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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homocysteine is increasingly recognized as a risk factor for atherothrombotic arterial diseases. We investigated the relation between plasma concentrations of total homocysteine (tHcy) and common carotid artery intima-media wall thickness, measured by B-mode ultrasonography, in 513 asymptomatic men and women from eastern Finland aged 45-69 years. The subjects were examined in 1994-95 at the baseline of the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study, a randomized double-blind placebo-controlled two by two factorial trial on the effect of vitamin E and C supplementation in the prevention of atherosclerotic progression. The subjects were assigned into two categories according to the plasma tHcy concentration; concentration over 11.5 micromol/L (highest quartile) or concentration below 11.5 micromol/L. In this study population the mean plasma tHcy concentration was 10.0 micromol/L, and the prevalence of plasma tHcy concentration exceeding 11.5 micromol/L was 33% in men and 18% in women. The adjusted mean intima-media thickness of the right and left common carotid arteries was 1.12 mm in men with elevated plasma tHcy concentration and 1.02 mm in men with a plasma tHcy concentration below 11.5 micromol/L (P = 0.029). In women there was no significant difference. We conclude that elevated plasma tHcy concentrations are associated with early atherosclerosis, as manifested by increased common carotid artery intima-media wall thickness, in middle-aged eastern Finnish men.
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PMID:Association between elevated plasma total homocysteine and increased common carotid artery wall thickness. 967 17

Homocysteine is a metabolite of methionine that may be remethylated by enzymes requiring folate and cobalamin (vitamin B12) to again form methionine or catabolized by the pyridoxine (vitamin B6) dependent enzyme, cystathionine beta synthase (CBS) to form cysteine (fig. 1) [1]. Homocysteine exists as a combination of various free and protein bound forms, but the total amount is what is usually measured and may be reported as homocyst(e)ine [2]. The biological plausibility that elevated homocysteine might lead to vascular disease noted in 1969 by McCully [3]. He reported that a child with abnormal cobalamin metabolism and hyperhomocysteinemia had arterial lesions similar to those seen in children with severe hyperhomocysteinemia from CBS deficiency. These findings led to the idea that moderate elevations in homocysteine, even those still within the so-called normal range, might also lead to vascular pathology through a variety of mechanisms including atherosclerosis and thrombosis [4].
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PMID:Homocysteine as a risk factor for ischemic stroke: an epidemiological story in evolution. 970 30

Homocysteine at abnormally high levels is an independent risk factor for atherosclerosis and may be a key factor in atherogenesis. Since homocysteine (Hcys) has been shown to promote cell proliferation and induction of the gene transcription factor c-fos in vascular smooth muscle cells (VSMCs), effects which can be mediated by MAP kinase, we hypothesized that homocysteine activates a MAP kinase-dependent signal transduction pathway. In this study, we find that homocysteine transiently activates MAP kinase (ERK2 isoform) in cultured VSMCs from chick embryos. Homocysteine activation of ERK2 is dose-dependent with an EC50 of approximately 500 nM and blocked by the MAP/Erk kinase (MEK) inhibitor PD98059. VSMC embryonic lineage is another determinant of homocysteine sensitivity. These findings demonstrate that homocysteine activates the MAP kinase signal transduction pathway and thus support the hypothesis that homocysteine may promote atherosclerosis by stimulation of growth promoting signal transduction pathways.
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PMID:ERK2 activation by homocysteine in vascular smooth muscle cells. 979 Sep 67

