Polydeoxyribonucleotide (PDRN) restores blood flow in an experimental model of peripheral artery occlusive disease.
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.
Bitto
Alessandra
A
Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Messina, Italy.
Polito
Francesca
F
Altavilla
Domenica
D
Minutoli
Letteria
L
Migliorato
Alba
A
Squadrito
Francesco
F
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
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