Activation of human platelets by misfolded proteins
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Publication date
2007
Authors
Herczenik, E.
Bouma, B.
Korporaal, J.A.
Strangi, R.
Zeng, Q.
Gros, Piet
van Eck, M.
van Berkel, T.J.C.
Gebbink, M.F.B.G.
Akkerman, J.W.N.
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Abstract
Objective: Protein misfolding diseases result from the deposition of insoluble protein aggregates that often contain fibrils called amyloid. Amyloids are found in Alzheimer disease, atherosclerosis, diabetes mellitus, and systemic amyloidosis,which are diseases where platelet activation might be implicated. Methods and Results:We induced amyloid properties in 6 unrelated proteins and found that all induced platelet aggregation in contrast to fresh controls. Amyloid-induced platelet aggregation was independent of thromboxane A2 formation and ADP secretion but enhanced by feedback stimulation through these pathways. Treatments that raised cAMP (iloprost), sequestered Ca2+ (BAPTA-AM) or prevented amyloid-platelet interaction (sRAGE, tissue-typeplasminogen activator [tPA]) induced almost complete inhibition. Modulation of the function of CD36 (CD36-/- mice), p38MAPK (SB203580), COX-1 (indomethacin), and glycoprotein Ib
Keywords
SDG 3 - Good Health and Well-being
Citation
Herczenik, E, Bouma, B, Korporaal, J A, Strangi, R, Zeng, Q, Gros, P, van Eck, M, van Berkel, T J C, Gebbink, M F B G & Akkerman, J W N 2007, 'Activation of human platelets by misfolded proteins', Arteriosclerosis, Thrombosis and Vascular Biology, vol. 27, pp. 1657-1665.