Fasting hyperhomocysteinemia is an independent risk factor for coronary artery disease, stroke, peripheral vascular atherosclerosis, and for arterial and venous thromboembolism. The risk for cardiovascular disease with homocysteine is similar to conventional risk factors. The interaction of hyperhomocysteinemia with hypertension and smoking is strong and the combined effect is more than multiplicative. The combined effect of homocysteine and cholesterol is additive. Homocysteine produces atherosclerosis, thromboembolism, and vascular endothelial cell injury. Vascular dysfunction produced by homocysteine may be due to endothelial cell damage. Homocysteinemia-induced atherosclerosis is probably due to various factors including endothelial cell injury, inability to sustain S-nitroso-homocysteine formation because of imbalance between production of nitric oxide by dysfunctional endothelium and homocysteine, smooth muscle cell proliferation, and thromboembolism. There is strong evidence that endothelial cell injury is associated with oxidative stress produced by homocysteine. Hyperhomocysteinemia is associated with numerous conditions, including coronary disease, stroke, peripheral vascular disease (carotid artery and cerebrovascular atherosclerosis), venous thrombosis, renal disease, diabetes mellitus, and organ transplant. Folic acid, vitamin B12 and B6 have been shown to be beneficial in reducing plasma homocysteine levels. Folic acid is specifically very effective, safe and inexpensive.
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PMID:Homocysteine, a Risk Factor for Cardiovascular Disease. 982 15

Elevated levels of plasma homocysteine may be an independent risk factor for coronary atherosclerosis. This study investigated whether plasma homocysteine levels are related to atherosclerotic lesions of saphenous vein grafts after coronary artery bypass surgery. Homocysteine levels were measured in fasting plasma by high-performance liquid chromatography and total cholesterol, triglyceride, high density lipoprotein cholesterol and lipoprotein (a) were also evaluated in 40 patients (mean age 65 +/- 8 years, mean interval after bypass surgery: 6.1 +/- 3.1 years, range 1-13 years). The vein graft disease group was defined as patients with angiographical stenosis of > or = 50% in any vein graft (n = 23). The other patients were defined as the no-vein graft disease group (n = 17). Patients who had a history of chronic renal failure or anatomic lesions of saphenous vein grafts were excluded. The distributions of homocysteine were skewed. Median homocysteine levels were 11.9 nmol/ml in all subjects. Homocysteine levels in the vein graft disease group were significantly higher than in the no-vein graft disease group (median 15.1 vs 10.6 nmol/ml, p = 0.01). In the analysis of plasma lipids, high-density lipoprotein cholesterol levels were significantly lower in the vein graft disease group than in the no-vein graft disease group (mean 37 +/- 11 vs 48 +/- 13 mg/dl, p = 0.01). Multiple regression analysis showed that elevated levels of homocysteine were an independent risk factor for saphenous vein graft disease after coronary artery bypass surgery. These findings indicate that elevated levels of plasma homocysteine are related to atherosclerotic lesions of saphenous vein grafts after coronary artery bypass surgery as well as coronary atherosclerosis.
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PMID:[Elevated levels of plasma homocysteine related to saphenous vein graft disease after coronary artery bypass graft surgery]. 991 52

Elevated plasma homocysteine is an independent risk factor for atherosclerosis and thrombosis. The exact mechanism by which homocysteine exerts its atherothrombotic action is still unclear. Accumulating evidence suggests that hyperhomocysteinaemia leads to endothelial injury and dysfunction, mediated by free radicals generated during the oxidation of homocysteine. Homocysteine also stimulates the proliferation of vascular smooth-muscle cells and inhibits the growth of vascular endothelial cells. Elevated homocysteine levels may also promote thrombosis by increased generation of thrombin. Other possible mechanisms for homocysteine-mediated atherogenesis include: the altered methylation of DNA and altered regulatory proteins associated with cell membrane, decreased bioavailability of nitric oxide, increased elastolysis and collagen accumulation, overstimulation of N-methyl-D-aspartate receptors and excessive adhesion of monocytes and neutrophils to endothelium. Understanding the mechanisms in vivo by which hyperhomocysteinaemia is associated with vascular disease may provide new approaches to prevention and treatment of atherothrombosis.
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PMID:Pathogenesis of vascular disease in hyperhomocysteinaemia. 991 72

