The role of secondary growth factor production in thrombin-induced proliferation of vascular smooth muscle cells.
Alpha-thrombin is a multifunctional serine proteinase that is concentrated at sites of vascular injury and has been implicated in vascular healing responses following balloon injury. In addition to its well-known hemostatic effects, thrombin stimulates smooth muscle cell (SMC) proliferation via binding of protease activated receptor-1 (PAR-1), a seven transmembrane, G-protein-coupled cell surface receptor. Following activation of this receptor, SMC produce and secrete various autocrine growth factors, including platelet-derived growth factor-AA (PDGF-AA), basic fibroblast growth factor (bFGF), heparin binding epidermal growth factor (HBEGF), and transforming growth factor-beta (TGFbeta). The role that autocrine growth factors play in alpha-thrombin-induced proliferation will be discussed in this review.
Stouffer
G A
GA
Department of Medicine and The Sealy Center for Molecular Cardiology, University of Texas Medical Branch, Galveston 77555-1064, USA.
Runge
M S
MS
D000789:Angina, Unstable / Q000188:drug therapy; D000818:Animals; D000991:Antithrombins / Q000627:therapeutic use; D002404:Catheterization / Q000009:adverse effects; D002455:Cell Division / Q000187:drug effects; D002986:Clinical Trials as Topic; D004815:Epidermal Growth Factor / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D066257:Heparin-binding EGF-like Growth Factor; D024764:Hirudin Therapy; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000293:injuries / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D016032:Randomized Controlled Trials as Topic; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000187:drug effects / Q000502:physiology; D012008:Recurrence; D013917:Thrombin / Q000494:pharmacology / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D017211:Treatment Failure
D000991:Antithrombins; D006133:Growth Substances; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D016212:Transforming Growth Factor beta; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D013917:Thrombin