title: Polydeoxyribonucleotide (PDRN) restores blood flow in an experimental model of peripheral artery occlusive disease.
abstract: OBJECTIVE
  This study investigated whether polydeoxyribonucleotide (PDRN) may be efficacious in the treatment of peripheral artery occlusive diseases, which are a major cause of morbidity in Western countries and still lack standardized treatment.
  
  
  METHODS
  We investigated the effects of PDRN, a mixture of deoxyribonucleotides, in an experimental model of hind limb ischemia (HLI) in rats to stimulate vascular endothelial growth factor (VEGF)-A production and to avoid critical ischemia. The femoral artery was excised to induce HLI. Sham-operated on rats (sham HLI) were used as controls. Animals were treated daily with intraperitoneal PDRN (8 mg/kg) or its vehicle. Animals were euthanized at day 7, 14, and 21 after the evaluation of blood flow by laser Doppler. Dissected muscles were used to measure VEGF-A messenger RNA (mRNA) and protein expression, to evaluate edema, and to assess histologic damage.
  
  
  RESULTS
  Administration of PDRN dramatically increased VEGF mRNA throughout the study (day 14: HLI, 7 +/- 2.2 n-fold/beta-actin; HLI + PDRN, 13.3 +/- 3.8 n-fold/beta-actin; P < .0001) and protein expression (HLI, 11 +/- 3.4 integrated intensity; HLI + PDRN, 16 +/- 3.8 integrated intensity; P < .0001). The compound stimulated revascularization, as confirmed by blood flow restoration (P < .005 vs HLI + vehicle), and blunted the histologic damage and the degree of edema. PDRN did not modify VEGF-A expression and blood flow in sham HLI animals. Furthermore, the concomitant administration of 3,7-dimethyl-1-propargilxanthine (DMPX), a selective adenosine A(2A) receptor antagonist, abolished the positive effects of PDRN, confirming that PDRN acts through this receptor.
  
  
  CONCLUSIONS
  These results led us to hypothesize a role for PDRN in treating peripheral artery occlusive diseases.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Messina, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: Francesca
authors.initials: F
authors.lastname: Polito
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Alba
authors.initials: A
authors.lastname: Migliorato
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
mesh_terms: D058908:Adenosine A2 Receptor Agonists; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology / Q000517:prevention & control; D006614:Hindlimb; D007511:Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D016491:Peripheral Vascular Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043683:Receptors, Adenosine A2 / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D058908:Adenosine A2 Receptor Agonists; D043925:Angiogenesis Inducing Agents; D002317:Cardiovascular Agents; D011089:Polydeoxyribonucleotides; D012333:RNA, Messenger; D043683:Receptors, Adenosine A2; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat