title: Comparison of doxycycline and minocycline in the inhibition of VEGF-induced smooth muscle cell migration.
abstract: Smooth muscle cell migration plays an important role during angiogenesis and vascular remodeling. In this study, we examined the effects of doxycycline and minocycline on vascular endothelial growth factor (VEGF)-induced human aortic smooth muscle cell (HASMCs) migration, and explored the mechanisms in which doxycycline or minocycline inhibit HASMC migration. We demonstrated that both doxycycline and minocycline attain consistent anti-angiogenic effects in the inhibition of HASMC migration via a different signal pathway (p<0.05). This effect is through attenuating VEGF-induced matrix metalloproteinase-9 (MMP-9) activity (p<0.05). Doxycycline could increase tissue inhibitors of metalloproteinases-1 (TIMP-1) expression while minocycline down-regulated PI3K/Akt phosphorylation in HASMC. Our study suggests that doxycycline has a stronger ability to inhibit MMP secretion in HASMC by up-regulating endogenous MMPs inhibitor TIMP-1, while minocycline implements anti-angiogenic effect through inhibiting HASMC migration by down-regulating PI3K/Akt pathway.
authors.affiliation: Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California-San Francisco, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
authors.forename: Jianhua S
authors.initials: JS
authors.lastname: Yao
authors.forename: Fanxia
authors.initials: F
authors.lastname: Shen
authors.forename: William L
authors.initials: WL
authors.lastname: Young
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Yang
mesh_terms: D001483:Base Sequence; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D017931:DNA Primers; D004318:Doxycycline / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D008911:Minocycline / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D017931:DNA Primers; D061965:Matrix Metalloproteinase Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008911:Minocycline; D004318:Doxycycline