title: Lysine acetyltransferase PCAF is a key regulator of arteriogenesis.
abstract: OBJECTIVE
  Therapeutic arteriogenesis, that is, expansive remodeling of preexisting collaterals, using single-action factor therapies has not been as successful as anticipated. Modulation of factors that act as a master switch for relevant gene programs may prove more effective. Transcriptional coactivator p300-CBP-associated factor (PCAF) has histone acetylating activity and promotes transcription of multiple inflammatory genes. Because arteriogenesis is an inflammation-driven process, we hypothesized that PCAF acts as multifactorial regulator of arteriogenesis.
  
  
  RESULTS
  After induction of hindlimb ischemia, blood flow recovery was impaired in both PCAF(-/-) mice and healthy wild-type mice treated with the pharmacological PCAF inhibitor Garcinol, demonstrating an important role for PCAF in arteriogenesis. PCAF deficiency reduced the in vitro inflammatory response in leukocytes and vascular cells involved in arteriogenesis. In vivo gene expression profiling revealed that PCAF deficiency results in differential expression of 3505 genes during arteriogenesis and, more specifically, in impaired induction of multiple proinflammatory genes. Additionally, recruitment from the bone marrow of inflammatory cells, in particular proinflammatory Ly6C(hi) monocytes, was severely impaired in PCAF(-/-) mice.
  
  
  CONCLUSIONS
  These findings indicate that PCAF acts as master switch in the inflammatory processes required for effective arteriogenesis.
authors.affiliation: Department of Surgery, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Antonius J N M
authors.initials: AJ
authors.lastname: Bastiaansen
authors.forename: Mark M
authors.initials: MM
authors.lastname: Ewing
authors.forename: Hetty C
authors.initials: HC
authors.lastname: de Boer
authors.forename: Tineke C
authors.initials: TC
authors.lastname: van der Pouw Kraan
authors.forename: Margreet R
authors.initials: MR
authors.lastname: de Vries
authors.forename: Erna A B
authors.initials: EA
authors.lastname: Peters
authors.forename: Sabine M J
authors.initials: SM
authors.lastname: Welten
authors.forename: Ramon
authors.initials: R
authors.lastname: Arens
authors.forename: Scott M
authors.initials: SM
authors.lastname: Moore
authors.forename: James E
authors.initials: JE
authors.lastname: Faber
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.forename: Jaap F
authors.initials: JF
authors.lastname: Hamming
authors.forename: A Yaël
authors.initials: AY
authors.lastname: Nossent
authors.forename: Paul H A
authors.initials: PH
authors.lastname: Quax
mesh_terms: D000107:Acetylation; D000818:Animals; D001167:Arteritis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000276:immunology; D006614:Hindlimb / Q000098:blood supply; D006657:Histones / Q000378:metabolism; D007511:Ischemia / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013729:Terpenes / Q000494:pharmacology; D059467:Transcriptome; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology*; D000099224:p300-CBP-Associated Factor
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D013729:Terpenes; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C054597:garcinol
keywords: inflammation; monocytes; p300-CBP–associated factor; peripheral arterial disease