Platelet, not endothelial, P-selectin is required for neointimal formation after vascular injury.

Abstract

BACKGROUND:

P-selectin blockade significantly inhibits inflammation and neointimal formation after arterial injury; however, the independent roles of platelet and endothelial P-selectins in this process are unknown. In atherosclerosis, both platelet and endothelial cell P-selectins are important. This study was designed to determine whether P-selectin expression on platelet, endothelial, or both surfaces is critical to the inflammatory response and neointimal formation after arterial injury.

METHODS AND RESULTS:

Using wild-type (WT) and P-selectin-knockout (Psel(-/-)) mice, we performed bone marrow transplantation to generate chimeric mice that expressed either platelet P-selectin (Plt-Psel) or endothelial P-selectin (EC-Psel). Double injury of the carotid artery was performed in these mice as well as in WT and Psel(-/-) mice. Animals were euthanized 4 or 21 days after arterial injury. Morphometric data showed that there was more neointimal formation in the WT mouse group when compared with the Psel(-/-) mouse group (0.015+/-0.004 vs 0.004+/-0.004 mm2, P<0.001). Further comparison showed significantly less neointimal area in EC-Psel mice (0.006+/-0.004 mm2) compared with Plt-Psel mice (0.011+/-0.005 mm2, P=0.026) and WT mice (0.015+/-0.004 mm2, P=0.001). No significant differences were observed between WT and Plt-Psel mice or between Psel(-/-) and EC-Psel mice. Decreased neointimal formation was accompanied by a reduced inflammatory response, as evidenced by immunostaining of RANTES and MCP-1 4 days after injury.

CONCLUSIONS:

Platelet P-selectin expression, but not endothelial P-selectin, plays a crucial role in the development of neointimal formation after arterial injury, and therapeutic strategies targeting leukocyte-platelet interactions could be effective in inhibiting restenosis.

• Authors: Kai Wang, Xiaorong Zhou, Zhongmin Zhou, Niladri Mal, Liming Fan, Ming Zhang, A Michael Lincoff, Edward F Plow, Eric J Topol, Marc S Penn
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 25 Issue 8 Pg. 1584-9 (Aug 2005) ISSN: 1524-4636 [Electronic] United States
• PMID: 15947246 (Publication Type: Journal Article)

Chemical References

• Chemokine CCL2
• Chemokine CCL5
• P-Selectin
• Peptide Fragments
• monocyte chemoattractant protein 1 (9-76)

Topics

• Angioplasty, Balloon (adverse effects)
• Animals
• Blood Platelets (metabolism)
• Bone Marrow Transplantation
• Carotid Artery Injuries (immunology, metabolism, pathology)
• Carotid Artery, Common (immunology, metabolism, pathology)
• Chemokine CCL2 (metabolism)
• Chemokine CCL5 (metabolism)
• Endothelium, Vascular (immunology, metabolism, pathology)
• Hyperplasia
• Immunohistochemistry
• Macrophages (pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Monocytes (pathology)
• Neutrophils (pathology)
• P-Selectin (genetics, metabolism)
• Peptide Fragments (metabolism)
• Tunica Intima (immunology, metabolism, pathology)