In the present study, the levels of soluble adhesion molecules P- and E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and of other markers of endothelial activation or injury, such as thrombomodulin, von Willebrand factor (vWF), as well as homocysteine, were prospectively investigated in 71 patients (21 women, 50 men, age 68+/-13) with predominantly femoropopliteal peripheral arterial occlusive disease (PAOD, stage II-IV, Fontaine) before and after percutaneous transluminal angioplasty (PTA). Thirty patients (42.3%) developed restenosis within 6 months, defined as a > 50% reduction of the lumen diameter at the site of PTA. At entry in the study, 46% and 58% of all patients had higher than normal levels of soluble P-selectin and VCAM-1, respectively. Thrombomodulin (P < 0.01) measured at entry, was significantly higher in patients who developed late restenosis, with trends for higher values for P-selectin, VCAM-1 and vWF. The relative risks for developing restenosis were 2.41 (CI95%: 1.23-4.75) and 1.54 (CI95%: 0.98-2.72) for thrombomodulin and P-selectin, respectively. Soluble P-selectin and the severity of PAOD (Fontaine stage III/IV) were found to be statistically indicative factors for late restenosis in a logistic regression risk factor analysis with an overall predictive value of 72%. At 6 months, those who developed restenosis had also higher soluble P-selectin (P < 0.01), VCAM-1 (P < 0.05) and a trend for higher thrombomodulin. Homocysteine was elevated in 52% of the patients at entry but neither was it associated with higher restenosis rates nor did it correlate with the levels of thrombomodulin or the other adhesion molecules. These findings indicate that patients with PAOD have to a significant proportion, elevated levels of circulating soluble adhesion molecules and markers of endothelial activation occurring in concert with an ongoing atherosclerotic process.
Atherosclerosis 1999 Jan
PMID:Circulating cell adhesion molecules and endothelial markers before and after transluminal angioplasty in peripheral arterial occlusive disease. 992 May 21

Elevated plasma homocysteine levels may lead to an increased risk for atherosclerosis. Besides genetic factors a deficiency of folate, vitamin B6 and/or vitamin B12 may lead to an increase in the plasma concentration of this sulfur containing amino acid. Homocysteine may enhance by several direct and/or indirect mechanisms the pathogenesis of atherosclerosis. In this review selected aspects of homocysteine in relation to clinical practice will be discussed.
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PMID:[Homocysteine: a cardiovascular risk factor?]. 1009 46

Elevated plasma homocysteine levels are associated with vascular disease and thrombosis. Premature atherosclerosis and thromboembolism are seen in children who are homozygotes for defects in enzymes responsible for the metabolism of homocysteine. Adults with heterozygous defects have less marked elevations of homocysteine, and onset of atherosclerosis and vascular disease are delayed into the fourth and fifth decade of life. Homocysteine can damage vascular endothelium, cause proliferation of vascular smooth muscle, activate platelets, promote lipid peroxidation, and activate the coagulation cascade. Epidemiologic studies have linked elevations in plasma homocysteine with coronary artery disease, cerebrovascular disease, and thromboembolism. Folic acid, in combination with vitamins B6 and B12, can normalize homocysteine levels in most patients. Although randomized trials assessing the efficacy of homocysteine reduction have yet to be completed, treatment with vitamin supplementation should be considered in all patients at risk for vascular disease.
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PMID:Homocysteine: evidence for a causal relationship with cardiovascular disease. 1034 72

Homocysteine is a sulfhydryl amino acid formed during metabolism of methionine. Increasing evidence suggests that homocyst(e)ine may act as an independent risk factor for ischemic heart disease, cerebrovascular disease, and peripheral arterial disease. Recent prospective data have shown that homocyst(e)ine levels in the top 20% of the population increase the risk for ischemic heart disease by approximately twofold. Homocyst(e)ine seems to promote the progression of atherosclerosis by causing endothelial dysfunction, increasing oxidant stress, and promoting vascular smooth muscle growth. Recent human studies using methionine loading to experimentally induce moderate hyperhomocyst(e)inemia have demonstrated rapid and profound impairment of resistance and conduit artery endothelial function. No data are available from randomized, controlled trials of the effects of lowering plasma homocyst(e)ine on atherosclerotic vascular events; however, screening for hyperhomocyst(e)inemia should be actively considered in individuals with progressive and unexplained atherosclerosis. Both fasting and postmethionine load homocyst(e)ine levels should be measured. B vitamins, including folic acid and vitamins B6 and B12 are the mainstay of treatment of patients with hyperhomocyst(e)inemia. Primary prevention strategies await the completion of long-term, randomized, prospective studies.
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PMID:Homocysteine as a novel risk factor for atherosclerosis. 1044 7


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