Vascular smooth muscle cell activation and growth by 4-hydroxynonenal.
The present study examines the signal transduction mechanism that is involved in the growth of vascular smooth muscle cells exposed to 4-hydroxynonenal (HNE) in vitro. This aldehyde component of oxidized low-density lipoprotein has been identified in atherosclerotic lesion. Exposure to HNE caused ERK, JNK, and p38 MAP kinase activation as well as the induction of c-fos and c-jun gene expression. AP-1 activity was also significantly induced by HNE treatment. These intracellular activities appear to be the mechanism of HNE-caused mitogenesis. Indeed, HNE induced vascular smooth muscle cell proliferation as determened by Alamar-Blue assay and stimulated DNA synthesis as determined by bromodeoxyuridine incorporation. These observations are consistent with a role of lipid peroxidation products in vascular smooth muscle cell growth in atherogenesis.
Kakishita
H
H
Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Hattori
Y
Y
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000096:biosynthesis / Q000235:genetics
D000447:Aldehydes; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D004247:DNA; D020928:Mitogen-Activated Protein Kinases; C027576:4-hydroxy-2-nonenal