Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the last 10 years, there has been an explosion of interest in homocysteine, a sulfur-containing amino acid that occupies a central location in the metabolic pathways of thiol compounds. This interest is primarily because of the realization that hyperhomocysteinemia is an important risk factor for vascular disease, including stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. Since elevated homocysteine levels can often be normalized by supplementing the diet with folic acid (folate), pyridoxine hydrochloride (vitamin B(6)), and cyanocobalamin (vitamin B(12)), these observations raise the exciting possibility that this inexpensive and well-tolerated therapy may be effective in decreasing the incidence of vascular disease. In addition to its association with cerebrovascular disease, homocysteine may play a role in neurodegenerative disorders, even if only as a marker of functional vitamin B(12) deficiency. Homocysteine is also important to neurologists since most anticonvulsants raise homocysteine levels, an effect that may explain the teratogenic effects of these drugs. Practical knowledge concerning some details of homocysteine metabolism, the diagnosis of hyperhomocysteinemia, and the use of polyvitamin therapy to lower homocysteine levels will be increasingly important in the treatment of patients with neurologic disease. Arch Neurol. 2000;57:1422-1428
 ...
PMID:Homocysteine and neurologic disease. 1103 Jul 93

Various lifestyle factors have been associated with increasing the risk of stroke. These include lack of exercise, alcohol, diet, obesity, smoking, drug use, and stress. Guidelines endorsed by the Centers for Disease Control and Prevention and the National Institutes of Health recommend that Americans should exercise for at least 30 minutes of moderately intense physical activity on most, and preferably all, days of the week. Recent epidemiologic studies have shown a U-shaped curve for alcohol consumption and coronary heart disease mortality, with low-to-moderate alcohol consumption associated with lower overall mortality. High daily dietary intake of fat is associated with obesity and may act as an independent risk factor or may affect other stroke risk factors such as hypertension, diabetes, hyperlipidemia, and cardiac disease. Homocysteine is another important dietary component associated with stroke risk, while other dietary stroke risk factors are thought to be mediated through the daily intake of several vitamins and antioxidants. Smoking, especially current smoking, is a crucial and extremely modifiable independent determinant of stroke. Despite the obstacles to the modification of lifestyle factors, health professionals should be encouraged to continue to identify such factors and help improve our ability to prevent stroke.
 ...
PMID:Lifestyle factors and stroke risk: exercise, alcohol, diet, obesity, smoking, drug use, and stress. 1112 40

Traditional risk factors for coronary artery disease (CAD) can only explain approximately two thirds of the observed clinical events. This has maintained interest in other nutritional and biochemical factors that might contribute to the underlying pathophysiology of vascular disease. Two such factors are dietary antioxidants and plasma homocysteine. Established risk factors such as hypertension, smoking and diabetes mellitus are all associated with increased oxidative stresses due to excess free radical activity in the vascular wall. This may facilitate the development of vascular disease because of (i) increased oxidation of low-density lipoprotein (LDL) particles which increases their propensity to deposition in the vascular wall, (ii) inactivation of endothelium-derived nitric oxide, and (iii) direct cytotoxicity to endothelial cells. Protective antioxidant molecules include vitamin C and vitamin E of which the latter is lipid soluble and is the primary antioxidant defence in circulating LDL particles. Epidemiological studies have suggested strongly that individuals who have high circulating concentrations or dietary intake of natural antioxidant vitamins are protected against vascular disease events (18). Furthermore, many studies have demonstrated a beneficial effect of natural and synthetic antioxidants on surrogate markers of vascular disease such as endothelial function and lipoprotein oxidation. However, large prospective randomized controlled intervention trials, mostly involving vitamin E (e.g. CHAOS, HOPE (22)), have failed to demonstrate any beneficial effect upon vascular mortality in high risk individuals. Possible reasons for these disappointing results include the pro-oxidant effects of high dose antioxidant supplements, particularly in patients with established vascular disease. Homocysteine is a sulphydryl-containing amino acid derived from the demethylation of dietary methionine. Epidemiological studies over 30 years have shown that increased concentrations of homocysteine are associated with vascular disease. This link is independent of other risk factors, is consistent across many studies and is strongly dose-related. Recently, evidence has accumulated to suggest that this link is also biologically plausible because homocysteine promotes oxidant injury to the vascular endothelium, impairs endothelium-dependent vasomotor regulation and may also alter the coagulant properties of the blood. Plasma homocysteine levels can be reduced by dietary supplements of folic acid and B vitamins. Studies are currently being undertaken to examine the impact of these vitamins in high risk patients and, thereby, establish a causative role for homocysteine in promoting vascular events.
 ...
PMID:Coronary artery disease--free radical damage, antioxidant protection and the role of homocysteine. 1119 56

