Platelets Mediate Oxidized Low-Density Lipoprotein–Induced Monocyte Extravasation and Foam Cell Formation

Author:

Badrnya Sigrun1,Schrottmaier Waltraud C.1,Kral Julia B.1,Yaiw Koon-Chu1,Volf Ivo1,Schabbauer Gernot1,Söderberg-Nauclér Cecilia1,Assinger Alice1

Affiliation:

1. From the Institute of Physiology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria (S.B., W.C.S., J.B.K., I.V., G.S., A.A.); and Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden (K.-C.Y., C.S.-N., A.A.).

Abstract

Objective— A growing body of evidence indicates that platelets contribute to the onset and progression of atherosclerosis by modulating immune responses. We aimed to elucidate the effects of oxidized low-density lipoprotein (OxLDL) on platelet–monocyte interactions and the consequences of these interactions on platelet phagocytosis, chemokine release, monocyte extravasation, and foam cell formation. Approach and Results— Confocal microscopy and flow cytometric analysis revealed that in vitro and in vivo stimulation with OxLDL resulted in rapid formation of platelet–monocyte aggregates, with a preference for CD16+ monocyte subsets. This platelet–monocyte interaction facilitated OxLDL uptake by monocytes, in a process that involved platelet CD36–OxLDL interaction, release of chemokines, such as CXC motif ligand 4, direct platelet–monocyte interaction, and phagocytosis of platelets. Inhibition of cyclooxygenase with acetylsalicylic acid and antagonists of ADP receptors, P2Y1 and P2Y12, partly abrogated OxLDL-induced platelet–monocyte aggregates and platelet-mediated lipid uptake in monocytes. Platelets also enhanced OxLDL-induced monocyte transmigration across an endothelial monolayer via direct interaction with monocytes in a transwell assay. Importantly, in LDLR −/− mice, platelet depletion resulted in a significant decrease of peritoneal macrophage recruitment and foam cell formation in a thioglycollate-elicited peritonitis model. In platelet-depleted wild-type mice, transfusion of ex vivo OxLDL-stimulated platelets induced monocyte extravasation to a higher extent when compared with resting platelets. Conclusions— Our results on OxLDL-mediated platelet–monocyte aggregate formation, which promoted phenotypic changes in monocytes, monocyte extravasation and enhanced foam cell formation in vitro and in vivo, provide a novel mechanism for how platelets potentiate key steps of atherosclerotic plaque development and plaque destabilization.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

Reference58 articles.

1. From low-density lipoprotein to platelet activation

2. Isolation and partial characterization of an oxidized LDL in humans.;Avogaro P;Basic Life Sci,1988

3. Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man.

4. Beyond Cholesterol

5. Update on lipids, inflammation and atherothrombosis.;Badimon L;Thromb Haemost,2011

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