Inhibitors of differentiation/DNA binding proteins Id1 and Id3 are regulated by statins in endothelial cells.
Id proteins (inhibitors of differentiation), which are involved in the control of cell cycle progression, can delay cellular differentiation and senescence and have been implicated in angiogenesis. The regulation of Id proteins in endothelial cells (ECs) by proangiogenic statins has not been investigated yet and remains unresolved. In this study, human dermal microvascular ECs (HDMECs) were stimulated with fluvastatin, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and serum in vitro. The regulation of Id1, Id3, p21, p27, and p53 and the phosphorylation of AKT was investigated by Western blotting. Id1 was up-regulated by fluvastatin and serum, but not by VEGF and HGF. Fluvastatin did not regulate p21 and p27, but down-regulated Id3 and p53 slightly. In contrast to VEGF and HGF, fluvastatin did not result in AKT phosphorylation, indicating that this pathway is not involved in the control of endothelial Id1 expression. These experiments demonstrate for the first time that Id1 can be up-regulated and p53 down-regulated by a statin in HDMECs. Regulation of these proteins in ECs may account for the proangiogenic effect of statins.
Pammer
J
J
Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria.
Reinisch
C
C
Kaun
C
C
Tschachler
E
E
Wojta
J
J
D001798:Blood Proteins / Q000494:pharmacology; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D051798:Inhibitor of Differentiation Protein 1; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012097:Repressor Proteins / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D001798:Blood Proteins; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005229:Fatty Acids, Monounsaturated; D006133:Growth Substances; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C497453:ID1 protein, human; D007211:Indoles; D051798:Inhibitor of Differentiation Protein 1; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C075640:ID3 protein, human; D000077340:Fluvastatin; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt