitrate (ISDN), did not protect endothelial cells from oxidant damage (Figure 6). The absence of significant cytoprotection in the presence of ISDN was paralleled by a lack of HO-1 and ferritin stimulatory capacity (Figures 2 and 5). ISDN had no significant effect on carbon monoxide release or bilirubin formation (Figures 3 and 4). These observations are in agreement with results demonstrating small or nondetectable amounts of NO released from ISDN and its active metabolite isosorbide mononitrate (ISMN) measured as cyclic GMP formation in RFL-6 reporter cells (Figure 7). Interestingly and in contrast to PETN, isosorbide nitrates are known to induce tolerance to their cardiovascular effects, presumably via oxidant stress. Moreover, in earlier investigations aimed at assessing the antiatherogenic potential of nitrates, PETN but not isosorbide nitrates prevented plaque formation and endothelial dysfunction in animal models of atherosclerosis. Thus, the ability to activate HO-1 induction and associated antioxidant pathways apparently distinguishes PETN from other long-acting nitrates and may explain their different patterns of action in vivo (Figure 9).
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PMID:[Therapy with NO donors-antiatherogenic and antioxidant actions]. 1496 47

The potential effect of iron depletion by blood donation and its relevance to cardiovascular diseases are still under debate. Markers of vascular integrity are increasingly applied in investigations of atherothrombotic diseases. In this study, we investigated whether a lower iron status through blood donation was associated with markers of vascular integrity (circulating oxidised LDL, sICAM-1, sVCAM-1 and vWF-antigen) by comparing healthy male voluntary donors to non-donors, taking into account differences in baseline characteristics. Two fasting blood samples were collected within 1 week from 41 donors and 39 non-donors. The iron status was estimated by measuring the concentration of plasma iron, ferritin, haemoglobin and hematocrit. The markers of iron status were all significantly lower in donors compared to non-donors, especially for ferritin concentrations. However, the lower iron status by blood donation was not reflected in the concentrations of OxLDL, sICAM-1, sVCAM-1 and vWF-antigen in men after adjustment for BMI and ratio total/HDL cholesterol. In order to avoid possible selection-bias related to donorship, we have additionally investigated the difference in marker concentrations within the non-donors, comparing low- and high-ferritin concentrations. This analysis suggests that ferritin concentration is not associated with in vivo LDL oxidation.
Atherosclerosis 2004 Feb
PMID:Is blood donation induced low iron status associated with favourable levels of OxLDL, s-ICAM-1, sVCAM-1 and vWF-antigen in healthy men. 1526 96

Heme oxygenase (HO) degrades heme to carbon monoxide (CO), ferrous ions, and the bile pigment biliverdin, which is subsequently reduced to the other important bile pigment, bilirubin, by biliverdin reductase. Fe2+ liberated from the heme molecule upregulates ferritin production, and bile pigments are potent endogenous antioxidants. The HO enzyme exists in three isophorms: HO-1 is expressed at low levels under physiological conditions, but is induced by numerous factors, including oxidative stress, inflammation, nitric oxide, an elevated level of substrate, and hypoxia. HO-2 is a constitutive enzyme involved in the baseline production of CO in the cardiovascular and nervous systems, whereas HO-3 is also ubiquitously expressed, but possesses low catalytic activity. Like nitric oxide, CO activates soluble guanylate cyclase and elevates cGMP in target tissues, which dilates blood vessels. It also does this by directly activating potassium channels in vascular smooth muscle cells. In addition, CO inhibits platelet aggregation and proliferation of vascular smooth muscle cells, inhibits apoptosis, and stimulates angiogenesis. Both deficiency, and excess of HO-1 may be involved in the pathogenesis of arterial hypertension. Induction of HO-1 attenuates atherosclerosis and myocardial ischemia-reperfusion injury. Pharmacological and genetic induction of HO-1 as well as the delivery of exogenous CO are promising therapeutic strategies for the treatment of cardiovascular diseases.
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PMID:[Heme oxygenase and carbon monoxide in the physiology and pathology of the cardiovascular system]. 1506 78

We investigated whether there is an association between serum ferritin or soluble transferrin receptor (sTfR) concentrations and coronary artery disease (CAD) or its clinical presentations. This is a case-control study that included 892 patients (664 cases with angiographically proven CAD and 228 controls without CAD). Blood was collected before angiography for determination of sTfR, ferritin and C-reactive protein (CRP). The values (median, 25th-75th percentiles) of sTfR (2.6 [2.1; 3.2]mg/l versus 2.4 [2.1; 3.0]mg/l, P = 0.13) or ferritin (140.1 [74.8; 248.3]ng/ml versus 120.1 [74.9; 218.0]ng/ml, P = 0.11) did not differ significantly between cases or controls. The values of sTfR in the case subjects with 1-vessel, 2-vessel, and 3-vessel CAD were: 2.4 [2.0; 3.0], 2.6 [2.0; 3.2], and 2.8 [2.2; 3.3]mg/l, respectively (P = 0.003). In multivariate analysis, neither sTfR (chi2 = 0.14, P = 0.70) nor ferritin (chi2 = 2.8, P = 0.09) correlated independently with the presence of CAD. In case subjects with stable angina, unstable angina, and acute myocardial infarction (MI), ferritin concentrations were: 127.5 [69.5; 214.0], 138.9 [86.1; 278.0], and 175.0 [93.5; 314.5]ng/ml, respectively (P < 0.001). Our results showed that serum concentrations of sTfR or ferritin do not predict the risk for coronary artery disease. In subjects with pre-existing CAD, those with more severe disease had increased levels of sTfR. Patients with CAD presenting with acute coronary syndromes showed increased levels of serum ferritin.
Atherosclerosis 2004 May
PMID:Value of serum ferritin and soluble transferrin receptor for prediction of coronary artery disease and its clinical presentations. 1513 58


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