Mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation and exploration of platelet proteome and lipidome

Abstract Hyperlipidemia is a well-established risk factor for cardiovascular diseases. Millions of people worldwide display mildly elevated levels of plasma lipids and cholesterol linked to diet and life-style. While the prothrombotic risk of severe hyperlipidemia has been established, the effects o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Johanna P. van Geffen, Frauke Swieringa, Kim van Kuijk, Bibian M. E. Tullemans, Fiorella A. Solari, Bing Peng, Kenneth J. Clemetson, Richard W. Farndale, Ludwig J. Dubois, Albert Sickmann, René P. Zahedi, Robert Ahrends, Erik A. L. Biessen, Judith C. Sluimer, Johan W. M. Heemskerk, Marijke J. E. Kuijpers
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1989a910cf91487588230cb6fcebb5c1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1989a910cf91487588230cb6fcebb5c1
record_format	dspace
spelling	oai:doaj.org-article:1989a910cf91487588230cb6fcebb5c12021-12-02T12:33:15ZMild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation and exploration of platelet proteome and lipidome10.1038/s41598-020-78522-92045-2322https://doaj.org/article/1989a910cf91487588230cb6fcebb5c12020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78522-9https://doaj.org/toc/2045-2322Abstract Hyperlipidemia is a well-established risk factor for cardiovascular diseases. Millions of people worldwide display mildly elevated levels of plasma lipids and cholesterol linked to diet and life-style. While the prothrombotic risk of severe hyperlipidemia has been established, the effects of moderate hyperlipidemia are less clear. Here, we studied platelet activation and arterial thrombus formation in Apoe −/− and Ldlr −/− mice fed a normal chow diet, resulting in mildly increased plasma cholesterol. In blood from both knockout mice, collagen-dependent thrombus and fibrin formation under flow were enhanced. These effects did not increase in severe hyperlipidemic blood from aged mice and upon feeding a high-fat diet (Apoe −/− mice). Bone marrow from wild-type or Ldlr −/− mice was transplanted into irradiated Ldlr −/− recipients. Markedly, thrombus formation was enhanced in blood from chimeric mice, suggesting that the hyperlipidemic environment altered the wild-type platelets, rather than the genetic modification. The platelet proteome revealed high similarity between the three genotypes, without clear indication for a common protein-based gain-of-function. The platelet lipidome revealed an altered lipid profile in mildly hyperlipidemic mice. In conclusion, in Apoe −/− and Ldlr −/− mice, modest elevation in plasma and platelet cholesterol increased platelet responsiveness in thrombus formation and ensuing fibrin formation, resulting in a prothrombotic phenotype.Johanna P. van GeffenFrauke SwieringaKim van KuijkBibian M. E. TullemansFiorella A. SolariBing PengKenneth J. ClemetsonRichard W. FarndaleLudwig J. DuboisAlbert SickmannRené P. ZahediRobert AhrendsErik A. L. BiessenJudith C. SluimerJohan W. M. HeemskerkMarijke J. E. KuijpersNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-17 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Johanna P. van Geffen Frauke Swieringa Kim van Kuijk Bibian M. E. Tullemans Fiorella A. Solari Bing Peng Kenneth J. Clemetson Richard W. Farndale Ludwig J. Dubois Albert Sickmann René P. Zahedi Robert Ahrends Erik A. L. Biessen Judith C. Sluimer Johan W. M. Heemskerk Marijke J. E. Kuijpers Mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation and exploration of platelet proteome and lipidome
description	Abstract Hyperlipidemia is a well-established risk factor for cardiovascular diseases. Millions of people worldwide display mildly elevated levels of plasma lipids and cholesterol linked to diet and life-style. While the prothrombotic risk of severe hyperlipidemia has been established, the effects of moderate hyperlipidemia are less clear. Here, we studied platelet activation and arterial thrombus formation in Apoe −/− and Ldlr −/− mice fed a normal chow diet, resulting in mildly increased plasma cholesterol. In blood from both knockout mice, collagen-dependent thrombus and fibrin formation under flow were enhanced. These effects did not increase in severe hyperlipidemic blood from aged mice and upon feeding a high-fat diet (Apoe −/− mice). Bone marrow from wild-type or Ldlr −/− mice was transplanted into irradiated Ldlr −/− recipients. Markedly, thrombus formation was enhanced in blood from chimeric mice, suggesting that the hyperlipidemic environment altered the wild-type platelets, rather than the genetic modification. The platelet proteome revealed high similarity between the three genotypes, without clear indication for a common protein-based gain-of-function. The platelet lipidome revealed an altered lipid profile in mildly hyperlipidemic mice. In conclusion, in Apoe −/− and Ldlr −/− mice, modest elevation in plasma and platelet cholesterol increased platelet responsiveness in thrombus formation and ensuing fibrin formation, resulting in a prothrombotic phenotype.
format	article
author	Johanna P. van Geffen Frauke Swieringa Kim van Kuijk Bibian M. E. Tullemans Fiorella A. Solari Bing Peng Kenneth J. Clemetson Richard W. Farndale Ludwig J. Dubois Albert Sickmann René P. Zahedi Robert Ahrends Erik A. L. Biessen Judith C. Sluimer Johan W. M. Heemskerk Marijke J. E. Kuijpers
author_facet	Johanna P. van Geffen Frauke Swieringa Kim van Kuijk Bibian M. E. Tullemans Fiorella A. Solari Bing Peng Kenneth J. Clemetson Richard W. Farndale Ludwig J. Dubois Albert Sickmann René P. Zahedi Robert Ahrends Erik A. L. Biessen Judith C. Sluimer Johan W. M. Heemskerk Marijke J. E. Kuijpers
author_sort	Johanna P. van Geffen
title	Mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation and exploration of platelet proteome and lipidome
title_short	Mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation and exploration of platelet proteome and lipidome
title_full	Mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation and exploration of platelet proteome and lipidome
title_fullStr	Mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation and exploration of platelet proteome and lipidome
title_full_unstemmed	Mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation and exploration of platelet proteome and lipidome
title_sort	mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation and exploration of platelet proteome and lipidome
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/1989a910cf91487588230cb6fcebb5c1
work_keys_str_mv	AT johannapvangeffen mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT fraukeswieringa mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT kimvankuijk mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT bibianmetullemans mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT fiorellaasolari mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT bingpeng mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT kennethjclemetson mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT richardwfarndale mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT ludwigjdubois mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT albertsickmann mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT renepzahedi mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT robertahrends mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT erikalbiessen mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT judithcsluimer mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT johanwmheemskerk mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome AT marijkejekuijpers mildhyperlipidemiainmiceaggravatesplateletresponsivenessinthrombusformationandexplorationofplateletproteomeandlipidome
_version_	1718393844624523264

Mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation and exploration of platelet proteome and lipidome

Ejemplares similares