Micro-RNA-Regulated Proangiogenic Signaling in Arteriovenous Loops in Patients with Combined Vascular and Soft-Tissue Reconstructions: Revisiting the Nutrient Flap Concept
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Micro-RNA-Regulated Proangiogenic Signaling in Arteriovenous Loops in Patients with Combined Vascular and Soft-Tissue Reconstructions : Revisiting the Nutrient Flap Concept. / Henn, Dominic; Abu-Halima, Masood; Falkner, Florian; Wermke, Dominik; Meme, Lilian G; Kühner, Clemens; Keller, Andreas; Kneser, Ulrich; Meese, Eckart; Schmidt, Volker J.
I: Plastic and Reconstructive Surgery, Bind 142, Nr. 4, 2018, s. 489e-502e.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Micro-RNA-Regulated Proangiogenic Signaling in Arteriovenous Loops in Patients with Combined Vascular and Soft-Tissue Reconstructions
T2 - Revisiting the Nutrient Flap Concept
AU - Henn, Dominic
AU - Abu-Halima, Masood
AU - Falkner, Florian
AU - Wermke, Dominik
AU - Meme, Lilian G
AU - Kühner, Clemens
AU - Keller, Andreas
AU - Kneser, Ulrich
AU - Meese, Eckart
AU - Schmidt, Volker J
PY - 2018
Y1 - 2018
N2 - BACKGROUND: The placement of arteriovenous loops can enable microvascular anastomoses of free flaps when recipient vessels are scarce. In animal models, elevated fluid shear stress in arteriovenous loops promotes neoangiogenesis. Anecdotal reports in patients indicate that vein grafts used in free flap reconstructions of ischemic lower extremities are able to induce capillary formation. However, flow-stimulated angiogenesis has never been systematically investigated in humans, and it is unclear whether shear stress alters proangiogenic signaling pathways within the vascular wall of human arteriovenous loops.METHODS: Eight patients with lower extremity soft-tissue defects underwent two-stage reconstruction with arteriovenous loop placement, and free flap anastomoses to the loops 10 to 14 days later. Micro-RNA (miRNA) and gene expression profiles were determined in tissue samples harvested from vein grafts of arteriovenous loops by microarray analysis and quantitative real-time polymerase chain reaction. Samples from untreated veins served as controls.RESULTS: A strong deregulation of miRNA and gene expression was detected in arteriovenous loops, showing an overexpression of angiopoietic cytokines, oxygenation-associated genes, vascular growth factors, and connexin-43. The authors discovered inverse correlations along with validated and bioinformatically predicted interactions between angiogenesis-regulating genes and miRNAs in arteriovenous loops.CONCLUSIONS: The authors' findings demonstrate that elevated shear stress triggers proangiogenic signaling pathways in human venous tissue, indicating that arteriovenous loops may have the ability to induce neoangiogenesis in humans. The authors' data corroborate the nutrient flap hypothesis and provide a molecular background for arteriovenous loop-based tissue engineering with potential clinical applications for soft-tissue defect reconstruction.
AB - BACKGROUND: The placement of arteriovenous loops can enable microvascular anastomoses of free flaps when recipient vessels are scarce. In animal models, elevated fluid shear stress in arteriovenous loops promotes neoangiogenesis. Anecdotal reports in patients indicate that vein grafts used in free flap reconstructions of ischemic lower extremities are able to induce capillary formation. However, flow-stimulated angiogenesis has never been systematically investigated in humans, and it is unclear whether shear stress alters proangiogenic signaling pathways within the vascular wall of human arteriovenous loops.METHODS: Eight patients with lower extremity soft-tissue defects underwent two-stage reconstruction with arteriovenous loop placement, and free flap anastomoses to the loops 10 to 14 days later. Micro-RNA (miRNA) and gene expression profiles were determined in tissue samples harvested from vein grafts of arteriovenous loops by microarray analysis and quantitative real-time polymerase chain reaction. Samples from untreated veins served as controls.RESULTS: A strong deregulation of miRNA and gene expression was detected in arteriovenous loops, showing an overexpression of angiopoietic cytokines, oxygenation-associated genes, vascular growth factors, and connexin-43. The authors discovered inverse correlations along with validated and bioinformatically predicted interactions between angiogenesis-regulating genes and miRNAs in arteriovenous loops.CONCLUSIONS: The authors' findings demonstrate that elevated shear stress triggers proangiogenic signaling pathways in human venous tissue, indicating that arteriovenous loops may have the ability to induce neoangiogenesis in humans. The authors' data corroborate the nutrient flap hypothesis and provide a molecular background for arteriovenous loop-based tissue engineering with potential clinical applications for soft-tissue defect reconstruction.
KW - Arteriovenous Shunt, Surgical/methods
KW - Free Tissue Flaps/blood supply
KW - Gene Expression Profiling
KW - Humans
KW - Intercellular Signaling Peptides and Proteins/metabolism
KW - Lower Extremity/surgery
KW - MicroRNAs/metabolism
KW - Microarray Analysis
KW - Microsurgery
KW - Real-Time Polymerase Chain Reaction
KW - Plastic Surgery Procedures/methods
KW - Soft Tissue Injuries/metabolism
KW - Veins/metabolism
U2 - 10.1097/PRS.0000000000004750
DO - 10.1097/PRS.0000000000004750
M3 - Journal article
C2 - 29979372
VL - 142
SP - 489e-502e
JO - Plastic and Reconstructive Surgery
JF - Plastic and Reconstructive Surgery
SN - 0032-1052
IS - 4
ER -
ID: 329566100