Recombinant Human Elastase Treatment of Cephalic Veins.
BACKGROUND
Vessel injury at the time of Arteriovenous Fistula (AVF) creation may lead to neointimal hyperplasia that impairs AVF maturation. Vonapanitase, a recombinant human chymotrypsin-like elastase family member 1, is an investigational drug under development to improve AVF maturation and patency. The current studies were designed to document vonapanitase effects in human cephalic veins that are used in AVF creation.


METHODS
Human cephalic veins were mounted on a perfusion myograph. Vonapanitase 1.2, 4, 13.2, and 40 μg/ml or saline was applied drop wise on the vein followed by saline rinse. Vein segments were cut into rings for elastin content determination by desmosine radioimmunoassay and histology. Fluorescently-labelled vonapanitase was applied to veins and adventitial imaging was performed using laser scanning confocal microscopy.In vivotime course experiments were performed by treating rabbit jugular veins and harvesting 1 h and 4 h after vonapanitase treatment.
Vonapanitase reduced desmosine content in a dose-related manner. Histology also confirmed a dose-related reduction in elastic fiber staining. Fluorescently-labelled vonapanitase persistently localized to elastic fibers in the vein adventitia.In vivoexperiments showed a reduction in desmosine content in jugular veins from 1 h to 4 h following treatment. These data suggest that vonapanitase targets elastin in elastic fibers in a dose related manner and that elastase remains in the vessel wall and has catalytic activity for at least 1 h.
Research and Development, Proteon Therapeutics, Inc. Waltham, Massachusetts, USA.
Marco D
MD
Wong
Biopta Ltd., Glasgow, Scotland, UK.
Karen
K
Bingham
Biopta Ltd., Glasgow, Scotland, UK.
Emma
E
Moss
University of Kansas Medical Center, Kansas City, USA.
J Donald
JD
Warn
Research and Development, Proteon Therapeutics, Inc. Waltham, Massachusetts, USA.
Igor
I
Smirnov
Research and Development, Proteon Therapeutics, Inc. Waltham, Massachusetts, USA.
Kimberly S
KS
Bland
University of Texas at Tyler, Texas, USA.
Barry
B
Starcher
Research and Development, Proteon Therapeutics, Inc. Waltham, Massachusetts, USA.
F Nicholas
FN
Franano
Research and Development, Proteon Therapeutics, Inc. Waltham, Massachusetts, USA.
Steven K
SK
Burke
AVF; Arteriovenous fistula; CELA1; Chymotrypsin-like elastase family member 1; Elastase; Elastin; Hemodialysis access; PRT-201; Vonapanitase