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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukocyte adhesion to endothelial cells plays a key role in inflammatory processes associated with end-organ injury. Endothelin-1 (ET-1), which stimulates inflammatory processes, contributes to cardiovascular damage in deoxycorticosterone (DOCA)-salt hypertension. We investigated whether ETA receptor blockade modulates in vivo leukocyte-endothelial cell interactions and expression of cell adhesion molecules (CAM) involved in these processes. DOCA-salt and control uninephrectomized rats were treated with the ETA antagonist BMS182874 (40 mg/kg per day) or vehicle. Analysis of CAMs expression by reverse transcription-polymerase chain reaction and immunohistochemistry showed increased cardiac platelet selectin (P-selectin), detected mainly in endothelial cells, and vascular cell adhesion molecule-1 (VCAM-1), but not intercellular adhesion molecule-1 (ICAM-1), in DOCA-salt rats. Cardiac expression of endothelial selectin (E-selectin) was decreased, whereas immunoreactivity to ED-1 and myeloperoxidase (MPO) activity, markers of macrophage and leukocyte infiltration, respectively, were increased in DOCA-salt. Leukocyte-endothelial cell interaction, functionally assessed in venules of internal spermatic fascia by intravital microscopy, was significantly altered in DOCA-salt rats as evidenced by increased leukocyte adhesion and decreased rolling. BMS182874 treatment normalized leukocyte-endothelium interactions, decreased cardiac VCAM-1 expression in DOCA and control groups, and had no effects on ICAM-1 expression. BMS182874 also increased E-selectin and abolished P-selectin expression in DOCA-salt, but not in control rats. The ETA antagonist reduced cardiac ED-1 content and MPO activity and prevented cardiac damage in DOCA-salt rats. These data indicate that ET-1 participates, via activation of ETA receptors, in altered leukocyte-endothelial cell interactions in DOCA-salt rats, possibly by modulating expression of CAMs, and that the inflammatory status is associated with cardiac damage in mineralocorticoid hypertension.
Hypertension 2004 Apr
PMID:ETA receptor mediates altered leukocyte-endothelial cell interaction and adhesion molecules expression in DOCA-salt rats. 1499 93

A 73-year-old man was admitted to the hospital because of progressive lethargy and fever. He had a history of hypertension since the age of 40, and was diagnosed as having a testicular tumor at the age of 50. On admission, he looked pale and stuporous. Laboratory examination revealed microscopic hematuria. The erythrocyte sedimentation rate was 110 mm/hr, and the serum CRP was 14.3 mg/dl. The titer of myeloperoxidase-antineutrophilic cytoplasmic antibodies (MPO-ANCA) was higher than 1:1000. On the sixth hospital day, he required ventilatory assistance because of aspiration pneumonia and was connected to a respirator. He was treated with intravenous corticosteroids, to which he responded in the short term with resolution of the fever and decrease in the serum CRP level, however, the consciousness disturbance persisted and the fever recurred soon thereafter. He developed gross hematuria and the renal function deteriorated. He eventually died of renal failure and pulmonary hemorrhage. Although his clinical course and laboratory findings were consistent with those of microscopic polyangitis, the pathological diagnosis was crescentic glomerulonephritis with no evidence of vasculitis.
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PMID:A 73-year-old man with confusion, fever, and positive MPO-ANCA. 1524 15

Pathological conditions that predispose to cardiovascular events, such as hypertension, hypercholesterolemia, and diabetes, are associated with oxidative stress. These observations and further data derived from a plethora of investigations provided accumulating evidence that oxidative stress is decisively involved in the pathogenesis of endothelial dysfunction and atherosclerosis. Several enzymes expressed in vascular tissue contribute to production and efficient degradation of reactive oxygen species, and enhanced activity of oxidant enzymes and/or reduced activity of antioxidant enzymes may cause oxidative stress. Various agonists, pathological conditions, and therapeutic interventions lead to modulated expression and function of oxidant and antioxidant enzymes, including NAD(P)H oxidase, endothelial nitric oxide synthase, xanthine oxidase, myeloperoxidase, superoxide dismutases, catalase, thioredoxin reductase, and glutathione peroxidase. Data from numerous studies underline the importance of dysregulated oxidant and antioxidant enzymes for the development and progression of atherosclerotic disease in animal models and humans. Specific pharmacological modulation of key enzymes involved in the propagation of oxidative stress rather than using direct antioxidants may be an approach to reduce oxygen radical load in the vasculature and subsequent disease progression in humans. This review focuses on the modulation of expression and activity of major antioxidant and oxidant enzymes expressed in vascular cells.
Hypertension 2004 Oct
PMID:Modulation of oxidant and antioxidant enzyme expression and function in vascular cells. 1533 34

