Dataset Information


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 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.

SUBMITTER: van Geffen JP 

PROVIDER: S-EPMC7722935 | BioStudies | 2020-01-01

REPOSITORIES: biostudies

Similar Datasets

2021-01-08 | PXD020276 | Pride
2010-01-01 | S-EPMC2818809 | BioStudies
2007-01-01 | S-EPMC3042888 | BioStudies
1000-01-01 | S-EPMC4366535 | BioStudies
2013-01-01 | S-EPMC3434265 | BioStudies
2012-01-01 | S-EPMC3275345 | BioStudies
1000-01-01 | S-EPMC2685354 | BioStudies
2016-01-01 | S-EPMC5346022 | BioStudies
2017-01-01 | S-EPMC5623081 | BioStudies
2012-11-07 | E-GEOD-42061 | BioStudies