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Activation of Perox...
Activation of Peroxisome Proliferator-Activated Receptor-δ as Novel Therapeutic Strategy to Prevent In-Stent Restenosis and Stent Thrombosis
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- Hytönen, Jarkko (författare)
- Univ Eastern Finland, Dept Mol Med, AI Virtanen Inst, Kuopio, Finland.
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- Leppänen, Olli (författare)
- Uppsala universitet,Centrum för klinisk forskning, Gävleborg
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- Braesen, Jan Hinrich (författare)
- Univ Clin Schleswig Holstein, Inst Pathol, Campus Kiel, Kiel, Germany.
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- Schunck, Wolf-Hagen (författare)
- Max Delbruck Ctr Mol Med, Berlin, Germany.
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- Mueller, Dominik (författare)
- Max Delbruck Ctr Mol Med, Berlin, Germany.
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- Jung, Friedrich (författare)
- Helmholtz Zentrum Geesthacht, Inst Biomat Sci, Teltow, Germany.;Helmholtz Zentrum Geesthacht, Berlin Brandenburg Ctr Regenerat Therapies BCRT, Teltow, Germany.
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- Mrowietz, Christoph (författare)
- Helmholtz Zentrum Geesthacht, Inst Biomat Sci, Teltow, Germany.;Helmholtz Zentrum Geesthacht, Berlin Brandenburg Ctr Regenerat Therapies BCRT, Teltow, Germany.
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- Jastroch, Martin (författare)
- Helmholtz Zentrum Muenchen, Inst Diabet & Obes, German Res Ctr Environm Hlth, Munich, Germany.
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- von Bergwelt-Baildon, Michael (författare)
- Univ Hosp Cologne, Cologne Intervent Immunol, Cologne, Germany.
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- Kappert, Kai (författare)
- Charite, CCR, Inst Lab Med Clin Chem & Pathobiochem, Berlin, Germany.
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- Heuser, Arnd (författare)
- Max Delbruck Ctr Mol Med, Berlin, Germany.
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- Drenckhahn, Jörg-Detlef (författare)
- Max Delbruck Ctr Mol Med, Berlin, Germany.
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- Pieske, Burkert (författare)
- Charite, Dept Cardiol, Berlin, Germany.
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- Thierfelder, Ludwig (författare)
- Max Delbruck Ctr Mol Med, Berlin, Germany.
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- Ylä-Herttuala, Seppo (författare)
- Univ Eastern Finland, Dept Mol Med, AI Virtanen Inst, Kuopio, Finland.
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- Blaschke, Florian (författare)
- Max Delbruck Ctr Mol Med, Berlin, Germany.;Charite, Dept Cardiol, Berlin, Germany.
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Univ Eastern Finland, Dept Mol Med, AI Virtanen Inst, Kuopio, Finland Centrum för klinisk forskning, Gävleborg (creator_code:org_t)
- 2016
- 2016
- Engelska.
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 36:8, s. 1534-1548
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- blood platelets
- coronary in-stent restenosis
- endothelial cells
- peroxisome proliferator-activated receptors
- vascular smooth muscle cells
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Hytönen, Jarkko
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Leppänen, Olli
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Braesen, Jan Hin ...
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Schunck, Wolf-Ha ...
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Mueller, Dominik
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Jung, Friedrich
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Mrowietz, Christ ...
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Jastroch, Martin
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von Bergwelt-Bai ...
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Kappert, Kai
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Heuser, Arnd
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Drenckhahn, Jörg ...
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Pieske, Burkert
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Thierfelder, Lud ...
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Ylä-Herttuala, S ...
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Blaschke, Floria ...
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