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J Cardiovasc Transl Res. 2021 Jun;14(3):409-415. doi: 10.1007/s12265-020-10066-9. Epub 2020 Sep 01.

Double VEGF/HGF Gene Therapy in Critical Limb Ischemia Complicated by Diabetes Mellitus.

Journal of cardiovascular translational research

Piotr Barć, Maciej Antkiewicz, Barbara Śliwa, Katarzyna Frączkowska, Maciej Guziński, Tomasz Dawiskiba, Małgorzata Małodobra-Mazur, Wojciech Witkiewicz, Diana Kupczyńska, Bartłomiej Strzelec, Dariusz Janczak, Jan Paweł Skóra

Affiliations

  1. Department and Clinic of Vascular, General and Transplantation Surgery, Jan Mikulicz-Radecki Medical University Hospital, Wroclaw Medical University, Wroclaw, Poland.
  2. Department and Clinic of Vascular, General and Transplantation Surgery, Jan Mikulicz-Radecki Medical University Hospital, Wroclaw Medical University, Wroclaw, Poland. [email protected].
  3. Department of Radiology, Jan Mikulicz-Radecki Medical University Hospital, Wroclaw Medical University, Wroclaw, Poland.
  4. Molecular Techniques Unit, Wroclaw Medical University, Wroclaw, Poland.
  5. Regional Specialized Hospital in Wroclaw, Research and Development Center, Wroclaw, Poland.

PMID: 32875492 PMCID: PMC8219552 DOI: 10.1007/s12265-020-10066-9

Abstract

Critical leg ischemia (CLI) complicated by diabetes mellitus (DM), which is a very common and dangerous disease, represents the ultimate stage of peripheral arterial disease. Patients are treated with antiplatelet drugs, statins and limb revascularization, but a significant number of patients are not candidate for revascularization. Literature shows that in such cases, gene therapy could be a perfect therapeutic option. The aim of our study was to evaluate efficacy of double vascular endothelial growth factor/hepatocyte growth factor (VEGF/HGF) gene therapy in patients with CLI complicated by DM. We observed that 90 days after administration, serum level of VEGF and ankle-brachial index increased significantly (p < 0.001) and rest pain decreased significantly compared with the control group (p < 0.002). Moreover considerable improvement in vascularization was observed in computed tomography angiography (P = 0.04). Based on the results of this study, we suggest that the therapy with pIRES/VEGF165/HGF bicistronic plasmid administration is a safe and effective method of treatment of patients with both CLI and DM. Graphical abstract.

Keywords: Critical limb ischemia; Diabetes mellitus; Gene therapy; HGF; VEGF

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