BibTex format
@article{Mourikis:2025:10.1126/scitranslmed.ado061,
author = {Mourikis, P and Benkhoff, M and Wildeis, L and Barcik, M and Helten, C and Coman, C and Solari, FA and Krahn, D and Dannenberg, L and Ahlbrecht, S and Zikeli, D and Utz, A and Trojovsky, K and Richter, H and Al, Kassis G and MPembele, R and Zako, S and Huckenbeck, T and Bauer, S and Schmitz, D and Pfeiler, S and Gerdes, N and Dücker, C and Pircher, J and Zhe, Z and Thienel, M and Ul, Ain Q and Keul, P and Kirkby, N and Sohn, D and Budach, W and Hohlfeld, T and Schrör, K and Levkau, B and Zeus, T and Verhelst, SHL and Ahrends, R and Sickmann, A and Mitchell, J and Mora, S and Manson, JE and Bhatt, DL and Landmesser, U and Massberg, S and Kelm, M and Petzold, T and Polzin, A},
doi = {10.1126/scitranslmed.ado061},
journal = {Science Translational Medicine},
title = {Icosapent ethyl reduces arterial thrombosis by inhibition of cyclooxygenase-1 induced platelet reactivity},
url = {http://dx.doi.org/10.1126/scitranslmed.ado061},
volume = {17},
year = {2025}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Large, randomized trials testing omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation to reduce cardiovascular events have reported contradictory results. Interpretation of these trials is challenging, because different dosages and formulations of ω-3 PUFA were tested. Furthermore, the exact mechanisms for the reduction in cardiovascular events are unclear. In this study, we investigated the effects of ω-3 PUFA on platelet adhesion, degranulation, and aggregation in vitro and in patients with cardiovascular disease using different formulations of ω-3 PUFA. We also investigated the effects of ω-3 PUFA in rodent models of arterial thrombosis and in tail bleeding assays, including in cyclooxygenase-1 (COX-1)–deficient animals. The ω-3 PUFA eicosapentaenoic acid (EPA) dose-dependently reduced platelet adhesion, degranulation, and aggregation in vitro. Moreover, arterial thrombus formation in wild-type mice was inhibited by oral EPA administration before thrombus formation. Photoaffinity labeling and in silico docking analyses suggested a direct, competitive interaction of EPA and arachidonic acid at the level of COX-1. The COX-1 dependency of EPA’s inhibitory effects was confirmed by platelet-specific COX-1–deficient animals that had no reduction of thrombus burden by EPA. In patients with cardiovascular disease, switching from 2 grams of EPA twice daily to 1 gram of docosahexaenoic acid (DHA) (460 milligrams of EPA and 380 milligrams of DHA) once daily completely blunted the platelet inhibition achieved by EPA. Our results may partially explain contradictory results with different ω-3 PUFA formulations in clinical trials.
AU - Mourikis,P
AU - Benkhoff,M
AU - Wildeis,L
AU - Barcik,M
AU - Helten,C
AU - Coman,C
AU - Solari,FA
AU - Krahn,D
AU - Dannenberg,L
AU - Ahlbrecht,S
AU - Zikeli,D
AU - Utz,A
AU - Trojovsky,K
AU - Richter,H
AU - Al,Kassis G
AU - MPembele,R
AU - Zako,S
AU - Huckenbeck,T
AU - Bauer,S
AU - Schmitz,D
AU - Pfeiler,S
AU - Gerdes,N
AU - Dücker,C
AU - Pircher,J
AU - Zhe,Z
AU - Thienel,M
AU - Ul,Ain Q
AU - Keul,P
AU - Kirkby,N
AU - Sohn,D
AU - Budach,W
AU - Hohlfeld,T
AU - Schrör,K
AU - Levkau,B
AU - Zeus,T
AU - Verhelst,SHL
AU - Ahrends,R
AU - Sickmann,A
AU - Mitchell,J
AU - Mora,S
AU - Manson,JE
AU - Bhatt,DL
AU - Landmesser,U
AU - Massberg,S
AU - Kelm,M
AU - Petzold,T
AU - Polzin,A
DO - 10.1126/scitranslmed.ado061
PY - 2025///
SN - 1946-6234
TI - Icosapent ethyl reduces arterial thrombosis by inhibition of cyclooxygenase-1 induced platelet reactivity
T2 - Science Translational Medicine
UR - http://dx.doi.org/10.1126/scitranslmed.ado061
VL - 17
ER -