title: cAMP induces adhesion of microvascular smooth muscle cells to fibronectin via an Epac-mediated but PKA-independent mechanism.
abstract: OBJECTIVE
  Vascular smooth muscle cells (VSMCs) play important roles, both in physiologic and pathophysiologic processes. Adhesion of these cells is critical for their proper functioning, especially in resistance-sized vessels. Nonetheless, very little is known about mechanisms regulating adhesion of VSMCs. In particular, the role of cAMP and its downstream effectors, PKA and Epac, remain poorly investigated.
  
  
  METHODS
  Primary cultured cells were isolated from human dermal arterioles and adhesion to fibronectin measured. Adhesion assay was performed in the presence or absence of cAMP elevating agents and activators or inhibitors of PKA or Epac signaling.
  
  
  RESULTS
  cAMP increases adhesion of microvascular smooth muscle cells to fibronectin in concentration and time-dependent fashions. Pretreatment with H89, a PKA inhibitor, did not affect the adhesion, indicating a PKA-independence of the induced adhesion. Selective activation of PKA did not affect adhesion, whereas selective activation of Epac (by 8-pCPT-2'-O-Me-cAMP) increased adhesion. Moreover, expression of a dominant negative mutant of Epac abolished the induced adhesion. cAMP elevation by a physiologic agonist, isoproterenol, mimicked the results obtained with forskolin or 8-pCPT-2'-O-Me-cAMP. Blocking β1 integrins abrogated the induced adhesion.
  
  
  CONCLUSIONS
  The results of this study demonstrate for the first time that cAMP induces adhesion of human microvascular smooth muscle cells to fibronectin via β1 integrins. This adhesion appears to be mediated by Epac, independently if PKA.
authors: Department of Biological and Environmental Sciences, Qatar University, Doha, Qatar. ali.eid@qu.edu.qa
authors: Ali H
authors: AH
authors: Eid
mesh_terms: D001160:Arterioles / Q000166:cytology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004789:Enzyme Activation; D005353:Fibronectins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D005353:Fibronectins; D020662:Guanine Nucleotide Exchange Factors; D019012:Integrin beta1; D007546:Isoquinolines; C116122:RAPGEF3 protein, human; D013449:Sulfonamides; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide