Polydeoxyribonucleotide (PDRN) restores blood flow in an experimental model of peripheral artery occlusive disease (Publication with Expression of Concern. See vol. 76, pg. 613, 2022)

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-l-propargilxanthine (DMPX), a selective adenosine A(2A) receptor antagonist, abolished the positive effects of PDRN, confirming that PDRN acts through this receptor. Conclusion: These results led us to hypothesize a role for PDRN in treating peripheral artery occlusive diseases. (J Vasc Surg 2008;48:1292-1300.)