The main problem nephrologists have to face today is the very high patient morbidity and mortality. A number of traditional and non-traditional risk factors have a role; among these anaemia, hypertension, dislipidemia, abnormalities in calcium-phosphate metabolism, hyperhomocysteinemia and endothelial dysfunction. An important innovation in the field of hemodialysis has been the availability of high-permeable and high-flux membranes, characterized by a high biocompatibility and ultrafiltration coefficient. The development of automatic systems to control ultrafiltration has enabled the utilisation of these membranes in the clinical setting (high-flux hemodialysis, hemofiltration, hemodiafiltration). It is common opinion that high-flux membranes can positively influence cardiovascular instability, but this has not been confirmed by clinical trials. Although preliminary data indicated a favorable effect on the correction of anemia in patients treated with high-permeable membranes, randomized trials have not shown a significant effect. Better control of anemia could be possible by means of on-line treatments, given their higher removal of medium- and large molecules and reduced microbiological and pyrogenic contamination of the dialysate. A number of analyses showed a lower incidence of bone cysts and/or carpal tunnel syndrome in patients treated with high-flux membranes compared to low-flux ones. High-flux treatments could reduce morbidity and mortality in hemodialysis patients. However, despite its large sample size, the HEMO Study has not been capable of showing a statistically significant effect of higher dialysis dose and high-flux membranes on survival and morbidity. The MPO study has been expressively designed to do a prospective evaluation of the long-term effect of membrane permeability on clinical outcomes. These results are greatly awaited.
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PMID:[Clinical dialysis: new problems and new prospects]. 1535 50

Aldehydes are organic compounds that are widespread in nature. They can be formed endogenously by lipid peroxidation (LPO), carbohydrate or metabolism ascorbate autoxidation, amine oxidases, cytochrome P-450s, or myeloperoxidase-catalyzed metabolic activation. This review compares the reactivity of many aldehydes towards biomolecules particularly macromolecules. Furthermore, it includes not only aldehydes of environmental or occupational concerns but also dietary aldehydes and aldehydes formed endogenously by intermediary metabolism. Drugs that are aldehydes or form reactive aldehyde metabolites that cause side-effect toxicity are also included. The effects of these aldehydes on biological function, their contribution to human diseases, and the role of nucleic acid and protein carbonylation/oxidation in mutagenicity and cytotoxicity mechanisms, respectively, as well as carbonyl signal transduction and gene expression, are reviewed. Aldehyde metabolic activation and detoxication by metabolizing enzymes are also reviewed, as well as the toxicological and anticancer therapeutic effects of metabolizing enzyme inhibitors. The human health risks from clinical and animal research studies are reviewed, including aldehydes as haptens in allergenic hypersensitivity diseases, respiratory allergies, and idiosyncratic drug toxicity; the potential carcinogenic risks of the carbonyl body burden; and the toxic effects of aldehydes in liver disease, embryo toxicity/teratogenicity, diabetes/hypertension, sclerosing peritonitis, cerebral ischemia/neurodegenerative diseases, and other aging-associated diseases.
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PMID:Aldehyde sources, metabolism, molecular toxicity mechanisms, and possible effects on human health. 1641 45

Oxidative stress plays a critical role in the pathogenesis of cardiovascular disease and diabetes. Studies in vascular cells and experimental animals have demonstrated that the angiotensin type-1 receptor (AT1R) contributes to formation of reactive oxygen species by activating nicotinamide-adenine dinucleotide phosphate oxidases, but the relevance of this pathway to human heart disease has not been established. Here we demonstrate that a polymorphism in the AT1R gene (A1166C), linked to increased receptor activity, is associated with elevated levels of oxidative stress markers in heart failure patients but not in healthy controls. Plasma protein carbonyls (PCs), a marker of oxidative protein modification, were 10-fold higher in heart-failure patients compared with controls [geometric means and 95% CIs for patients, 75 (57 to 100) pmol/mg; controls, 5 (4 to 7) pmol/mg; P<0.001]. Moreover, levels of PCs were 50-fold higher in patients homozygous for the polymorphism (CC) than in controls and significantly higher than the AA and AC genotype patient groups [CC: 273 (135-550); AC: 59 (35-98); AA: 65 (40-106) pmol/mg; P<0.001]. Levels of myeloperoxidase were also modestly increased in heart-failure patients [51 (46-57) ng/mL] compared with controls [37 (32-44) ng/mL; P<0.001], but were especially elevated in patients with a CC genotype [CC: 72 (58-89); AC: 52 (44-61); AA: 39 (34-46) ng/mL; P<0.001]. The AT1R genotype was demonstrated to be an independent predictor of both PCs and myeloperoxidase levels in heart-failure patients. These findings suggest that oxidative stress in human heart failure is regulated via angiotensin signaling and may involve the nicotinamide dinucleotide oxidase pathway.
Hypertension 2006 Jun
PMID:Angiotensin type-1 receptor A1166C gene polymorphism correlates with oxidative stress levels in human heart failure. 1665 60

