Universität zu Köln

Hytonen, Jarkko ORCID: 0000-0001-9120-7645, Leppanen, Olli, Braesen, Jan Hinrich, Schunck, Wolf-Hagen, Mueller, Dominik, Jung, Friedrich, Mrowietz, Christoph, Jastroch, Martin, von Bergwelt-Baildon, Michael, Kappert, Kai ORCID: 0000-0001-6976-0428, Heuser, Arnd ORCID: 0000-0002-3334-960X, Drenckhahn, Joerg-Detlef, Pieske, Burkert, Thierfelder, Ludwig, Yla-Herttuala, Seppo ORCID: 0000-0001-7593-2708 and Blaschke, Florian (2016). Activation of Peroxisome Proliferator-Activated Receptor- as Novel Therapeutic Strategy to Prevent In-Stent Restenosis and Stent Thrombosis. Arterioscler. Thromb. Vasc. Biol., 36 (8). S. 1534 - 1549. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1524-4636

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Abstract

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 (PPAR) exhibits actions that could favorably influence outcomes after drug-eluting coronary stents placement. Approach and Results Here, we report that PPAR 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 PPAR-depleted VSMCs, we show that the observed effects of PPAR ligand GW0742 on VSMCs and thrombocytes are PPAR receptor dependent. PPAR 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, PPAR ligands not only inhibit inflammatory response and proliferation of VSMCs but also prevent thrombocyte activation and support vessel re-endothelialization. Thus, pharmacological PPAR activation could be a promising novel strategy to improve drug-eluting coronary stents outcomes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hytonen, Jarkko UNSPECIFIED orcid.org/0000-0001-9120-7645 UNSPECIFIED Leppanen, Olli UNSPECIFIED UNSPECIFIED UNSPECIFIED Braesen, Jan Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Schunck, Wolf-Hagen UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Dominik UNSPECIFIED UNSPECIFIED UNSPECIFIED Jung, Friedrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Mrowietz, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Jastroch, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED von Bergwelt-Baildon, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Kappert, Kai UNSPECIFIED orcid.org/0000-0001-6976-0428 UNSPECIFIED Heuser, Arnd UNSPECIFIED orcid.org/0000-0002-3334-960X UNSPECIFIED Drenckhahn, Joerg-Detlef UNSPECIFIED UNSPECIFIED UNSPECIFIED Pieske, Burkert UNSPECIFIED UNSPECIFIED UNSPECIFIED Thierfelder, Ludwig UNSPECIFIED UNSPECIFIED UNSPECIFIED Yla-Herttuala, Seppo UNSPECIFIED orcid.org/0000-0001-7593-2708 UNSPECIFIED Blaschke, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-268659
DOI:	10.1161/ATVBAHA.115.306962
Journal or Publication Title:	Arterioscler. Thromb. Vasc. Biol.
Volume:	36
Number:	8
Page Range:	S. 1534 - 1549
Date:	2016
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	1524-4636
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VASCULAR SMOOTH-MUSCLE; DRUG-ELUTING STENTS; CELL-PROLIFERATION; PPAR-DELTA; HEART-DISEASE; AMP KINASE; GROWTH; PLATELETS; GAMMA; BETA/DELTA Multiple languages Hematology; Peripheral Vascular Disease Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26865