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

Vitamin B6 is effective in the treatment of carpal tunnel syndrome and related disorders in patients with vitamin B6 deficiency. Hyperhomocysteinemia, a risk factor for atherosclerosis, is associated with deficiencies of vitamin B6, folate, and cobalamin. Patients who were given vitamin B6 for carpal tunnel syndrome and other degenerative diseases were found to have 27% of the risk of developing acute cardiac chest pain or myocardial infarction, compared with patients who had not taken vitamin B6. Among elderly patients of the author (JE) expiring at home, the average age at death from myocardial infarction was 8 years later in those who had taken vitamin B6, compared with those who had not taken vitamin B6. The preventive effect of vitamin B6 on progression of coronary heart disease may be related to increased formation of pyridoxal phosphate, the coenzyme that is required for catabolism of the atherogenic amino acid, homocysteine.
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PMID:Prevention of myocardial infarction by vitamin B6. 855 75

Nitric oxide (NO) is associated with broad-spectrum antimicrobial activity of particular importance in infections caused by intracellular pathogens. An insertion mutation in the metL gene of Salmonella typhimurium conferred specific hypersusceptibility to S-nitrosothiol NO-donor compounds and attenuated virulence of the organism in mice. The metL gene product catalyzes two proximal metabolic steps required for homocysteine biosynthesis. S-Nitrosothiol resistance was restored by exogenous homocysteine or introduction of the metL gene on a plasmid. Measurement of expression of the homocysteine-sensitive metH gene indicated that S-nitrosothiols may directly deplete intracellular homocysteine. Homocysteine may act as an endogenous NO antagonist in diverse processes including infection, atherosclerosis, and neurologic disease.
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PMID:Homocysteine antagonism of nitric oxide-related cytostasis in Salmonella typhimurium. 860 31

Growing evidence suggests that moderately elevated levels of homocysteine are associated not only with arterial thrombosis and atherosclerosis but also with venous thrombosis as well. We have reviewed recent studies that indicate that homocysteine inhibits several different anticoagulant mechanisms that are mediated by the vascular endothelium. The protein C enzyme system appears to be one of the most important anticoagulant pathways in the blood. Homocysteine inhibits the expression and activity of endothelial cell surface thrombomodulin, the thrombin cofactor responsible for protein C activation. Homocysteine inhibits the antithrombin III binding activity of endothelial heparan sulfate proteoglycan, thereby suppressing the anticoagulant effect of antithrombin III. Homocysteine also inhibits the ecto-ADPase activity of human umbilical vein endothelial cells (HUVECS). Because ADP is a potent platelet aggregatory agent, this action of homocysteine is prothrombotic. Homocysteine also interferes with the fibrinolytic properties of the endothelial surface because it inhibits the binding of tissue plasminogen activator. Homocysteine stimulates HUVEC tissue factor activity. We have found that lipoprotein(a) [Lp(a)] also stimulates HUVEC tissue factor activity. The combination of Lp(a) plus homocysteine induced more tissue factor activity than either agent alone. These disruptions in several different vessel wall-related anticoagulant functions provide plausable mechanisms for the occurrence of thrombosis in hyperhomocysteinemia.
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PMID:Homocysteine and hemostasis: pathogenic mechanisms predisposing to thrombosis. 864 72

Hyperhomocysteinemia refractory to standard B-vitamin supplementation treatment persists in > or = 75% of maintenance dialysis patients, potentially increasing their risk for atherothrombotic sequelae. We examined whether predialysis administration of oral N-acetylcysteine (NAC), which acutely increases the non-protein bound, dialyzable fraction of plasma homocysteine, might augment the homocysteine-lowering effect of dialysis therapy. Predialysis and postdialysis total plasma homocysteine levels were determined on a control day, and on a day in which oral NAC (1200 mg) was administered predialysis in n = 11 maintenance hemodialysis patients. Although NAC treatment had no significant effect on hemodialysis removal of plasma homocysteine (P = 0.594), we observed a 16% reduction (P = 0.033) in non-fasting prehemodialysis total plasma homocysteine on the NAC treatment vs. non-treatment day. Longer term, placebo-controlled confirmation of this finding will be required to evaluate the possible chronic homocysteine-lowering efficacy of NAC treatment in hemodialysis patients.
Atherosclerosis 1996 Feb
PMID:Lack of effect of oral N-acetylcysteine on the acute dialysis-related lowering of total plasma homocysteine in hemodialysis patients. 864 65

