title: The CCR5 chemokine receptor mediates vasoconstriction and stimulates intimal hyperplasia in human vessels in vitro.
abstract: OBJECTIVE
  The chemokine receptor CCR5 and its inflammatory ligands have been linked to atherosclerosis, an accelerated form of which occurs in saphenous vein graft disease. We investigated the function of vascular smooth muscle CCR5 in human coronary artery and saphenous vein, vascular tissues susceptible to atherosclerosis, and vasospasm.
  
  
  RESULTS
  CCR5 ligands were vasoconstrictors in saphenous vein and coronary artery. In vein, constrictor responses to CCL4 were completely blocked by CCR5 antagonists, including maraviroc. CCR5 antagonists prevented the development of a neointima after 14 days in cultured saphenous vein. CCR5 and its ligands were expressed in normal and diseased coronary artery and saphenous vein and localized to medial and intimal smooth muscle, endothelial, and inflammatory cells. [(125)I]-CCL4 bound to venous smooth muscle with KD = 1.15 ± 0.26 nmol/L and density of 22 ± 9 fmol mg(-1) protein.
  
  
  CONCLUSIONS
  Our data support a potential role for CCR5 in vasoconstriction and neointimal formation in vitro and imply that CCR5 chemokines may contribute to vascular remodelling and augmented vascular tone in human coronary artery and vein graft disease. The repurposing of maraviroc for the treatment of cardiovascular disease warrants further investigation.
authors: Clinical Pharmacology Unit, Level 6 ACCI, Box 110 Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors: Janet J
authors: JJ
authors: Maguire
authors: Katie L
authors: KL
authors: Jones
authors: Rhoda E
authors: RE
authors: Kuc
authors: Murray C H
authors: MC
authors: Clarke
authors: Martin R
authors: MR
authors: Bennett
authors: Anthony P
authors: AP
authors: Davenport
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000098:blood supply* / Q000473:pathology; D009924:Organ Culture Techniques; D019713:Receptors, CCR5 / Q000378:metabolism*; D012501:Saphenous Vein / Q000378:metabolism* / Q000473:pathology; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: C584933:CCR5 protein, human; D018925:Chemokines; D019713:Receptors, CCR5
keywords: CCR5; Human coronary artery; Maraviroc; Saphenous vein graft disease; Vasoconstriction