title: Hyperhomocysteinemia and cardiovascular disease in uremia: the newest evidence in epidemiology and mechanisms of action.
abstract: In the general population, hyperhomocysteinemia is an independent risk factor for cardiovascular disease (ischemic disease, such as stroke and myocardial infarction, and arterial and venous thrombosis). We can presume that the association is causal, based on the example of homocystinuria, and on the evidence put forward by several basic science and epidemiologic studies. However, the results of large intervention trials, which may grant further support to this hypothesis, are not yet available. In chronic renal failure and in uremia, the evidence that is offered by carefully performed prospective studies also indicate the presence of an association, although some studies suggest reverse epidemiology. The mechanisms underlying the association, and able to explain the several toxic effects of homocysteine, related or not to cardiovascular disease, are unclear. Oxidation, nitrosylation, and hypomethylation are among the postulated mechanisms. In uremia, protein hypomethylation interferes with protein repair; DNA hypomethylation impairs regulation of gene expression, whereas folate treatment reverts such alterations. Acylation, another structural modification able to impair protein function, is a possible mediator of homocysteine toxicity.
authors.affiliation: First Division of Nephrology, Department of Pediatrics, Second University of Naples, Naples, Italy. alessandra.perna@unina2.it
authors.forename: Alessandra F
authors.initials: AF
authors.lastname: Perna
authors.forename: Filomena
authors.initials: F
authors.lastname: Acanfora
authors.forename: Ersilia
authors.initials: E
authors.lastname: Satta
authors.forename: Cinzia
authors.initials: C
authors.lastname: Lombardi
authors.forename: Diego
authors.initials: D
authors.lastname: Ingrosso
authors.forename: Natale G
authors.initials: NG
authors.lastname: De Santo
mesh_terms: D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000453:epidemiology / Q000209:etiology*; D007676:Kidney Failure, Chronic / Q000150:complications*; D014511:Uremia / Q000150:complications*