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Local Delivery of β‐Aminopropionitrile Improves Arteriovenous Fistula Maturation and Remodeling
Author(s) -
Hernandez Diana Rosa,
Wei Yuntao,
Andreopoulos Fotios,
VazquezPadron Roberto
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1078.2
Subject(s) - plga , lysyl oxidase , medicine , arteriovenous fistula , urology , chemistry , extracellular matrix , biomedical engineering , surgery , in vitro , biochemistry
Arteriovenous fistula (AVF) is the preferred vascular access to provide hemodialysis in patients with end stage renal disease (ESRD). The failure of AVF due to improper remodeling is a serious condition that affects not only its prevalence but also the possibility of achieving long‐term patency. β‐aminopropionitrile (BAPN) is an irreversible inhibitor of lysyl oxidase (LOX), the main enzyme responsible for collagen crosslinking. Herein, we hypothesize that inhibition of LOX by local delivery of BAPN improves biomechanical performance in experimental AVF and prevents excessive crosslinking of collagen and other extracellular matrix proteins. Methods Poly Lactic‐co‐Glycolic Acid (PLGA) is an FDA‐approved biodegradable highly biocompatible polymer frequently used on deliveries systems. The scaffolds were grown by electrospinning PLGA/BAPN (15:1.5) in hexafluoroisopropanol at 20 keV and 13 cm away from the target with a flow of 2 mL/h. In vitro degradation as well as BAPN release profile was studied during 60 days at 37°C. BAPN concentration was assessed with a Triversa NanoMate® electrospray ionization with direct infusion through triple quadrupole LC‐MS. Two groups of Sprague Dawley rats of both sex received local delivery of scaffold containing BAPN (0.27 mg) or vehicle around the venous limb of the newly created AVF. The rat AVF was created by surgically anastomosing the left epigastric vein to the nearby femoral artery. Pressure myograph (110 P; Danish Myo Technology, Aarhus, Denmark) was used for assessment of the AVF mechanical properties. Results In‐vitro release assessment showed that the drug inclusion in the scaffolds affects degradation rate with a maximum difference of 70% at 40 days. LC‐MS showed an excellent sensitivity for the quantification of BAPN with a lower limit of quantification of 30 ng/mL. Both treated and control AVF increased its size more than double that of the contralateral epigastric vein (p<0.05). However, local delivery of BAPN increased lumen volume in treated AVF with respect to control vessels (p=0.0078), Figure 1. Conclusion Our results demonstrate that inhibition of collagen cross‐linking by BAPN significantly improved vascular compliance and biomechanical properties of AVF. Support or Funding Information This research it is support as a Research Supplements to Promote Diversity in Health under parent award R01DK098511.