BACKGROUND: Plaque erosion is a cause of atherothrombosis that preferentially occurs on smooth muscle cell (SMC)- and proteoglycan-rich rather than lipid-rich plaques. However, its underlying mechanisms remain unknown. OBJECTIVE: To determine whether disturbed blood flow induces erosive injury and thrombus formation on SMC-rich neointima. METHODS: Three weeks after balloon injury, SMC-rich neointima with increased tissue factor (TF) activity developed in rabbit femoral arteries that were narrowed with a vascular occluder to disturb blood flow after stenosis. Neointimal injury and thrombus formation were assessed at 15, 30, and 180 min after the vascular narrowing. RESULTS: Endothelial detachment, platelet adhesion and neointimal cell apoptosis became evident at the post-stenotic regions of all femoral arteries (n = 5) within 15 min of narrowing. Mural thrombi composed of platelet and fibrin developed after 30 min, and then occlusive thrombi were generated in three out of five vessels after 180 min. The identical vascular narrowing of normal femoral arteries also induced endothelial detachment with small platelet thrombi at post-stenotic regions, but fibrin and occlusive thrombi did not develop. Computational simulation analysis indicated that oscillatory shear stress contributes to the development of erosive damage to the neointima. CONCLUSIONS: These results suggest that disturbed post-stenotic blood flow can induce erosive injury in SMC-rich plaques and promote thrombus formation that results in vascular events.
BACKGROUND: Plaque erosion is a cause of atherothrombosis that preferentially occurs on smooth muscle cell (SMC)- and proteoglycan-rich rather than lipid-rich plaques. However, its underlying mechanisms remain unknown. OBJECTIVE: To determine whether disturbed blood flow induces erosive injury and thrombus formation on SMC-rich neointima. METHODS: Three weeks after balloon injury, SMC-rich neointima with increased tissue factor (TF) activity developed in rabbit femoral arteries that were narrowed with a vascular occluder to disturb blood flow after stenosis. Neointimal injury and thrombus formation were assessed at 15, 30, and 180 min after the vascular narrowing. RESULTS: Endothelial detachment, platelet adhesion and neointimal cell apoptosis became evident at the post-stenotic regions of all femoral arteries (n = 5) within 15 min of narrowing. Mural thrombi composed of platelet and fibrin developed after 30 min, and then occlusive thrombi were generated in three out of five vessels after 180 min. The identical vascular narrowing of normal femoral arteries also induced endothelial detachment with small platelet thrombi at post-stenotic regions, but fibrin and occlusive thrombi did not develop. Computational simulation analysis indicated that oscillatory shear stress contributes to the development of erosive damage to the neointima. CONCLUSIONS: These results suggest that disturbed post-stenotic blood flow can induce erosive injury in SMC-rich plaques and promote thrombus formation that results in vascular events.
Authors: Grégory Franck; Thomas Mawson; Grasiele Sausen; Manuel Salinas; Gustavo Santos Masson; Andrew Cole; Marina Beltrami-Moreira; Yiannis Chatzizisis; Thibault Quillard; Yevgenia Tesmenitsky; Eugenia Shvartz; Galina K Sukhova; Filip K Swirski; Matthias Nahrendorf; Elena Aikawa; Kevin J Croce; Peter Libby Journal: Circ Res Date: 2017-04-20 Impact factor: 17.367
Authors: Ian C Campbell; Lucas H Timmins; Don P Giddens; Renu Virmani; Alessandro Veneziani; S Tanveer Rab; Habib Samady; Michael C McDaniel; Aloke V Finn; W Robert Taylor; John N Oshinski Journal: Cardiovasc Eng Technol Date: 2013-12 Impact factor: 2.495
Authors: Ian C Campbell; Jonathan D Suever; Lucas H Timmins; Alessandro Veneziani; Raymond P Vito; Renu Virmani; John N Oshinski; W Robert Taylor Journal: PLoS One Date: 2014-11-03 Impact factor: 3.240