Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The consumption of a cholesterol-enriched diet increases the degree of lipid peroxidation, which is one of the early processes of atherosclerosis. The aim of this trial was to determine the antioxidative effects of the citrus bioflavonoid, naringin, a potent cholesterol-lowering agent, compared to the cholesterol-lowering drug, lovastatin, in rabbits fed a high cholesterol diet. Male rabbits were served a high-cholesterol (0.5%, w/w) diet or high-cholesterol diet supplemented with either naringin (0.5% cholesterol, 0.05% naringin, w/w) or lovastatin (0.5% cholesterol, 0.03% lovastatin, w/w) for 8 weeks to determine the plasma and hepatic lipid peroxide, plasma vitamin A and E levels, and hepatic hydrogen peroxide levels, along with the hepatic antioxidant enzyme activities and gene expressions. Only the lovastatin group showed significantly lower plasma and hepatic lipid peroxide levels compared to the control group. The naringin supplementation significantly increased the activities of both hepatic SOD and catalase by 33% and 20%, respectively, whereas the lovastatin supplementation only increased the catalase activity by 23% compared to control group. There was no difference in the GSH-Px activities between the various groups. Content of H2O2 in hepatic mitochondria was significantly lower in groups supplemented with lovastatin and naringin than in control group. However, there was no difference in cytosolic H2O2 content in liver between groups. The concentration of plasma vitamin E was significantly increased by the naringin supplementation. When comparing the antioxidant enzyme gene expression, the mRNA expression of SOD, catalase and GSH-Px was significantly up-regulated in the naringin-supplemented group. Accordingly, these results would appear to indicate that naringin, a citrus bioflavonoid, plays an important role in regulating antioxidative capacities by increasing the SOD and catalase activities, up-regulating the gene expressions of SOD, catalase, and GSH-Px, and protecting the plasma vitamin E. In contrast, lovastatin exhibited an inhibitory effect on the plasma and hepatic lipid peroxidation and increased the hepatic catalase activity in high-cholesterol fed rabbits.
 ...
PMID:Antioxidative activity of naringin and lovastatin in high cholesterol-fed rabbits. 1172 89

High plasma homocysteine concentrations have been found to be associated with atherosclerosis and thrombosis of arteries and deep veins. The oxidative damage mediated by hydrogen peroxide production during the metal-catalyzed oxidation of homocysteine is to date considered to be one of the major pathophysiological mechanisms for this association. In this work, a very sensitive and accurate method was employed to measure the effective production of H2O2 during homocysteine oxidation. Furthermore, the interaction of homocysteine with powerful oxidizing species (hypochlorite, peroxynitrite, ferrylmyoglobin) was evaluated in order to ascertain the putative pro-oxidant role of homocysteine. Our findings indicate that homocysteine does not produce H2O2 in a significant amount (1/4000 mole/mole ratio of H2O2 to homocysteine). Moreover, homocysteine strongly inhibits the oxidation of luminol and dihydrorhodamine by hypochlorite or peroxynitrite and rapidly reduces back ferrylmyoglobin, the oxidizing species, to metmyoglobin. All these results should, in our opinion, lead to a rethinking of the commonly held view that homocysteine oxidation is one of the main causative mechanisms of cardiovascular damage.
 ...
PMID:Is homocysteine a pro-oxidant? 1176 8

