title: Propionyl-L-carnitine improves postischemic blood flow recovery and arteriogenetic revascularization and reduces endothelial NADPH-oxidase 4-mediated superoxide production.
abstract: OBJECTIVE
  The beneficial effect of the natural compound propionyl-l-carnitine (PLC) on intermittent claudication in patients with peripheral arterial disease is attributed to its anaplerotic function in ischemic tissues, but inadequate information is available concerning action on the vasculature.
  
  
  RESULTS
  We investigated the effects of PLC in rabbit hind limb collateral vessels after femoral artery excision, mouse dorsal air pouch, chicken chorioallantoic membrane, and vascular cells by angiographic, Doppler flow, and histomorphometrical and biomolecular analyses. PLC injection accelerated hind limb blood flow recovery after 4 days (P<0.05) and increased angiographic quadriceps collateral vascularization after 7 days (P<0.001) Histomorphometry confirmed the increased vascular area (P<0.05), with unchanged intramuscular capillary density. PLC-induced dilatative adaptation, and growth was found associated with increased inducible nitric oxide synthase and reduced arterial vascular endothelial growth factor and intracellular adhesion molecule-1 expression. PLC also increased vascularization in air pouch and chorioallantoic membrane (P<0.05), particularly in large vessels. PLC increased endothelial and human umbilical vascular endothelial cell proliferation and rapidly reduced inducible nitric oxide synthase and NADPH-oxidase 4-mediated reactive oxygen species production in human umbilical vascular endothelial cells; NADPH-oxidase 4 also regulated NF-kappaB-independent intracellular adhesion molecule-1 expression.
  
  
  CONCLUSIONS
  Our results provided strong evidence that PLC improves postischemic flow recovery and revascularization and reduces endothelial NADPH-oxidase-related superoxide production. We recommend that PLC should be included among therapeutic interventions that target endothelial function.
authors.affiliation: Dept. of Biopathology and Image Diagnostics, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Stasi
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Scioli
authors.forename: Gaetano
authors.initials: G
authors.lastname: Arcuri
authors.forename: Giovan Giuseppe
authors.initials: GG
authors.lastname: Mattera
authors.forename: Katia
authors.initials: K
authors.lastname: Lombardo
authors.forename: Marcella
authors.initials: M
authors.lastname: Marcellini
authors.forename: Teresa
authors.initials: T
authors.lastname: Riccioni
authors.forename: Sandro
authors.initials: S
authors.lastname: De Falco
authors.forename: Claudio
authors.initials: C
authors.lastname: Pisano
authors.forename: Luigi Giusto
authors.initials: LG
authors.lastname: Spagnoli
authors.forename: Franco
authors.initials: F
authors.lastname: Borsini
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001808:Blood Vessels / Q000502:physiology*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D003097:Collateral Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007511:Ischemia / Q000503:physiopathology; D051379:Mice; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D042461:Vascular Endothelial Growth Factor A; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; C003223:propionylcarnitine; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; D002331:Carnitine