Reactive oxygen species (ROS) contribute to the pathogenesis of cardiovascular diseases including hypertension, atherosclerosis, cardiac hypertrophy, heart failure and diabetes mellitus. Oxidative stress is resulted from excessive generation of ROS that outstrips the antioxidant system. Various agonists, pathological conditions and therapeutic interventions lead to modulated expression and function of oxidant and antioxidant enzymes, including NAD(P)H oxidase, endothelial nitric oxide synthase, xanthine oxidase, myeloperoxidase, superoxide dismutases, catalase and glutathione peroxidase. ROS formed in vascular wall target a wide range of signaling molecules and cellular pathways in both endothelium and vascular smooth muscle, such as transcription factors, protein tyrosine phosphatase, protein tyrosine kinase, mitogen-activated protein kinase, Ca(2+)-transporting system and protein modification. ROS also have distinct physiological and pathophysiological impacts on vascular cells. ROS contribute to vascular dysfunction and remodeling through oxidative damage by (1) reducing the bioavailability of NO, (2) impairing endothelium-dependent vasodilatation and endothelial cell growth, (3) causing apoptosis or anoikis, (4) stimulating endothelial cell migration, and (5) activating adhesion molecules and inflammatory reaction, leading to endothelial dysfunction, an initial episode progressing toward hypertension and atherosclerosis. Cellular events underlying these processes involve changes in vascular smooth muscle cell growth, apoptosis/anoikis, cell migration, inflammation, and vasoconstriction. The present communication focuses on the biology of ROS signaling in vascular cells, discusses how oxidative stress contributes to vascular damage, and the therapeutic strategies/biotic factors that can prevent or treat ROS-associated cardiovascular disorders.
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PMID:Reactive oxygen species in vascular wall. 1672 32

Acute right ventricular (RV) failure following pulmonary embolism (PE) is a strong predictor of poor clinical outcome. Present studies test for an association between RV failure from experimental PE, inflammation, and upregulated chemokine expression. Additional experiments test if neutrophil influx contributes to RV dysfunction. PE was induced in male rats by infusing 24 microm microspheres (right jugular vein) producing mild hypertension (1.3 million beads/100 g, PE1.3), or moderately severe hypertension (2.0 million beads/100 g, PE2.0). Additional rats served as vehicle sham (0.01% Tween 20, Veh). In vivo RV peak systolic pressures (RVPSP) increased significantly, and then declined following PE2.0 (51 +/- 1 mm Hg 2 h; 49 +/- 1, 6 h; 44 +/- 1, 18 h). RV generated pressure of isolated, perfused hearts was significantly reduced in PE2.0 compared with PE1.3 or Veh. MCP-1 protein (ELISA) was elevated 21-fold and myeloperoxidase activity 95-fold in RV of PE2.0 compared with Veh or PE1.3. CINC-1, CINC-2, MIP-2, MCP-1, and MIP-1alpha mRNA also increased in RV of PE2.0. Histological analysis revealed massive accumulation of neutrophils (selective esterase stain) and monocyte/macrophages (CD68, ED-1) in RV of PE2.0 hearts in regions of myocyte damage. Electron microscopy showed myocyte necrosis and phagocytosis by inflammatory cells. LV function was normal and did not show increased inflammation after PE2.0. Treatment with anti-PMN antibody reduced RV MPO activity and prevented RV dysfunction. Conclusions-PE with moderately severe pulmonary hypertension (PE2.0) resulted in selective RV dysfunction, which was associated with increased chemokine expression, and infiltration of both neutrophils and monocyte/macrophages, indicating that a robust immune response occurred with RV damage following experimental PE. Experimental agranulocytosis reduced RV, suggesting that neutrophil influx contributed to RV damage.
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PMID:Cardiac inflammation contributes to right ventricular dysfunction following experimental pulmonary embolism in rats. 1681 20

