PuSH - Publication Server of Helmholtz Zentrum München

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)
Publ. Version/Full Text DOI PMC
Free by publisher
Open Access Green as soon as Postprint is submitted to ZB.
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.
Altmetric
Additional Metrics?
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 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
Quellenangaben Volume: 36, Issue: 8, Pages: 1534-1548 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Publishing Place Philadelphia
Non-patent literature Publications
Reviewing status Peer reviewed