Oxidative stress has been implicated in atherosclerosis and its underlying conditions. LOX-1 is a novel endothelial receptor for oxidized low-density lipoprotein which might mediate endothelial dysfunction and subsequent atherogenesis. In the present study, we examined LOX-1 gene regulation by oxidative stress. First, superoxide anions generated by hypoxanthine and xanthine oxidase as well as hydrogen peroxide increased LOX-1 mRNA expression in cultured aortic endothelial cells. Homocysteine, an atherogenic substance believed to exert its effects through oxidative stress, enhanced endothelial LOX-1 gene expression, which was suppressed by N-acetylcysteine. Second, rats receiving angiotensin II for 10 days manifested hypertension and LOX-1 upregulation in aortic endothelium via AT1 receptor. Tempo, a superoxide dismutase mimetic, alleviated LOX-1 augmentation induced by angiotensin II. These results indicated redox-sensitive upregulation of LOX-1 mRNA in both in vitro and in vivo systems, suggesting its potential role in atherosclerosis.
 ...
PMID:Redox-sensitive regulation of lox-1 gene expression in vascular endothelium. 1123 17

This study was performed to assess the significance of association between coronary artery disease (CAD) and circulating homocysteine concentrations. 100 consecutive CAD patients (78 men and 22 women, aged 31 to 79 years) qualified for PTCA were investigated. At the time of PTCA, the risk factors for CAD and plasma for homocysteine and vitamins were obtained. The controls were without clinical evidence of coronary artery disease and hypertension (90 men and 30 women aged 32 to 81 years). Homocysteine was assayed using ELISA test. Red cell folate and plasma vitamin B12 were assayed by immunofluoroscency (Delphia test). Homocysteine concentrations were higher in patients than in controls (13.61 +/- 4.5 vs 10.99 +/- 4.49 mumol/L, p < 0.001, adjusted for age). Male patients had nonsignificantly higher homocysteine levels than females (13.94 +/- 5.21 vs 11.46 +/- 5.16 mumol/L, p = 0.05, adjusted for age). Elevated homocysteine level--defined as one in the top fifth of the control distribution > or = 12.83 mumol/L--was seen in 46% of the patients compared with 20% of the control group (p = 0.001). The odds ratio (OR) for CAD in persons with elevated homocysteine level was 3.1 (95% Cl 1.6-5.8, p < 0.001, adjusted for age). The OR for CAD of 5 mumol/L increment in homocysteine level was 2.1 (95% Cl 1.4-3.1 p < 0.001, adjusted for age). After adjustment for conventional risk factors (age, smoking, hypertension, family history of CAD, hyperlipidemia), elevated homocysteine level remained independent risk factor for CAD (OR 2.88, 95% Cl 1.1-7.8, p < 0.05). We observed inverse correlation between homocysteine and folate level (r = -0.32, p = 0.005) and between homocysteine and vitamin B12 concentrations (r = -0.24, p = 0.03), especially in men. Patients with elevated homocysteine level had lower levels of folate (629.6 +/- 241.2 nmol/L vs 735.1 +/- 252.4 nmol/L, p < 0.05), and vitamin B12 (213.6 +/- 64.4 pmol/L vs 246.6 +/- 62.3 pmol/L, p < 0.05) than patients with normal level of homocysteine. Elevated plasma homocysteine level is a strong risk factor for coronary artery disease. A 5 mumol/L increment in total homocysteine level may be associated with twofold increase of risk for the disease.
 ...
PMID:[Elevated levels of homocysteine in plasma as a risk factor for coronary artery disease]. 1130 24

Serum homocysteine is increased, and correlates inversely with cognitive scores, in Alzheimer's disease (AD), vascular dementia and "age-associated memory impairment". Elevated levels might signal accelerated cognitive decline, although this remains to be established. We therefore repeated Mini-Mental State Examinations, together with additional ADAS-Cog assessments, in 32 healthy elderly individuals to determine whether prior homocysteine levels predicted cognitive changes over a 5-year period. Homocysteine predicted follow-up cognitive scores and rate of decline in cognitive performance independently of age, sex, education, renal function, vitamin B status, smoking and hypertension (p < 0.001). Homocysteine predicted word recall (p = 0.01), orientation (p = 0.02) and constructional praxis scores (p < 0.0001). One subject, with the second highest initial homocysteine, had developed probable AD at follow-up. Fasting total serum homocysteine appears to be an independent predictor of cognitive decline in healthy elderly and exerts a maximal effect on spatial copying skills.
 ...
PMID:Homocysteine and cognitive decline in healthy elderly. 1145 31

