The antiplatelet agent revacept prevents the increase of systemic thromboxane A2 biosynthesis and neointima hyperplasia

Abstract Neointima hyperplasia is a crucial component of restenosis after coronary angioplasty. We have hypothesized that enhanced generation of platelet-derived thromboxane (TX)A2 in response to vascular damage plays a critical role in neointimal hyperplasia and that antiplatelet agents may mitigat...

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Autores principales: Sara Alberti, Qianqian Zhang, Ilaria D’Agostino, Annalisa Bruno, Stefania Tacconelli, Annalisa Contursi, Simone Guarnieri, Melania Dovizio, Lorenza Falcone, Patrizia Ballerini, Götz Münch, Ying Yu, Paola Patrignani
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Publicado: Nature Portfolio 2020
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spelling oai:doaj.org-article:e6a515e9c8494e3e985c043ce7cad9e02021-12-02T15:11:51ZThe antiplatelet agent revacept prevents the increase of systemic thromboxane A2 biosynthesis and neointima hyperplasia10.1038/s41598-020-77934-x2045-2322https://doaj.org/article/e6a515e9c8494e3e985c043ce7cad9e02020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77934-xhttps://doaj.org/toc/2045-2322Abstract Neointima hyperplasia is a crucial component of restenosis after coronary angioplasty. We have hypothesized that enhanced generation of platelet-derived thromboxane (TX)A2 in response to vascular damage plays a critical role in neointimal hyperplasia and that antiplatelet agents may mitigate it. In cocultures of human platelets and coronary artery smooth muscle cells (CASMC), we found that platelets induced morphologic changes and enhanced the migration of CASMC. The exposure of platelets to Aspirin [an inhibitor of cyclooxygenase (COX)-1] reduced the generation of TXA2 and prevented the morphological and functional changes induced by platelets in CASMC. Platelet-derived TXA2 induced COX-2 and enhanced prostaglandin (PG)E2 biosynthesis in CASMC, a known mechanism promoting neointimal hyperplasia. COX-2 induction was prevented by different antiplatelet agents, i.e., Aspirin, the TP antagonist SQ29,548, or Revacept (a dimeric soluble GPVI-Fc fusion protein). The administration of the novel antiplatelet agent Revacept to C57BL/6 mice, beginning three days before femoral artery denudation, and continuing up to seven days after injury, prevented the increase of the systemic biosynthesis di TXA2 and reduced femoral artery intima-to-media area and the levels of markers of cell proliferation and macrophage infiltration. Revacept might serve as a therapeutic agent for percutaneous coronary angioplasty and stent implantation.Sara AlbertiQianqian ZhangIlaria D’AgostinoAnnalisa BrunoStefania TacconelliAnnalisa ContursiSimone GuarnieriMelania DovizioLorenza FalconePatrizia BalleriniGötz MünchYing YuPaola PatrignaniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Sara Alberti
Qianqian Zhang
Ilaria D’Agostino
Annalisa Bruno
Stefania Tacconelli
Annalisa Contursi
Simone Guarnieri
Melania Dovizio
Lorenza Falcone
Patrizia Ballerini
Götz Münch
Ying Yu
Paola Patrignani
The antiplatelet agent revacept prevents the increase of systemic thromboxane A2 biosynthesis and neointima hyperplasia
description Abstract Neointima hyperplasia is a crucial component of restenosis after coronary angioplasty. We have hypothesized that enhanced generation of platelet-derived thromboxane (TX)A2 in response to vascular damage plays a critical role in neointimal hyperplasia and that antiplatelet agents may mitigate it. In cocultures of human platelets and coronary artery smooth muscle cells (CASMC), we found that platelets induced morphologic changes and enhanced the migration of CASMC. The exposure of platelets to Aspirin [an inhibitor of cyclooxygenase (COX)-1] reduced the generation of TXA2 and prevented the morphological and functional changes induced by platelets in CASMC. Platelet-derived TXA2 induced COX-2 and enhanced prostaglandin (PG)E2 biosynthesis in CASMC, a known mechanism promoting neointimal hyperplasia. COX-2 induction was prevented by different antiplatelet agents, i.e., Aspirin, the TP antagonist SQ29,548, or Revacept (a dimeric soluble GPVI-Fc fusion protein). The administration of the novel antiplatelet agent Revacept to C57BL/6 mice, beginning three days before femoral artery denudation, and continuing up to seven days after injury, prevented the increase of the systemic biosynthesis di TXA2 and reduced femoral artery intima-to-media area and the levels of markers of cell proliferation and macrophage infiltration. Revacept might serve as a therapeutic agent for percutaneous coronary angioplasty and stent implantation.
format article
author Sara Alberti
Qianqian Zhang
Ilaria D’Agostino
Annalisa Bruno
Stefania Tacconelli
Annalisa Contursi
Simone Guarnieri
Melania Dovizio
Lorenza Falcone
Patrizia Ballerini
Götz Münch
Ying Yu
Paola Patrignani
author_facet Sara Alberti
Qianqian Zhang
Ilaria D’Agostino
Annalisa Bruno
Stefania Tacconelli
Annalisa Contursi
Simone Guarnieri
Melania Dovizio
Lorenza Falcone
Patrizia Ballerini
Götz Münch
Ying Yu
Paola Patrignani
author_sort Sara Alberti
title The antiplatelet agent revacept prevents the increase of systemic thromboxane A2 biosynthesis and neointima hyperplasia
title_short The antiplatelet agent revacept prevents the increase of systemic thromboxane A2 biosynthesis and neointima hyperplasia
title_full The antiplatelet agent revacept prevents the increase of systemic thromboxane A2 biosynthesis and neointima hyperplasia
title_fullStr The antiplatelet agent revacept prevents the increase of systemic thromboxane A2 biosynthesis and neointima hyperplasia
title_full_unstemmed The antiplatelet agent revacept prevents the increase of systemic thromboxane A2 biosynthesis and neointima hyperplasia
title_sort antiplatelet agent revacept prevents the increase of systemic thromboxane a2 biosynthesis and neointima hyperplasia
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/e6a515e9c8494e3e985c043ce7cad9e0
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