Corosolic acid (CRA), a constituent of banaba leaves, has been reported to have anti-inflammatory and hypoglycemic activities. The aim of this study was to determine the effects of CRA on metabolic risk factors including obesity, hypertension, hyperinsulinemia, hyperglycemia, and hyperlipidemia together with oxidative stress and inflammation, all of which are characteristic of the SHR/NDmcr-cp (cp/cp) (SHR-cp) rat, an animal model of metabolic syndrome. Six-week-old male SHR-cp rats were fed a high fat diet containing 0.072% CRA for 14 weeks. Treatment with CRA lowered blood pressure, which was elevated in control animals, by 10% after 8 weeks, and serum free fatty acids by 21% after 2 weeks. CRA treatment resulted in decreases in the levels of the oxidative stress markers thiobarbituric acid-reactive substances and 8-hydroxydeoxyguanosine by 27% and 59%, respectively, after 2 weeks. CRA treatment also reduced the levels of myeloperoxidase markers, 3-nitrotyrosine and 3-chlorotyrosine by 38% and 39%, respectively, after 10 weeks, and tended to decrease the levels of high sensitivity C-reactive protein, a marker of inflammation, after 6 weeks. However, CRA had no effect on weight gain or hyperglycemia. These results demonstrate that CRA can ameliorate hypertension, abnormal lipid metabolism, and oxidative stress as well as the inflammatory state in SHR-cp rats. This implies that CRA can be beneficial for preventing atherosclerosis-related diseases that are an increasing health care problem worldwide.
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PMID:Corosolic acid prevents oxidative stress, inflammation and hypertension in SHR/NDmcr-cp rats, a model of metabolic syndrome. 1695 74

Ischemic heart disease and myocardial infarction in patients with SLE--are usually secondary to early coronary atherosclerosis. Estimation if antiphospholipid syndrome and antiphospholipid antibodies are the risk factor for myocardial infarction and ischemic heart disease in patients with TRU. We examined 129 patients with SLE (114 women and 15 men). All the patients underwent comprehensive physical examination. ECG, ultrasound heart examinations were performed. They were followed by heart scintygraphic examination if indicated. Routine biochemical and hematological laboratory tests were performed including fasting glucose level, concentration of homocysteine, uric acid and lipids. Wide range of immunological essays were performed, testing for antinuclear antibodies (ANA), extractable nuclear antigen antibodies (ENA), antiphospholipid antibodies (anticardiolipin antibodies--aCL, lupus anticoagulant--LA, antiprothrombine antibodies aPT, anti-beta2glicoprotein-I antibodies), anti-dsDNA antibodies, anti-nucleosome antibodies, antihistone antibodies, antineutrophil cytoplasmic antibodies (ANCA) and antiendothelial antibodies (AECA). Statistical analysis was performed with chi2 Yates, chi2 Pearson and R rang Spearman tests. Multivariate regression analysis was also done. Ischemic heart disease was found in 20 (15.5%) SLE patients, myocardial infarctions were diagnosed in 9 (6.97%). Ischemic heart disease and myocardial infarction were significantly related to presence of secondary antiphospholipid syndrome (SAPS), OR: 4.21, p = 0.008 and OR: 12.8; p = 0.02 respectively). They were also related to high activity of SLE, OR: 7.18; p = 0.012 and OR: 27.3; p = 0.006 respectively. Ischemic heart disease was significantly more common in older patients (52.75 years versus 42.15 years; p = 0.0008) and in patients with hypertension (p < 0.05). Impaired glucose tolerance (OR: 8.44; p = 0.03), presence of aCL IgG (OR; 2.93; p = 0.05) and p-ANCA anti-MPO (OR: 6.08; p = 0.036) were found to be risk factors of ischemic heart disease. Myocardial infarction was significantly associated with high uric acid level (OR: 5.01; p = 0.052) and impaired glucose tolerance (OR: 7.42; p = 0.047) and with presence of the following antibodies: aCL IgG and/or aCL IgM (OR: 5.61; p = 0.039), ANCA in the indirect immunofluorescence essay (OR: 5.78; p = 0.035), anti-MPO antibodies (OR: 6.58; p = 0.051) and AECA (OR: 11.10; p = 0.026). Presence of antiphospholipid antibodies and SAPS are significant risk factors of ischemic heart disease and myocardial infarction in SLE patients. The risk factors of ischemic heart disease and myocardial infarction in SLE patients significantly differ from the ones in general population.
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PMID:[Antiphospholipid syndrome and antiphospholipid antibodies as a risk factors of ischaemic heart disease and myocardial infarction in patients with systemic lupus erythematosus]. 1719 52


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