title: Effects of recombinant human type I pancreatic elastase on human atherosclerotic arteries.
abstract: BACKGROUND
  At physiologic pressures, elastic fibers constrain artery diameter. Local treatment of atherosclerotic arteries with PRT-201, a recombinant type I elastase, could result in fragmentation and removal of elastin fibers and increased vessel diameter.
  
  
  OBJECTIVE
  To investigate the use of PRT-201 as a treatment for human atherosclerotic arteries.
  
  
  RESULTS
  Arteries were harvested from donor legs amputated due to severe peripheral artery disease or from recently deceased persons who donated their bodies to science. Three- to four-centimeter artery segments were studied on a perfusion myograph to obtain baseline diameter data. After treatment with PRT-201 3.6 mg/mL or saline for 30 minutes myography was repeated. PRT-201 treatment resulted in an increase in vessel diameter across a range of transmural pressures. Average anterior tibial artery diameter increased by 0.78 ± 0.21 mm (27% ± 12%), whereas average posterior tibial artery diameter increased by 0.58 ± 0.30 mm (21% ± 11%), both P < 0.001. Elastin content as measured by desmosine radioimmunoassay was reduced by approximately 50%, P < 0.001.
  
  
  CONCLUSIONS
  The results suggest that PRT-201 treatment of atherosclerotic peripheral arteries in patients could increase artery diameter, and thus luminal area, possibly alleviating some of the symptoms of peripheral artery disease.
authors.affiliation: *Research and Development, Proteon Therapeutics, Inc, Waltham, MA; †Biopta Ltd, Glasgow, United Kingdom; and ‡University of Texas at Tyler, Tyler, TX.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Burke
authors.forename: Karen
authors.initials: K
authors.lastname: Macdonald
authors.forename: Emma
authors.initials: E
authors.lastname: Moss
authors.forename: David
authors.initials: D
authors.lastname: Bunton
authors.forename: Barry
authors.initials: B
authors.lastname: Starcher
authors.forename: Marco D
authors.initials: MD
authors.lastname: Wong
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: Bland
authors.forename: F Nicholas
authors.initials: FN
authors.lastname: Franano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology; D002352:Carrier Proteins / Q000494:pharmacology*; D004547:Elastic Tissue / Q000378:metabolism*; D004549:Elastin / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009213:Myography; D010196:Pancreatic Elastase; D058729:Peripheral Arterial Disease / Q000188:drug therapy* / Q000473:pathology; D010865:Pilot Projects; D011994:Recombinant Proteins; D016909:Tibial Arteries / Q000187:drug effects / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D011994:Recombinant Proteins; D004549:Elastin; D010196:Pancreatic Elastase; C017130:cholesterol-binding protein