Journal
HYPERTENSION
Volume 38, Issue 5, Pages 1217-1221Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/hy1101.099499
Keywords
homocysteine; methionine; muscle, smooth, vascular; liver; cirrhosis; fibrosis; gene expression
Categories
Funding
- NIAAA NIH HHS [R0I AA-12677] Funding Source: Medline
Ask authors/readers for more resources
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 metalloprotemases-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available