A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion Formation

By Steffen Massberg, K. Brand, S. Grüner, S. Page, E. Müller, I. Müller, W. Bergmeier, T. Richter, M. Lorenz, Ildiko Konrad and 2 more. Journal of Experimental Medicine, 2002

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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)Ibα 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.

Subfields: Hematology, Immunology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/d2b3546af5bc7b4b2f5a28a86cc87288f4fcb64e

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Citations in the corpus

Diverse novel functions of neutrophils in immunity, inflammation, and beyond (2013, background): “Platelets were previously proposed to participate in atherosclerotic plaque formation (Massberg et al., 2002; Huo et al., 2003) and platelet-derived CCL5 was shown to promote monocyte adhesion to the luminal surface of early atherosclerotic lesions in the inflamed arterial wall in mice (von…”
ADAM‐15: a metalloprotease that mediates inflammation (2008, background): “Other studies (18, 27) have pointed out that ADAM-15 is also involved in atherosclerosis through platelets that appear to play a critical role in the initiation of atherosclerotic lesions (28).”
Platelets in Inflammation and Atherogenesis (2015, background): “PLATELET CONTRIBUTION TO ATHEROSCLEROSIS In atherosclerosis, platelets are known to contribute to early steps of this chronic vascular pathology (Figure 2) such as endothelial dysfunction (101, 102), but also to final events such as rupture of the vulnerable plaque [(103), see also Figure 4].”
Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo (2012, methodology): “Murine platelets were isolated from whole blood and labeled with 5-carboxyflourescein diacetate succinimidyl ester (DCF) or cell tracker violet (Invitrogen) as reported earlier (Massberg et al., 2002).”