Endothelin-1 (ET-1) and oxidized low-density lipoprotein (ox-LDL) are associated with atherosclerosis and essential hypertension. We assessed the effect of mildly oxidized LDL (mox-LDL) and ox-LDL and their major oxidative components, i.e., reactive oxygen species (ROS), lysophosphatidylcholine (LPC), and 4-hydroxy-2-nonenal (HNE) and their interaction with ET-1 on vascular smooth muscle cell (VSMC) proliferation. Growth-arrested VSMCs isolated from the rabbit aorta were incubated with different concentrations of LDL, mox-LDL, ox-LDL, hydrogen peroxide (H(2)O(2)) (a donor of ROS), LPC, or HNE with or without ET-1. DNA synthesis in VSMCs was measured by [(3)H] thymidine incorporation. Mox-LDL, ox-LDL, H(2)O(2), LPC, HNE, or ET-1 stimulated DNA synthesis in a dose-dependent manner. Maximal effect was observed at 5 microg/ml for mox-LDL (162%) or ox-LDL (154%), 15 microM LPC (156%), 5 microM H2O2 (177%), 1 microM HNE (144%), and 0.1 microM ET-1 (195%). By contrast, LDL was without any significant effect. When added together, there was no synergistic effect of LDL, H2O2, or HNE with ET-1 on DNA synthesis. However, the effect of mox-LDL (0.1 microg/ml), ox-LDL (0.5 microg/ml), or LPC (10 microM) was potentiated by ET-1 (114%-338%, 133%-425%, 118%-333%, respectively). The mitogenic effect of mox-LDL, ox-LDL, or LPC and their interaction with ET-1 were inhibited by defatted albumin (10 microg/ml), antioxidant N-acetylcysteine (400 microM), the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium (1 microM). The ET(A/B) receptor antagonist TAK044 (1 microM) or the MAPK kinase inhibitor PD098059 (10 microM) inhibited the mitogenic effect of ET-1 and its interaction with mox-LDL, ox-LDL, or LPC. The synergistic interaction of mox-LDL, ox-LDL, or LPC with ET-1 was completely reversed by the combined use of N-acetylcysteine and TAK044. Our results suggest that mox-LDL, ox-LDL, and their major phospholipid component LPC act synergistically with ET-1 in inducing VSMC proliferation by way of the activation of redox-sensitive and MAPK pathways.
 ...
PMID:Lysophosphatidylcholine is a major contributor to the synergistic effect of mildly oxidized low-density lipoprotein with endothelin-1 on vascular smooth muscle cell proliferation. 1186 25

Human studies suggest a beneficial effect of eicosapentaenoic acid (EPA)-supplemented diets on atherosclerotic and atherothrombotic disorders as well as autoimmune and inflammatory diseases and tumors. The effects of EPA on human monocyte survival and maturation into macrophage are not yet known. We studied the effects of EPA on the survival and development into macrophage of human monocyte treated with colony-stimulating factor (CSF). We have found that EPA induces cell death of the monocyte via apoptosis, even in the presence of M-CSF or GM-CSF, and inhibits differentiation from the monocyte to macrophage by inducing H2O2 production. In contrast to the effect of EPA on monocytes, EPA did not induce cell death of monocyte-derived macrophages. Such an apoptosis inducing effect on monocytes by EPA may contribute to the efficacy of EPA in atherosclerosis and autoimmune diseases.
 ...
PMID:Eicosapentaenoic acid inhibits CSF-induced human monocyte survival and maturation into macrophage through the stimulation of H2O2 production. 1205 Jan 83

To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we established an in vitro transfection of human HO-1 gene into rat VSMC mediated by a retroviral vector. The results showed that the profound expression of HO-1 protein as well as HO activity was 1.8- and 2.0-fold increased respectively in the transfected cells compared to the non-transfected ones. The treatment of VSMC with different concentrations of H2O2 led to the remarkable cell damage as indicated by survival rate and LDH leakage. However, the resistance of the HO-1 transfected VSMC against H2O2 was significantly raised. This protective effect was dramatically diminished when the transfected VSMC were pretreated with ZnPP-IX, a specific inhibitor of HO, for 24 h. In addition, we found that the growth potential of the transfected cells was significantly inhibited directly by increased activity of HO-1, and this effect might be related to decreased phosphorylation of MAPK. These results suggest that the overexpression of introduced hHO-1 is potentially able to reduce the risk factors of atherosclerosis, partially due to its cellular protection against oxidative injury and to its inhibitory effect on cellular proliferation.
 ...
PMID:Overexpression of heme oxygenase-1 protects smooth muscle cells against oxidative injury and inhibits cell proliferation. 1211 38

