A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation.
The contribution of platelets to the process of atherosclerosis remains unclear. Here, we show in vivo that platelets adhere to the vascular endothelium of the carotid artery in ApoE(-)(/)(-) mice before the development of manifest atherosclerotic lesions. Platelet-endothelial cell interaction involved both platelet glycoprotein (GP)Ibalpha and GPIIb-IIIa. Platelet adhesion to the endothelium coincides with inflammatory gene expression and preceded atherosclerotic plaque invasion by leukocytes. Prolonged blockade of platelet adhesion in ApoE(-)(/)(-) mice profoundly reduced leukocyte accumulation in the arterial intima and attenuated atherosclerotic lesion formation in the carotid artery bifurcation, the aortic sinus, and the coronary arteries. These findings establish the platelet as a major player in initiation of the atherogenetic process.
Massberg
Steffen
S
Deutsches Herzzentrum und 1. Medizinische Klinik, Technische Universität München, Germany. massberg@dhm.mhn.de
Brand
Korbinian
K
Grüner
Sabine
S
Page
Sharon
S
Müller
Elke
E
Müller
Iris
I
Bergmeier
Wolfgang
W
Richter
Thomas
T
Lorenz
Michael
M
Konrad
Ildiko
I
Nieswandt
Bernhard
B
Gawaz
Meinrad
M
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D001161:Arteriosclerosis / Q000097:blood / Q000473:pathology*; D039481:CD11b Antigen / Q000097:blood / Q000235:genetics; D002339:Carotid Arteries / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010973:Platelet Adhesiveness / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics
D001057:Apolipoproteins E; D039481:CD11b Antigen; D019039:Platelet Glycoprotein GPIIb-IIIa Complex