title: Curcumin inhibits platelet-derived growth factor-stimulated vascular smooth muscle cell function and injury-induced neointima formation.
abstract: OBJECTIVE
  Vascular smooth muscle cell (VSMC) migration, proliferation, and collagen synthesis are key events involved in the pathogenesis of cardiovascular disease. Growth factors, such as platelet-derived growth factor (PDGF) and fibroblast growth factor, released during vascular injury plays a pivotal role in regulating these events. Curcumin (diferuloyl methane), a major component of the spice turmeric (Curcuma longa), has been shown recently to have beneficial effects in chronic conditions, such as inflammation, cancer, cystic fibrosis, and Alzheimer's disease. The objective of this study was to investigate the ability of curcumin to inhibit PDGF-stimulated migration, proliferation, and collagen synthesis in cultured VSMCs and neointima formation after carotid artery injury in rats.
  
  
  RESULTS
  Curcumin (1 to 25 microM) produced a concentration-dependent inhibition of PDGF-elicited VSMC migration, proliferation, and collagen synthesis assessed by chemotaxis, [3H]thymidine incorporation, and [3H]-L-proline incorporation, respectively. Curcumin blocked PDGF-induced VSMC actin-cytoskeleton reorganization, attenuated PDGF signal transduction, and inhibited the binding of PDGF to its receptors. Carotid artery neointima formation was significantly attenuated by perivascular curcumin compared with vehicle controls 14 days after injury, characterized by reduced DNA synthesis, collagen synthesis, and PDGF receptor phosphorylation.
  
  
  CONCLUSIONS
  These data suggest that curcumin is a potent inhibitor of key PDGF-stimulated VSMC functions and may play a critical role in regulating these events after vascular injury.
authors.affiliation: Division of Pharmaceutical Sciences, Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071-3375, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Yang
authors.forename: D Paul
authors.initials: DP
authors.lastname: Thomas
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhang
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Culver
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Alexander
authors.forename: William J
authors.initials: WJ
authors.lastname: Murdoch
authors.forename: Mysore N A
authors.initials: MN
authors.lastname: Rao
authors.forename: David A
authors.initials: DA
authors.lastname: Tulis
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Nair
authors.initials: N
authors.lastname: Sreejayan
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000166:cytology; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D004347:Drug Interactions; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010982:Platelet-Derived Growth Factor; D014443:Tyrosine; D003094:Collagen; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D003474:Curcumin