Oxidative damage in the vascular system has been linked to the development of atherosclerosis. The aim of the present study was to establish a cell culture model for the investigation of in vitro induced oxidative DNA injury, its modulation and repair kinetics. Primary cultures of human coronary artery smooth muscle cells were used as target cells. The cells were exposed to hydrogen peroxide (H2O2). DNA damage was quantified by the alkaline single-cell gel electrophoresis assay (comet assay). This method allows quantification of DNA single and double strand breaks and of alkali-labile sites in individual cells. In the present study H2O2 concentration-responses and dependence of damage on exposure time and temperature were evaluated and the repair kinetics were studied. The results show that this cell culture model can be employed to study oxidative DNA injury in the cells of the human cardiovascular system, a promoter of cardiovascular disease. Further it offers the possibility to investigate pharmacological modulators of such oxidative effects. Such modulators are antioxidants like vitamin C and E, steroid hormones, phytoestrogens, or synthetic agents. Today, pigs, rabbits or rats are used to test systemic and local administration of the named modulating substances, the latter by use of special catheters or stents placed inside the arteries. These experiments require treatment observation over a number of weeks and killing of the animals at the end of the experiment. By using the proposed cell culture model such animal experiments could be partly avoided.
 ...
PMID:Development of an in vitro model to study oxidative DNA damage in human coronary smooth muscle cells. 1216 14

Resveratrol (3,4',5-trihydroxystilbene) is a natural phytoalexin synthesized in response to injury or fungal attack, found in the grape skin and wine, specially red wine. A large number of studies have demonstrated that resveratrol regulates many biological activities, namely protection against atherosclerosis by a set of pharmacological properties, including the antioxidant activity. In this study, we explored the capacity of resveratrol in protecting low density lipoproteins (LDL) against either ferrylmyoglobin- or peroxynitrite-mediated oxidation and the underlying mechanisms of its antioxidant potential. Resveratrol efficiently decreases the accumulation of hydroperoxides in LDL promoted by ferrylmyoglobin, a potent oxidant formed by the reaction of metmyoglobin with hydrogen peroxide, in a concentration-dependent manner, promptly reducing the oxoferryl complex to metmyoglobin. Simultaneously, resveratrol is consumed as detected by the rapid decrease in the characteristic peak at 310 nm, in a similar way to that observed upon its reaction with peroxidase/H2O2, pointing to a mechanism of one-electron oxidation and subsequent resveratrol dimer formation. On the other hand, resveratrol inhibits LDL apoprotein modifications induced by peroxynitrite, another potent oxidant formed by the reaction between superoxide and nitric oxide, as assessed by the decrease in apo-B net charge alterations and in carbonyl groups formation mediated by that oxidant. Resveratrol also interacts with peroxynitrite in a similar way to that observed with laccases, suggesting a mechanism of resveratrol oxidation rather than a nitration one. These mechanisms are discussed. Considering that either ferrylmyoglobin or peroxynitrite are physiologically relevant oxidants implicated in several pathologies, including atherosclerosis, our results certainly contribute to the understanding of the antioxidant action of resveratrol and consequently provide a new approach for the cardiovascular benefits associated with moderate consumption of red wine.
 ...
PMID:The interaction of resveratrol with ferrylmyoglobin and peroxynitrite; protection against LDL oxidation. 1218 Jan 87

