Highly Selective PPARα (Peroxisome Proliferator‐Activated Receptor α) Agonist Pemafibrate Inhibits Stent Inflammation and Restenosis Assessed by Multimodality Molecular‐Microstructural Imaging

作者：Hiroshi Iwata, Eric A. Osborn, Giovanni J. Ughi, Kentaro Murakami, Claudia Goettsch, Joshua D. Hutcheson, Adam Mauskapf, Peter C. Mattson, Peter Libby, Sasha A. Singh, Joan T. Matamalas, Elena Aïkawa, Guillermo J. Tearney, Masanori Aikawa, Farouc A. Jaffer · 发表于：Journal of the American Heart Association · 年份：2021 · DOI：10.1161/jaha.121.020834 · 被引用次数：14 · 研究领域：Coronary Interventions and Diagnostics、Antiplatelet Therapy and Cardiovascular Diseases、Cardiac Imaging and Diagnostics

BACKGROUND New pharmacological approaches are needed to prevent stent restenosis. This study tested the hypothesis that pemafibrate, a novel clinical selective PPARα (peroxisome proliferator‐activated receptor α) agonist, suppresses coronary stent‐induced arterial inflammation and neointimal hyperplasia. METHODS AND RESULTS Yorkshire pigs randomly received either oral pemafibrate (30 mg/day; n=6) or control vehicle (n=7) for 7 days, followed by coronary arterial implantation of 3.5 × 12 mm bare metal stents (2–4 per animal; 44 stents total). On day 7, intracoronary molecular‐structural near‐infrared fluorescence and optical coherence tomography imaging was performed to assess the arterial inflammatory response, demonstrating that pemafibrate reduced stent‐induced inflammatory protease activity (near‐infrared fluorescence target‐to‐background ratio: pemafibrate, median [25th‐75th percentile]: 2.8 [2.5–3.3] versus control, 4.1 [3.3–4.3], P =0.02). At day 28, animals underwent repeat near‐infrared fluorescence–optical coherence tomography imaging and were euthanized, and coronary stent tissue molecular and histological analyses. Day 28 optical coherence tomography imaging showed that pemafibrate significantly reduced stent neointima volume (pemafibrate, 43.1 [33.7–54.1] mm 3 versus control, 54.2 [41.2–81.1] mm 3 ; P =0.03). In addition, pemafibrate suppressed day 28 stent‐induced cellular inflammation and neointima expression of the inflammatory mediators TNF‐α (tumor necrosis f...