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Grant support

This study was supported by research grants from Kowa Company, Ltd, Nagoya, Japan, to Masanori Aikawa and Farouc A. Jaffer, the National Institutes of Health (R01HL126901 and R01HL149302 to Masanori Aikawa; R01HL122388, R01HL137913, and R01HL150538 to Farouc A. Jaffer; K08HL130465 to Eric A. Osborn; R01HL136431 and R01HL147095 to Elena Aikawa; and R01HL080472 to Peter Libby), American Heart Association (18CSA34080399 to Peter Libby), and the RRM Charitable Fund to Peter Libby. The near--infrared fluorescence--optical coherence tomography system was developed in part under R01HL093717 to Guillermo J. Tearney. Kowa Company, Ltd, Nagoya, Japan, provided partial research funding support for this study but was not involved in the study design or data analysis.

Impact on the Sustainable Development Goals (SDGs)

Analysis of institutional authors

Matamalas, JoanAuthor

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February 9, 2025
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Highly Selective PPARα (Peroxisome Proliferator-Activated Receptor α) Agonist Pemafibrate Inhibits Stent Inflammation and Restenosis Assessed by Multimodality Molecular-Microstructural Imaging

Publicated to:Journal Of The American Heart Association. 10 (20): e020834- - 2021-10-19 10(20), DOI: 10.1161/jaha.121.020834

Authors: Iwata, Hiroshi; Osborn, Eric A; Ughi, Giovanni J; Murakami, Kentaro; Goettsch, Claudia; Hutcheson, Joshua D; Mauskapf, Adam; Mattson, Peter C; Libby, Peter; Singh, Sasha A; Matamalas, Joan; Aikawa, Elena; Tearney, Guillermo J; Aikawa, Masanori; Jaffer, Farouc A

Affiliations

Harvard Med Sch, Beth Israel Deaconess Med Ctr, Cardiol Div, Boston, MA 02115 USA - Author
Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA - Author
Harvard Med Sch, Brigham & Womens Hosp, Ctr Excellence Vasc Biol, Cardiovasc Div, Boston, MA 02115 USA - Author
Harvard Med Sch, Brigham & Womens Hosp, Ctr Interdisciplinary Cardiovasc Sci, Cardiovasc Div, Boston, MA 02115 USA - Author
Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Cardiol Div, Boston, MA 02115 USA - Author
Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA - Author
Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02115 USA - Author
IM Sechenov First Moscow State Med Univ, Dept Human Pathol, Minist Hlth, Moscow, Russia - Author
Juntendo Univ, Grad Sch Med, Dept Cardiovasc Biol & Med, Tokyo, Japan - Author
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Abstract

BACKGROUND New pharmacological approaches are needed to prevent stent restenosis. This study tested the hypothesis that pemafibrate, a novel clinical selective PPAR alpha (peroxisome proliferator-activated receptor alpha) 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 x 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-alpha (tumor necrosis factor-alpha) and MMP-9 (matrix metalloproteinase 9) and enhanced the smooth muscle differentiation markers calponin and smoothelin. In vitro assays indicated that the STAT3 (signal transducer and activator of transcription 3)-myocardin axes mediated the inhibitory effects of pemafibrate on smooth muscle cell proliferation. CONCLUSIONS Pemafibrate reduces preclinical coronary stent inflammation and neointimal hyperplasia following bare metal stent deployment. These results motivate further trials evaluating pemafibrate as a new strategy to prevent clinical stent restenosis.

Keywords

(r)-2-(3-((benzoxazol-2-yl-d4 (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acidAnimalsAtherosclerosiBare-metalBenzoxazolesButyratesConstriction, pathologicCoronary angioplastyCoronary artery diseaseCysteine proteaseDouble-blindGood health and well-beingHyperplasiaInflammationModulator spparm-alphaMolecular imagingNeointimaOptical coherence tomographyPaclitaxel-eluting stentsPemafibratePpar alphaRestenosisSmooth-muscle-cellsSpparm alpha (selective peroxisome proliferator-activated receptor alpha modulator alphaSpparmα (selective peroxisome proliferator-activated receptor alpha modulator alpha)Spparmα (selective peroxisome proliferator‐activated receptor alpha modulator alpha)StentsSwineVascular inflammation

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of The American Heart Association due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Cardiology and Cardiovascular Medicine. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 5.85, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-19, the following number of citations:

  • WoS: 8
  • Scopus: 9
  • Europe PMC: 6
  • Google Scholar: 9
  • Open Alex: 9

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-19:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 14.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 13 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 4.6.
  • The number of mentions on the social network Facebook: 1 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 7 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
Continuing with the social impact of the work, it is important to emphasize that, due to its content, it can be assigned to the area of interest of ODS 3 - Ensure healthy lives and promote well-being for all at all ages, with a probability of 62% according to the mBERT algorithm developed by Aurora University.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Israel; Japan; Russia; United States of America.