We examined the mechanism of action of lysophosphatidylcholine (lyso-PC), which is suggested to be involved in the pathogenesis of atherosclerosis and inflamatory disorders, and its interaction with well-known vasoactive compounds such as hydrogen peroxide (H2O2), thromboxane A2 (TX-A2), serotonin (5-HT), angiotensin II (Ang-II), endothelin-1 (ET-1), or urotensin II (U-II) on VSMC proliferation. Growth-arrested rabbit VSMCs were incubated with given concentrations of lyso-PC with H202, TX-A2, 5-HT, Ang-II, ET-1, or U-II. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. Lyso-PC induced a maximal effect on [3H]thymidine incorporation at a concentration of 15 microM (156%), and its effect was significantly inhibited by the phospholipase C inhibitor U73122 (10 microM), the intracellular antioxidant NAC (400 microM), and the NADPH oxidase inhibitor diphenylene iodonium (1 microM), but not by the MAPK kinase inhibitor (10 microM). H2O2, TX-A2, 5-HT, Ang-II, ET-1, or U-II also stimulated [3H]thymidine incorporation in a dose-dependent manner. A non-mitogenic concentration of lyso-PC (5 microM) significantly potentiated the effect of low concentrations of H2O2 (0.1 microM, 110 to 222%), TX-A2 (5 microM, 120 to 202%), 5-HT (5 microM, 182 to 259%), Ang-II (0.5 microM, 167 to 304%), ET-1 (0.01 microM, 139 to 297%), or U-II (0.025 microM, 120 to 332%) on [3H]thymidine incorporation. The results suggest that lyso-PC acts synergistically with the vasoactive compounds H2O2, TX-A2, 5-HT, Ang-II, ET-1, or U-II in inducing VSMC proliferation, which may play an important role in the progression of atherosclerosis.
 ...
PMID:Lysophosphatidylcholine potentiates the mitogenic effect of various vasoactive compounds on rabbit aortic smooth muscle cells. 1222 16

The aim of this study was to investigate intracellular levels of reactive oxygen species (ROS) in circulating leukocytes in populations at risk for atherosclerosis compared with in healthy individuals. The study populations consisted of 27 non-diabetic men (aged 40-69 years) with untreated hypercholesterolemia (HC), 13 individuals (aged 39-56 years) with well-controlled insulin-dependent diabetes mellitus (DM), and 20 healthy individuals (aged 26-61 years) (REF). Citrated whole blood was collected in fasting condition. Using flow cytometric techniques, the resting levels and the response upon phorbol 12-myristate 13-acetate (PMA, 100 ng/mL) stimulation of ROS were measured in circulating monocytes (MO) and granulocytes (GR). The relative mean fluorescence intensity (rMFI) in 10(4) leukocytes of fluorochromes mainly reflecting the levels of peroxynitrite (ONOO-) hydrogen peroxide (H2O2) and superoxide anion (O2-) was recorded. Significantly, higher basal levels of ONOO- in GR from the combined risk population compared with REF were found (1.4 vs. 1.5 rMFI, p<0.05). Upon PMA stimulation, significantly lower levels of O2 in GR in the risk populations compared to REF (119 vs. 90 Si, p<0.001) were observed. In conclusion, increased resting levels of ROS in circulating granulocytes, but reduced response to PMA stimulation could be demonstrated in populations at risk for atherosclerosis compared with in healthy individuals. This might indicate a higher degree of resting oxidative reactions, with partly exhausted cells and less capacity to host defence.
 ...
PMID:Reactive oxygen species generation by leukocytes in populations at risk for atherosclerotic disease. 1246 98

Oxidative stress has been implicated in the pathogenesis of a host of vascular abnormalities such as atherosclerosis, hypertension and in restenosis followed by balloon angioplasty. However, the molecular mechanism by which oxidative stress causes these abnormalities remains poorly characterized. Recent studies have shown that exposure of vascular smooth muscle cells (VSMC) with H2O2, to mimic oxidative stress, activates components of growth promoting and proliferative signal transduction pathways. These components include mitogen-activated protein kinases (MAPKs) and protein kinase B (PKB/Akt), and are believed to be key players mediating growth, proliferation, hypertrophy, migration, survival and death of VSMC. We provide a brief overview of the effect of H2O2 on MAPKs and PKB/Akt signaling in VSMC in relation to their potential role in the pathogenesis of vascular diseases.
 ...
PMID:Synchronous activation of ERK 1/2, p38mapk and PKB/Akt signaling by H2O2 in vascular smooth muscle cells: potential involvement in vascular disease (review). 1252 83


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>