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Hytönen, J.* ; Leppaenen, O.* ; Braesen, J.H.* ; Schunck, W.H.* ; Müller, D.* ; Jung, F.* ; Mrowietz, C.* ; Jastroch, M. ; von Bergwelt-Baildon, M.* ; Kappert, K.* ; Heuser, A.* ; Drenckhahn, J.D.* ; Pieske, B.* ; Thierfelder, L.* ; Yla-Herttuala, S.* ; Blaschke, F.*

Activation of peroxisome proliferator-activated receptor-δ as novel therapeutic strategy to prevent in-stent restenosis and stent thrombosis.

Arterioscler. Thromb. Vasc. Biol. 36, 1534-1548 (2016)
Verlagsversion DOI PMC
Free by publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
OBJECTIVE: Drug-eluting coronary stents reduce restenosis rate and late lumen loss compared with bare-metal stents; however, drug-eluting coronary stents may delay vascular healing and increase late stent thrombosis. The peroxisome proliferator-activated receptor-delta (PPARδ) exhibits actions that could favorably influence outcomes after drug-eluting coronary stents placement. APPROACH AND RESULTS: Here, we report that PPARδ ligand-coated stents strongly reduce the development of neointima and luminal narrowing in a rabbit model of experimental atherosclerosis. Inhibition of inflammatory gene expression and vascular smooth muscle cell (VSMC) proliferation and migration, prevention of thrombocyte activation and aggregation, and proproliferative effects on endothelial cells were identified as key mechanisms for the prevention of restenosis. Using normal and PPARδ-depleted VSMCs, we show that the observed effects of PPARδ ligand GW0742 on VSMCs and thrombocytes are PPARδ receptor dependent. PPARδ ligand treatment induces expression of pyruvate dehydrogenase kinase isozyme 4 and downregulates the glucose transporter 1 in VSMCs, thus impairing the ability of VSMCs to provide the increased energy demands required for growth factor-stimulated proliferation and migration. CONCLUSIONS: In contrast to commonly used drugs for stent coating, PPARδ ligands not only inhibit inflammatory response and proliferation of VSMCs but also prevent thrombocyte activation and support vessel re-endothelialization. Thus, pharmacological PPARδ activation could be a promising novel strategy to improve drug-eluting coronary stents outcomes.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Blood Platelets ; Coronary Restenosis ; Muscle, Smooth, Vascular ; Peroxisome Proliferator-activated Receptors ; Stents; Vascular Smooth-muscle; Drug-eluting Stents; American-heart-association; Ppar-delta; Cell-proliferation; Growth-factor; Platelet-aggregation; Metabolic Syndrome; Skeletal-muscle; Fatty-acids
ISSN (print) / ISBN 1079-5642
e-ISSN 1524-4636
Zeitschrift Arteriosclerosis, Thrombosis, and Vascular Biology
Quellenangaben Band: 36, Heft: 8, Seiten: 1534-1548 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Philadelphia
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)