Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E
Yuqing Huo1, Andreas Schober, S Bradley Forlow
1Department of Biomedical Engineering and Cardiovascular Research Center, University of Virginia, Health Science Center, Charlottesville, Virginia, USA.
Nature Medicine
|December 17, 2002
Summary
Circulating activated platelets and platelet-leukocyte aggregates promote atherosclerosis development. Platelet P-selectin delivers inflammatory factors, increasing lesion size and monocyte binding in Apoe(-/-) mice.
Area of Science:
- Cardiovascular biology
- Immunology
- Hematology
Background:
- Atherosclerosis is a chronic inflammatory disease characterized by plaque buildup in arteries.
- The role of activated platelets and their interactions with leukocytes in atherosclerosis pathogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the contribution of circulating activated platelets and platelet-leukocyte aggregates to atherosclerotic lesion development in apolipoprotein-E-deficient (Apoe(-/-)) mice.
Main Methods:
- Studied interactions between activated platelets, leukocytes (preferentially monocytes), and atherosclerotic lesions in Apoe(-/-) mice.
- Administered activated wild-type or P-selectin-deficient platelets and assessed monocyte recruitment and lesion size.
- Analyzed the delivery of platelet-derived chemokines (CCL5, CXCL4) and the role of P-selectin and vascular cell adhesion molecule-1 (VCAM-1).
Main Results:
- Activated platelets formed aggregates with leukocytes, particularly monocytes, which interacted with atherosclerotic lesions.
- Platelet-chemokines CCL5 and CXCL4 were delivered to monocytes and the arterial endothelium.
- Activated platelets enhanced leukocyte binding via VCAM-1 and increased leukocyte adhesion to inflamed endothelium.
- Injection of activated wild-type platelets, but not P-selectin-deficient platelets, increased monocyte arrest and atherosclerotic lesion size.
Conclusions:
- Circulating activated platelets and platelet-leukocyte aggregates are key drivers of atherosclerotic lesion formation.
- Platelet P-selectin mediates the delivery of pro-inflammatory factors, promoting leukocyte recruitment and exacerbating atherosclerosis.
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