title: Salvianolic acid A inhibits PDGF-BB induced vascular smooth muscle cell migration and proliferation while does not constrain endothelial cell proliferation and nitric oxide biosynthesis.
abstract: Proliferation and migration of vascular smooth muscle cells (VSMCs) are critical events in the initiation and development of restenosis upon percutaneous transluminal coronary angioplasty (PTCA). Polyphenols have been suggested to ameliorate post-angioplasty restenosis. Salvianolic A (SalA) is one of the most abundant polyphenols extracted from salvia. In this study, we investigated the effect of salvianolic A (SalA) on the migration and proliferation of VSMCs. We found a preferential interaction of SalA with cellular systems that rely on the PDGF signal, but not on the EGF and bFGF signal. SalA inhibits PDGF-BB induced VSMC proliferation and migration in the concentration range from 0.01 to 0.1 μM. The inhibition of SalA on VSMC proliferation is associated with cell cycle arrest. We also found that SalA inhibits the PDGFRβ-ERK1/2 signaling cascade activated by PDGF-BB in VSMCs. In addition, SalA does not influence the proliferation of endothelial cells, the synthesis of NO and eNOS protein expression. Our results suggest that SalA inhibits migration and proliferation of VSMCs induced by PDGF-BB via the inhibition of the PDGFRβ-ERK1/2 cascade, but that it does not constrain endothelial cell proliferation and nitric oxide biosynthesis. Thus, the present study suggests a novel adjunct pharmacological strategy to prevent angioplasty-related restenosis.
authors.affiliation: Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Sun
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Tiantai
authors.initials: T
authors.lastname: Zhang
authors.forename: Wenyu
authors.initials: W
authors.lastname: Xin
authors.forename: Xi
authors.initials: X
authors.lastname: Lan
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
mesh_terms: D000818:Animals; D000077214:Becaplermin; D002109:Caffeic Acids / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007773:Lactates / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017479:Receptors, Platelet-Derived Growth Factor / Q000819:agonists / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D015815:Cell Adhesion Molecules; D007773:Lactates; D020574:Proto-Oncogene Proteins c-sis; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D009569:Nitric Oxide; C066201:salvianolic acid A; D004815:Epidermal Growth Factor; D052250:Nitric Oxide Synthase Type III; D017479:Receptors, Platelet-Derived Growth Factor