Novel Injury Site Targeted Fusion Protein Comprising Annexin V and Kunitz Inhibitor Domains Ameliorates Ischemia-Reperfusion Injury and Promotes Survival of Ischemic Rat Abdominal Skin Flaps
| Autor: | Chih-Jen Wen, Fu-Chan Wei, Victor Bong-Hang Shyu, Samuel Achilefu, Tze-Chein Wun, Hui-Yun Cheng, Rui Tang, Chung En Hsu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
Pathology medicine.medical_specialty Recombinant Fusion Proteins Ischemia 030204 cardiovascular system & hematology Pharmacology Surgical Flaps Article 03 medical and health sciences 0302 clinical medicine Injury Site Aprotinin Annexin Antithrombotic Abdomen medicine Animals Annexin A5 business.industry Graft Occlusion Vascular Hemodynamics medicine.disease Fusion protein Recombinant Proteins Rats Disease Models Animal Rats Inbred Lew 030220 oncology & carcinogenesis Reperfusion Injury Surgery business Reperfusion injury medicine.drug |
| Zdroj: | Ann Plast Surg |
| ISSN: | 1536-3708 |
| Popis: | Appropriate antithrombotic therapy is critical for successful outcomes in reconstructive microsurgical procedures involving free tissue transfer. The annexin V-6L15 (ANV-6L15) fusion protein was developed as a targeted antithrombotic reagent. Annexin V specifically binds to exposed phosphatidylserine on apoptotic or injured cells, and prevents coagulation and cell adhesion, whereas 6L15 inhibits tissue factor-VIIa pathway within the coagulation cascade. The treatment efficacy of ANV-6L15 on rat island muscle and pedicled abdominal fasciocutaneous flaps following ischemic injury and ischemia-reperfusion injury (IRI) was evaluated. MATERIALS AND METHODS: The effects of ANV-6L15 on survival of rat abdominal fasciocutaneous flaps subjected to 10 hours of critical ischemia were assessed on day 5. Near-IR imaging was applied to evaluate the distribution of ANV-6L15 and flap perfusion. The rat cremaster muscle island flap was used to evaluate the effect of ANV-6L15 on IRI-induced leukocyte-endothelial interactions via intravital microscopy. 2,3,5 triphenyl-tetrazolium chloride assay was used to determine the ratio between live-versus-dead tissue. RESULTS: ANV-6L15 significantly increased the ratio of viable tissue (68.5 ± 9.79% vs 84.8 ± 5.14%, P < 0.05), and promoted survival of rat pedicled abdominal flaps (59.3 ± 6.86 vs. 47.0 ± 8.67, P < 0.05). Intravital microscopy demonstrated a significant decrease in the number of adhesive leukocytes (1.8 ± 1.64 vs. 10.0 ± 6.32, P < 0.05), and the percentage change of functional capillaries (16.4 ± 15.1 vs. 47.3 ± 18.3, P < 0.05) in ANV-6L15-treatment group. CONCLUSIONS: ANV-6L15 promoted survival of ischemic rat cremaster muscle and abdominal fasciocutaneous flaps and ameliorated leukocyte-related IRI. Future evaluation of potential clinical application of ANV-6L15 is warranted as a flap treatment adjunct. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|