title: Adenosine A₂B receptor agonism inhibits neointimal lesion development after arterial injury in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  The A(2B) adenosine receptor (A(2B)R) is highly expressed in macrophages and vascular smooth muscle cells and has been established as an important regulator of inflammation and vascular adhesion. Recently, it has been demonstrated that A(2B)R deficiency enhances neointimal lesion formation after vascular injury. Therefore, we hypothesize that A(2B)R agonism protects against injury-induced intimal hyperplasia.
  
  
  RESULTS
  Apolipoprotein E-deficient mice were fed a Western-type diet for 1 week, after which the left common carotid artery was denuded. Mice were treated with the A(2B) receptor agonist BAY60-6583 or vehicle control for 18 days. Interestingly, lumen stenosis as defined by the neointima/lumen ratio was inhibited by treatment with the A(2B) receptor agonist, caused by reduced smooth muscle cell proliferation. Collagen content was significantly increased in the BAY60-6583-treated mice, whereas macrophage content remained unchanged. In vitro, vascular smooth muscle cell proliferation decreased dose dependently whereas collagen content of cultured smooth muscle cells was increased by BAY60-6583.
  
  
  CONCLUSIONS
  Our data show that activation of the adenosine A(2B) receptor protects against vascular injury, while it also enhances plaque stability as indicated by increased collagen content. These outcomes thus point to A(2B) receptor agonism as a new therapeutic approach in the prevention of restenosis.
authors: Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands. i.bot@lacdr.leidenuniv.nl
authors: Ilze
authors: I
authors: Bot
authors: Henk
authors: H
authors: de Vries
authors: Suzanne J A
authors: SJ
authors: Korporaal
authors: Amanda C
authors: AC
authors: Foks
authors: Martine
authors: M
authors: Bot
authors: Jacobus
authors: J
authors: van Veldhoven
authors: Mariëtte N D
authors: MN
authors: Ter Borg
authors: Peter J
authors: PJ
authors: van Santbrink
authors: Theo J C
authors: TJ
authors: van Berkel
authors: Johan
authors: J
authors: Kuiper
authors: Adriaan P
authors: AP
authors: Ijzerman
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D016466:CHO Cells; D002317:Cardiovascular Agents / Q000494:pharmacology*; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017536:Carotid Artery, Common / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004041:Dietary Fats; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058426:Neointima; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D043704:Receptor, Adenosine A2B / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D058908:Adenosine A2 Receptor Agonists; D000631:Aminopyridines; D001057:Apolipoproteins E; C518875:BAY 60-6583; D002317:Cardiovascular Agents; D004041:Dietary Fats; D043704:Receptor, Adenosine A2B; D003094:Collagen