Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
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Hieronim Jakubowski
Abstract
Metabolic conversion of homocysteine (Hcy) to a chemically reactive metabolite, Hcy-thiolactone, catalyzed by methionyl-tRNA synthetase is the first step in a pathway that is suggested to contribute to Hcy toxicity in humans. The accumulation of Hcy-thiolactone is detrimental because of its intrinsic ability to modify proteins by forming N-Hcy-protein adducts, in which a carboxyl group of Hcy is N-linked to the ε-amino group of a protein lysine residue. N-linked Hcy occurs in each protein examined and constitutes a significant pool of Hcy in the blood. N-Hcy proteins are likely to be recognized as neo-self antigens and induce an autoimmune response. Indeed, we found that autoantibodies specific for an Nε-Hcy-Lys epitope on N-Hcy-proteins occur in humans. Serum levels of anti-N-Hcy-protein autoantibodies are directly correlated with plasma tHcy, but not with plasma cysteine or methionine levels. In a group of male patients with stroke, levels of anti-N-Hcy-protein autoantibodies and tHcy were significantly higher than in a group of healthy subjects. In a group of male patients with angiographically documented coronary artery disease, seropositivity for anti-N-Hcy-protein autoantibodies occurred five-fold more frequently than in controls and was an independent predictor of coronary artery disease. These findings show that the formation of N-Hcy-proteins has important physiological consequences and support a hypothesis that N-Hcy-protein is a neo-self antigen that contributes to immune activation, an important modulator of atherogenesis.
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©2005 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Homocysteine research – where do we stand and where are we going?
- Hyperhomocysteinemia and arteriosclerosis: historical perspectives
- Homocysteine and heart failure: a review of investigations from the Framingham Heart Study
- Homocysteine and vascular disease in diabetes: a double hit?
- Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia
- Effects of homocysteine on vascular and tissue adenosine: a stake in homocysteine pathogenicity?
- Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
- Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients
- Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy
- Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
- Hyperhomocysteinemia and macromolecule modifications in uremic patients
- Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin treatment in renal patients
- Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population
- Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects
- Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project
- A laboratory algorithm with homocysteine as the primary parameter reduces the cost of investigation of folate and cobalamin deficiency
- Betaine: a key modulator of one-carbon metabolism and homocysteine status
- Molecular targeting by homocysteine: a mechanism for vascular pathogenesis
- Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
- Homocysteine in relation to cognitive performance in pathological and non-pathological conditions
- Homocysteine and B vitamins in mild cognitive impairment and dementia
- Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study
- Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions
- Homocysteine – a newly recognised risk factor for osteoporosis
- Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women
- Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality
- Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance
- Concentrations of homocysteine, related metabolites and asymmetric dimethylarginine in preeclamptic women with poor nutritional status
- Asymmetric dimethylarginine, homocysteine and renal function – is there a relation?
- Interactions between folate and aging for carcinogenesis
- The potential cocarcinogenic effect of vitamin B12 deficiency
- The vegetarian lifestyle and DNA methylation
Articles in the same Issue
- Homocysteine research – where do we stand and where are we going?
- Hyperhomocysteinemia and arteriosclerosis: historical perspectives
- Homocysteine and heart failure: a review of investigations from the Framingham Heart Study
- Homocysteine and vascular disease in diabetes: a double hit?
- Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia
- Effects of homocysteine on vascular and tissue adenosine: a stake in homocysteine pathogenicity?
- Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
- Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients
- Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy
- Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
- Hyperhomocysteinemia and macromolecule modifications in uremic patients
- Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin treatment in renal patients
- Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population
- Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects
- Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project
- A laboratory algorithm with homocysteine as the primary parameter reduces the cost of investigation of folate and cobalamin deficiency
- Betaine: a key modulator of one-carbon metabolism and homocysteine status
- Molecular targeting by homocysteine: a mechanism for vascular pathogenesis
- Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
- Homocysteine in relation to cognitive performance in pathological and non-pathological conditions
- Homocysteine and B vitamins in mild cognitive impairment and dementia
- Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study
- Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions
- Homocysteine – a newly recognised risk factor for osteoporosis
- Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women
- Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality
- Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance
- Concentrations of homocysteine, related metabolites and asymmetric dimethylarginine in preeclamptic women with poor nutritional status
- Asymmetric dimethylarginine, homocysteine and renal function – is there a relation?
- Interactions between folate and aging for carcinogenesis
- The potential cocarcinogenic effect of vitamin B12 deficiency
- The vegetarian lifestyle and DNA methylation
