Use of Oral Anticoagulation and Diabetes Do Not Inhibit the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes

Patients suffering from tissue ischemia, who would greatly benefit from angiogenesis-promoting therapies such as hypoxia preconditioned blood-derived secretomes commonly receive oral anticoagulation (OA) and/or have diabetes mellitus (DM). In this study, we investigated the effect of OA administrati...

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Main Authors: Philipp Moog, Maryna Jensch, Jessica Hughes, Burak Salgin, Ulf Dornseifer, Hans-Günther Machens, Arndt F. Schilling, Ektoras Hadjipanayi
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/8/8/283
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author Philipp Moog
Maryna Jensch
Jessica Hughes
Burak Salgin
Ulf Dornseifer
Hans-Günther Machens
Arndt F. Schilling
Ektoras Hadjipanayi
author_facet Philipp Moog
Maryna Jensch
Jessica Hughes
Burak Salgin
Ulf Dornseifer
Hans-Günther Machens
Arndt F. Schilling
Ektoras Hadjipanayi
author_sort Philipp Moog
collection DOAJ
description Patients suffering from tissue ischemia, who would greatly benefit from angiogenesis-promoting therapies such as hypoxia preconditioned blood-derived secretomes commonly receive oral anticoagulation (OA) and/or have diabetes mellitus (DM). In this study, we investigated the effect of OA administration on the in vitro angiogenic potential of hypoxia preconditioned plasma (HPP) and serum (HPS), prepared from nondiabetic/diabetic subjects who did not receive OA (<i>n</i> = 5) or were treated with acetylsalicylic acid (ASA, <i>n</i> = 8), ASA + clopidogrel (<i>n</i> = 10), or nonvitamin K antagonist oral anticoagulants (<i>n</i> = 7) for longer than six months. The effect of DM was differentially assessed by comparing HPP/HPS obtained from nondiabetic (<i>n</i> = 8) and diabetic (<i>n</i> = 16) subjects who had not received OA in the past six months. The concentration of key proangiogenic (vascular endothelial growth factor or VEGF) and antiangiogenic (thrombospondin-1 or TSP-1 and platelet factor-4 or PF-4) protein factors in HPP/HPS was analyzed via ELISA, while their ability to induce microvessel formations was examined in endothelial cell cultures. We found that OA use significantly reduced VEGF levels in HPP, but not HPS, compared to non-OA controls. While HPP and HPS TSP-1 levels remained largely unchanged as a result of OA usage, HPS PF-4 levels were significantly reduced in samples obtained from OA-treated subjects. Neither OA administration nor DM appeared to significantly reduce the ability of HPP or HPS to induce microvessel formations in vitro. These findings indicate that OA administration does not limit the angiogenic potential of hypoxia preconditioned blood-derived secretomes, and therefore, it does not prohibit the application of these therapies for supporting tissue vascularization and wound healing in healthy or diabetic subjects.
