Effects of recombinant human type I pancreatic elastase on human atherosclerotic arteries

J Cardiovasc Pharmacol. 2014 Dec;64(6):530-5. doi: 10.1097/FJC.0000000000000149.

Abstract

Rationale: 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.

Methods and 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / pathology
  • Carrier Proteins / pharmacology*
  • Elastic Tissue / metabolism*
  • Elastin / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myography
  • Pancreatic Elastase
  • Peripheral Arterial Disease / drug therapy*
  • Peripheral Arterial Disease / pathology
  • Pilot Projects
  • Recombinant Proteins
  • Tibial Arteries / drug effects
  • Tibial Arteries / pathology

Substances

  • Carrier Proteins
  • Recombinant Proteins
  • Elastin
  • Pancreatic Elastase
  • cholesterol-binding protein