We tested if vitamin E, a fat-soluble antioxidant, prevents resistance vessel endothelial dysfunction caused by methionine-induced hyperhomocysteinemia in humans. Moderate elevations in plasma homocysteine concentrations are associated with atherosclerosis and hypertension. Homocysteine causes endothelial dysfunction possibly through several mechanisms. No previous study has tested if a fat-soluble antioxidant can prevent endothelial dysfunction caused by experimental hyperhomocysteinemia. Ten healthy subjects participated in a 2 x 2 factorial, double-blind crossover study, receiving L-methionine (100 mg/kg at -6 hours) or vehicle, with and without vitamin E (1,200 IU at -13 hours). Endothelial function of forearm resistance vessels was assessed using forearm blood flow responses to brachial artery administration of endothelium-dependent and endothelium-independent agents. Forearm resistance vessel dilatation to acetylcholine was significantly impaired 7 hours after methionine (placebo, 583 +/- 87% vs methionine 30 +/- 68%; p <0.05). Dilatation to bradykinin was also impaired (placebo, 509 +/- 54% vs methionine 289 +/- 48%; p <0.05). Methionine did not alter vasodilatation to the endothelium-independent vasodilators, nitroprusside, and verapamil. Methionine-induced impairment of resistance vessel dilatation to acetylcholine and bradykinin (p <0.05 vs placebo) was prevented by administration of vitamin E (acetylcholine, p = 0.004; bradykinin, p = 0.004; both vs methionine alone). Experimentally increasing plasma homocysteine concentrations by oral methionine rapidly impairs resistance vessel endothelial function in healthy humans and this effect is reversed with administration of the fat-soluble antioxidant, vitamin E.
 ...
PMID:Effect of vitamin E on resistance vessel endothelial dysfunction induced by methionine. 1147 9

Cardiovascular disease is the leading cause of mortality in Mexico, as well as in other Western countries. Conventional risk factors for atherosclerosis, such as cigarette smoking, systemic hypertension, diabetes mellitus, and hypercholesterolemia, do not explain this association completely. Recently, it has been recognized that hyperhomocysteinemia contributes to the atherosclerotic process, promoting endothelial damage and oxidative stress in the vascular wall. Homocysteine, an amino acid generated under physiologic conditions after ingestion of protein-rich foods, is used in a variety of metabolic pathways. Elevated plasma levels of this amino acid (higher than 15 mmol/L or lower in the presence of other cardiovascular risk factors) promote the development of atherosclerosis. Folic acid and vitamin B6 and B12 supplements decrease plasma levels of homocysteine effectively and may play an important role in the prevention and treatment of atherosclerotic vascular disease.
 ...
PMID:[Hyperhomocysteinemia. A new coronary risk factor]. 1151 57

Numerous clinical and epidemiological studies have identified elevated homocysteine levels in plasma as a risk factor for atherosclerotic vascular disease and thromboembolism. Hyperhomocysteinemia may develop as a consequence of defects in homocysteine-metabolizing genes; nutritional conditions leading to vitamin B(6), B(12), or folate deficiencies; or chronic alcohol consumption. Homocysteine is an intermediate in methionine metabolism, which takes place mainly in the liver. Impaired liver function leads to altered methionine and homocysteine metabolism; however, the molecular basis for such alterations is not completely understood. In addition, the mechanisms behind homocysteine-induced cellular toxicity are not fully defined. In the present work, we have examined the expression of the main enzymes involved in methionine and homocysteine metabolism, along with the plasma levels of methionine and homocysteine, in the liver of 26 cirrhotic patients and 10 control subjects. To gain more insight into the cellular effects of elevated homocysteine levels, we have searched for changes in gene expression induced by this amino acid in cultured human vascular smooth muscle cells. We have observed a marked reduction in the expression of the main genes involved in homocysteine metabolism in liver cirrhosis. In addition, we have identified the tissue inhibitor of metalloproteinases-1 and alpha1(I)procollagen to be upregulated in vascular smooth muscle cells and liver stellate cells exposed to pathological concentrations of homocysteine. Taken together, our observations suggest (1) impaired liver function could be a novel determinant in the development of hyperhomocysteinemia and (2) a role for elevated homocysteine levels in the development of liver fibrosis.
Hypertension 2001 Nov
PMID:Hyperhomocysteinemia in liver cirrhosis: mechanisms and role in vascular and hepatic fibrosis. 1171 26

Although the incidence of strokes is not maximal during sleeping hours, several lines of evidence make it probable that sleep in combination with breathing disorders like snoring and obstructive apneas are risk factors for ischemic strokes: the natural history of snoring and obstructive sleep apnea shows a higher incidence of strokes than in undisturbed sleep, the prevalence of snoring and sleep apneas in stroke patients is by far higher than in non-stroke patients; odds-ratios of stroke are higher in snorers and apneic patients than in normals, although the correction for confounders seems never perfect. The analysis of potential pathomechanisms linking sleep disordered breathing to strokes is another approach to the main topic: snoring and sleep apnea induce hypertension and arrhythmia, the carotid intima-media-thickness is increased, carotid atheromas are more common among apneics than among normals, the flow in the A. cerebri media is as well altered as the reaction to angiotensine II, noradrensine, isoproterenol and bradykinin. Homocysteine is increased, plasminogen activator inhibitor type 1 is inhibited and platelets are activated leading to an increased risk of thrombosis. There are no studies showing the effectiveness of treatment with nasal continuous positive airway pressure (nCPAP) on the rehabilitation of apneic stroke patients, but the outcome of non-apneic stroke patients is better than that of apneic stroke patients.
 ...
PMID:Sleep and stroke. 1192 38


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