The effects of HMG-CoA reductase inhibitor on vascular progenitor cells.
Circulating bone marrow-derived vascular progenitor cells contribute to angiogenesis, atherosclerosis, and the response to vascular injury. These vascular progenitor cells consist of two cell groups, endothelial progenitor cells (EPCs) and smooth muscle progenitor cells (SMPCs). Although HMG-CoA reductase inhibitors (statins) have been reported to inhibit atherosclerosis partially by increased EPCs, the effects of statins on SMPCs are unclear. Therefore, we investigated the relationship between EPCs and SMPCs and whether pravastatin has atheroprotective effects on SMPCs. Peripheral mononuclear cells (MNCs) were isolated and cultured on fibronectin-coated dishes in SMPC medium. MNCs were stained with acetylated low density lipoprotein and lectin, or alpha-smooth muscle actin, and cell numbers were counted. mRNA expression and vascular endothelial growth factor (VEGF) protein synthesis of MNCs were evaluated. Pravastatin significantly increased the number of EPC and decreased the number of SMPC. mRNA expression of VEGF, endothelial nitric oxide synthase, VEGF receptor-2 (KDR), and Akt were up-regulated, and VEGF secretion was increased by pravastatin. The present study demonstrated that pravastatin has promotive effects on the differentiation from MNCs to EPC cells, while inhibitory effects to SMPC cells. Our findings suggest a previously unreported mechanism of the effect of statin therapy on vascular progenitor cells.
Kusuyama
Takanori
T
Department of Internal Medicine and Cardiology, Osaka City University Medical School, Japan.
Omura
Takashi
T
Nishiya
Daisuke
D
Enomoto
Soichiro
S
Matsumoto
Ryo
R
Murata
Takashi
T
Takeuchi
Kazuhide
K
Yoshikawa
Junichi
J
Yoshiyama
Minoru
M
D000199:Actins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D037102:Lectins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D017035:Pravastatin / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
D000199:Actins; D017077:Culture Media, Conditioned; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D037102:Lectins; D008077:Lipoproteins, LDL; D052250:Nitric Oxide Synthase Type III; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017035:Pravastatin; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C032629:acetyl-LDL; C498862:Acta2 protein, rat