Homocysteine as a Risk Factor for Vascular Disease
- 1 October 1997
- journal article
- research article
- Published by Wolters Kluwer Health in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 17 (10), 2074-2081
- https://doi.org/10.1161/01.atv.17.10.2074
Abstract
An increased plasma homocysteine level is an independent risk factor for vascular disease. However, the pathological mechanisms by which homocysteine promotes atherosclerosis are not yet clearly defined. Arterial smooth muscle cells cultured in the presence of homocysteine grew to a higher density and produced and accumulated collagen at levels significantly above control values. Homocysteine concentrations as low as 50 μmol/L significantly increased both cell density and collagen production. Cell density increased by as much as 43% in homocysteine-treated cultures. Homocysteine increased collagen production in a dose-dependent manner. Smooth muscle cells treated with homocysteine at concentrations observed in patients with hyperhomocysteinemia had collagen synthesis rates as high as 214% of control values. Likewise, collagen accumulation in the cell layer was nearly doubled in homocysteine-treated cultures. Addition of aquacobalamin to homocysteine-treated cultures controlled the increase in smooth muscle cell proliferation and collagen production. These results indicate a cellular mechanism for the atherogenicity of homocysteine and provide insight into a potential preventive treatment.Keywords
This publication has 56 references indexed in Scilit:
- A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductaseNature Genetics, 1995
- Homocysteine metabolism and the oxidative modification of proteins and lipidsFree Radical Biology & Medicine, 1993
- Synthesis of homocysteine thiolactone by methionyl‐tRNA synthetase in cultured mammalian cellsFEBS Letters, 1993
- Cell density and proliferation modulate collagen synthesis and procollagen mRNA levels in arterial smooth muscle cellsExperimental Cell Research, 1992
- Hyperhomocysteinemia: An Independent Risk Factor for Vascular DiseaseNew England Journal of Medicine, 1991
- Neuropsychiatric Disorders Caused by Cobalamin Deficiency in the Absence of Anemia or MacrocytosisNew England Journal of Medicine, 1988
- Oxidation of low-density lipoprotein by thiol compounds leads to its recognition by the acetyl LDL receptorBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1987
- Homocystinuria and Megaloblastic Anemia Responsive to Vitamin B12TherapyNew England Journal of Medicine, 1984
- Effect of Induced Elevated Plasma Levels of Homocystine and Methionine in Rats on Collagen and Elastin StructuresConnective Tissue Research, 1976
- Use of a mixture of proteinase-free collagenases for the specific assay of radioactive collagen in the presence of other proteinsBiochemistry, 1971