Moderate hyperhomocysteinemia, a risk factor for premature atherosclerosis, is present in chronic uremic patients. We prospectively evaluated the effects of sequential supplementation with pyridoxine (70 mg/day) and folic acid (10 mg/day) for two 3-month periods in 37 nondialyzed patients (29 males) with creatinine clearance (CCr) ranging from 10 to 80 ml/min, whose plasma vitamin B12 and folate level was in the normal range. Mean (+/- SD) baseline plasma total homocysteine (Hcy) was 14.9 +/- 5.2, 16.5 +/- 5.1 and 26.1 +/- 12.1 mumol/l (upper limit in 45 healthy controls 14.1 mumol/l) in patients with CCr 40-80, 20-40 and < 20 ml/min, respectively. Following pyridoxine Hcy did not significantly decrease whereas following folic acid Hcy decreased significantly to 9.9 +/- 2.9 (-33% vs. baseline), 10.3 +/- 3.4 (-37%) and 15.4 +/- 5.5 (-40%), respectively (Student's paired t test, p < 0.001) in the 3 groups. We conclude that folate (but not pyridoxine) pharmacologic supplementation is effective in lowering elevated plasma Hcy in chronic renal failure patients, thus suggesting that enhancing the Hcy remethylation pathway may overcome hyperhomocysteinemia in such patients. In view of the potential atherogenic effects of hyperhomocysteinemia, long-term folate supplementation should be considered in uremic patients.
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PMID:Long-term folic acid (but not pyridoxine) supplementation lowers elevated plasma homocysteine level in chronic renal failure. 867 98

To assess the relationship between risk factors for cardiovascular disease and early atherosclerotic changes in the carotid artery, we measured carotid intima-media thickness by B-mode ultrasonography in 61 boys and 29 girls 10 to 19 years old with familial hypercholesterolemia (FH) and 30 control subjects matched for age and sex. All were nonsmokers, and all the FH adolescents had a known mutation in the LDL receptor gene. Mean intima-media thickness in the far wall of the carotid bulb was greater (P = .03) in the FH group than in the control subjects: 0.54 mm (95% confidence interval [CI], 0.52 to 0.56) versus 0.50 mm (95% CI, 0.47 to 0.52). In the entire group, mean and maximum intima-media thicknesses in the carotid bulb were positively associated with levels of apolipoprotein B and fibrinogen after control for pubertal stage (r = .19 to .24; P < .05), as was male sex. Plasma total homocysteine was similar in the FH and control groups and was associated with mean and maximum intima-media thicknesses in the far wall of the common carotid artery and carotid bulb after control for pubertal stage (r = .22 to .28; P < .05). With the exception of the relation between plasma fibrinogen level and mean carotid bulb intima-media thickness, these associations were essentially unchanged in stepwise multiple linear regression analyses, allowing for the entry of BMI and level of HDL cholesterol into the analysis. Carotid artery plaque was present in 10% of the children with FH versus none of the control subjects. Children with plaque had a higher mean cholesterol-years score than children without plaque. These findings suggest that the classic lipid and hemostatic risk factors as well as plasma total homocysteine are associated with markers of early carotid atherosclerosis from the second decade of life. B-mode ultrasonography may prove to be a useful tool in risk stratification of children with FH.
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PMID:Risk factors related to carotid intima-media thickness and plaque in children with familial hypercholesterolemia and control subjects. 869 63

A short survey is presented of the homocysteine theory of atherosclerosis with the key role of endothelial injury. Hyperhomocysteinaemia is a newly emerging risk factor of atherosclerosis. Both hereditary and nutritional influences may contribute to its occurrence. As this risk factor concerns 30-50 percent of atherosclerotics, it may be expected that new methods making possible its detection will be developed and routinely used. Beside the determination of homocysteine blood levels some indicators of endothelial dysfunction such as endothelaemia after methionine load may be used in the future.
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PMID:Homocysteine theory of atherosclerosis. 871 12

