Polydeoxyribonucleotide (PDRN) restores blood flow in an experimental model of peripheral artery occlusive disease

ObjectiveThis 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.MethodsWe 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.ResultsAdministration of PDRN dramatically increased VEGF mRNA throughout the study (day 14: HLI, 7 ± 2.2 n-fold/β-actin; HLI + PDRN, 13.3 ± 3.8 n-fold/β-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 A2A receptor antagonist, abolished the positive effects of PDRN, confirming that PDRN acts through this receptor.ConclusionThese results led us to hypothesize a role for PDRN in treating peripheral artery occlusive diseases.

Clinical RelevanceThe compound polydeoxyribonucleotide (PDRN), acting through the adenosine receptors, which are expressed during ischemia, can stimulate therapeutic angiogenesis during ischemic conditions without any adverse effect. Owing to this peculiar frame of activity, its use is also safe in diabetic patients where an augmented vascular endothelial growth factor production can be disadvantageous, as we have already demonstrated.