Homocysteine and the production of collagens, proliferation and apoptosis in human arterial smooth muscle cells.
Homocysteine (H(e)) is an important and independent risk factor for atherosclerosis. We showed that human aortic smooth muscles in cultures proliferated significantly at a concentration of 25 micromol/L H(e) without the presence of serum. There was no effect of H(e) on apoptosis as determined by TUNEL-assay and gene expression of proapoptotic protein bax, caspases and TNFalpha families. However, collagen types I, III and IV increased significantly in a dose-dependent manner at elevated concentrations of H(e) and the amount of type VI collagen was significantly reduced in a dose-dependent manner. H(e) induced increased cell replication with an unaffected apoptosis rate. The present observations suggest that H(e) may contribute to accelerated progression of atherosclerotic lesions with collagen alterations which transform the injury into fibrotic plaques.
Rasmussen
Lars M
LM
Research Laboratory for Biochemical Pathology, Aarhus Universitetshospital, 8000 Aarhus C, Denmark.
Hansen
Peter R
PR
Ledet
Thomas
T
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D006710:Homocysteine; D012313:RNA; D003094:Collagen