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

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van Geffen, Johanna P. 
Swieringa, Frauke 
van Kuijk, Kim 
Tullemans, Bibian M. E. 
Solari, Fiorella A. 


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.


Funder: Alexander von Humboldt Foundation

Funder: Centre for Translational Molecular Medicine (CTMM), Innovative Coagulation Diagnostics

Funder: Cardiovascular Centre (HVC), Maastricht University Medical Centre


Article, /631/443/592/75, /631/443/592/1339, article

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Scientific Reports

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Nature Publishing Group UK
de.NBI BMBF initiative grants (031L0108A, 031A534B)