We compared biochemical and molecular methods for the identification of heterozygous carriers of mutations in the cystathionine beta-synthase (CBS) gene. Eleven relatives of seven unrelated patients with homocystinuria due to homozygous CBS deficiency and controls were studied with respect to total homocysteine concentrations before and after methionine loading. In addition, we determined CBS activity in cultured skin fibroblasts and tested for the presence of five known mutations by a PCR-based method in these seven patients, their relatives and controls. The results demonstrate that measurement of homocysteine after methionine loading and assay of CBS enzyme activity in cultured fibroblasts identify most but not all heterozygotes. There was significant correlation between homocysteine concentrations and CBS activities only after methionine loading (r = 0.12, 0.48, 0.48 and 0.50 at 0, 4, 6 and 8 h, respectively). Among the homozygous patients, molecular approaches identified five T833C and two G919A mutations out of 14 independent alleles, confirming the studies of others that these represent the two most prevalent mutations. In addition, we found that three of six heterozygotes with the T833 C allele had post-methionine loading homocysteine levels which overlapped with controls and of the other three, one (as well as an obligate heterozygote who did not carry any of the five mutant alleles tested) had CBS activity comparable to that of controls. These findings demonstrate that genotyping is useful as an adjunctive method for the diagnosis of the heterozygous carrier state of CBS deficiency.
Atherosclerosis 1996 Apr 26
PMID:Molecular and biochemical approaches in the identification of heterozygotes for homocystinuria. 872 13

It has been shown that serum total homocysteine (HC) is a risk factor for vascular disease which characterizes endothelial damage. The incidence of vascular disease is increased in continuous ambulatory peritoneal dialysis (CAPD) patients. Our aim was to investigate: (1) whether concentration of HC correlates with atherosclerotic and inflammatory events, and (2) if fish oil therapy can retard the disturbance in lipid metabolism which promotes atherosclerosis. Fourteen patients with various degrees of impaired peritoneal clearance and lipid metabolism were observed. In all patients the serum HC was elevated. Seven patients were treated with fish oil for three months. The results indicate an average increase of HC (+18%), total cholesterol (+6.6%), aggregation of erythrocytes (+9%), and an average decrease of dialysate-to-plasma creatinine (D/P) ratio (-7%), deformability of erythrocytes (-8%), and normalization of elevated soluble interleukin-2 receptor (sIL-2R) values. Regression analysis of all data demonstrated a significant correlation between HC and parameters of lipid metabolism and hemorheology. There were no significant correlations between HC and peritoneal function and serum cytokine levels. We conclude that the treatment in CAPD patients with fish oil did not improve the lipid metabolism disturbances in atherosclerosis and peritoneal function. Elevated HC confirms the progression of the disease.
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PMID:Increased serum level of total homocysteine in CAPD patients despite fish oil therapy. 872 1

In response to homocysteine induced toxicity in human umbilical vein endothelial cells, minimal changes in the concentration of cellular protein thiols but substantial changes in the concentration of intracellular soluble thiols were observed. The latter correlated closely with changes in cellular glutathione levels. No correlation existed between cellular glutathione levels and cell viability, whereas a close correlation between NAD+ levels and cell viability was demonstrated. Large decreases in cellular NAD+ occurred in response to homocysteine induced toxicity which were accompanied by the production of single stranded DNA. 3-Aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase preserved cell viability and cellular NAD+ levels. Evidence that DNA synthesis was also compromised was revealed by the decreased capacity of homocysteine treated cells to incorporate deoxyuridine. Radical scavengers were also effective in preventing homocysteine induced toxicity. It is likely that the major threat to cells derives from radicals generated intracellularly. Eicosanoid metabolism and the xanthine oxidase system have been identified as two potential sources of radicals.
Atherosclerosis 1996 May
PMID:Homocysteine mediated endothelial cell toxicity and its amelioration. 876 80


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