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spelling doaj.art-d9261d2e3b534856af720c59e72a1f562023-11-20T09:49:21ZengMDPI AGBiomedicines2227-90592020-08-018828310.3390/biomedicines8080283Use of Oral Anticoagulation and Diabetes Do Not Inhibit the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived SecretomesPhilipp Moog0Maryna Jensch1Jessica Hughes2Burak Salgin3Ulf Dornseifer4Hans-Günther Machens5Arndt F. Schilling6Ektoras Hadjipanayi7Experimental Plastic Surgery, Clinic for Plastic, Reconstructive and Hand Surgery, Klinikum Rechts der Isar, Technische Universität München, D-81675 Munich, GermanyExperimental Plastic Surgery, Clinic for Plastic, Reconstructive and Hand Surgery, Klinikum Rechts der Isar, Technische Universität München, D-81675 Munich, GermanyExperimental Plastic Surgery, Clinic for Plastic, Reconstructive and Hand Surgery, Klinikum Rechts der Isar, Technische Universität München, D-81675 Munich, GermanyCentre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UKExperimental Plastic Surgery, Clinic for Plastic, Reconstructive and Hand Surgery, Klinikum Rechts der Isar, Technische Universität München, D-81675 Munich, GermanyExperimental Plastic Surgery, Clinic for Plastic, Reconstructive and Hand Surgery, Klinikum Rechts der Isar, Technische Universität München, D-81675 Munich, GermanyDepartment of Trauma Surgery, Orthopedics and Plastic Surgery, Universitätsmedizin Göttingen, D-37075 Göttingen, GermanyExperimental Plastic Surgery, Clinic for Plastic, Reconstructive and Hand Surgery, Klinikum Rechts der Isar, Technische Universität München, D-81675 Munich, GermanyPatients suffering from tissue ischemia, who would greatly benefit from angiogenesis-promoting therapies such as hypoxia preconditioned blood-derived secretomes commonly receive oral anticoagulation (OA) and/or have diabetes mellitus (DM). In this study, we investigated the effect of OA administration on the in vitro angiogenic potential of hypoxia preconditioned plasma (HPP) and serum (HPS), prepared from nondiabetic/diabetic subjects who did not receive OA (<i>n</i> = 5) or were treated with acetylsalicylic acid (ASA, <i>n</i> = 8), ASA + clopidogrel (<i>n</i> = 10), or nonvitamin K antagonist oral anticoagulants (<i>n</i> = 7) for longer than six months. The effect of DM was differentially assessed by comparing HPP/HPS obtained from nondiabetic (<i>n</i> = 8) and diabetic (<i>n</i> = 16) subjects who had not received OA in the past six months. The concentration of key proangiogenic (vascular endothelial growth factor or VEGF) and antiangiogenic (thrombospondin-1 or TSP-1 and platelet factor-4 or PF-4) protein factors in HPP/HPS was analyzed via ELISA, while their ability to induce microvessel formations was examined in endothelial cell cultures. We found that OA use significantly reduced VEGF levels in HPP, but not HPS, compared to non-OA controls. While HPP and HPS TSP-1 levels remained largely unchanged as a result of OA usage, HPS PF-4 levels were significantly reduced in samples obtained from OA-treated subjects. Neither OA administration nor DM appeared to significantly reduce the ability of HPP or HPS to induce microvessel formations in vitro. These findings indicate that OA administration does not limit the angiogenic potential of hypoxia preconditioned blood-derived secretomes, and therefore, it does not prohibit the application of these therapies for supporting tissue vascularization and wound healing in healthy or diabetic subjects.https://www.mdpi.com/2227-9059/8/8/283acetylsalicylic acidangiogenesisblood-derived therapyCOX-1clopidogreldrug anticoagulation
spellingShingle Philipp Moog
Maryna Jensch
Jessica Hughes
Burak Salgin
Ulf Dornseifer
Hans-Günther Machens
Arndt F. Schilling
Ektoras Hadjipanayi
Use of Oral Anticoagulation and Diabetes Do Not Inhibit the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes
Biomedicines
acetylsalicylic acid
angiogenesis
blood-derived therapy
COX-1
clopidogrel
drug anticoagulation
title Use of Oral Anticoagulation and Diabetes Do Not Inhibit the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes
title_full Use of Oral Anticoagulation and Diabetes Do Not Inhibit the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes
title_fullStr Use of Oral Anticoagulation and Diabetes Do Not Inhibit the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes
title_full_unstemmed Use of Oral Anticoagulation and Diabetes Do Not Inhibit the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes
title_short Use of Oral Anticoagulation and Diabetes Do Not Inhibit the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes
title_sort use of oral anticoagulation and diabetes do not inhibit the angiogenic potential of hypoxia preconditioned blood derived secretomes
topic acetylsalicylic acid
angiogenesis
blood-derived therapy
COX-1
clopidogrel
drug anticoagulation
url https://www.mdpi.com/2227-9059/8/8/283
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