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At physiologic pressures, elastin fibers constrain artery diameter. Removing elastin fibers from an atherosclerotic artery could result in larger artery lumen diameter and greater blood flow. The purpose of this study was to investigate the use of PRT-201 as a treatment for peripheral artery disease (PAD).
Anterior and posterior tibial arteries were obtained within 24 hrs of death from persons who donated their bodies to science. The arteries were visually atherosclerotic. 3-4 cm long segments of artery were mounted onto the perfusion myograph and bathed in Krebs solution at 37C gassed with a mix of 95% O2/ 5% CO2. Transmural pressures were increased from 10 to 80 mmHg while diameter was continuously recorded to create a compliance curve. Then PRT-201 was applied at a concentration of 3.6 mg/mL for 30 min and the compliance curve was repeated. The artery was analyzed for elastin content by desmosine radioimmunoassay (RIA). Desmosine is a protein cross-link unique to elastin.
6 donors provided 10 tibial arteries. The figure displays the compliance curves for the tibial arteries pre- and post-PRT-201. Average anterior tibial artery diameter increased by 0.78 ± 0.21 mm (27 ± 12%) and average posterior tibial artery diameter increased by 0.58 ± 0.30 mm (21 ± 11%), all p<0.001, following PRT-201 treatment. PRT-201 reduced elastin content measured by desmosine RIA by approximately 50%.
PRT-201 treatment removed elastin from atherosclerotic tibial arteries and altered artery compliance so as to increase artery diameter.
- 2012 American College of Cardiology Foundation