Effects of Omega-3 Polyunsaturated Fatty Acids and Their Metabolites on Haemostasis-Current Perspectives in Cardiovascular Disease

Abstract

The beneficial effects of long-chain polyunsaturated omega-3 fatty acids (omega-3 PUFAs) in cardioprotection are widely known and generally accepted. In this literature review, we have focused on the known and postulated mechanisms of action of omega-3 PUFAs and their metabolites on various components of the haemostatic system, in particular on blood platelets and endothelium. We have also made an attempt to provide a comprehensive review of epidemiological studies with particular regard to clinical trials. Notably, the results of these studies are contradictory, and some of them failed to report the beneficial effects of taking or supplementing omega-3 PUFAs in the diet. A potential explanation, in our opinion, could be the need to use higher doses of omega-3 PUFAs and a proper ratio of omega-3 and omega-6 PUFAs. An additional problem which is difficult to solve is the use of a proper neutral placebo for interventional studies. Despite some controversies regarding the beneficial effects of supplementation of omega-3 PUFAs in cardiovascular disease, our review suggests that a promising aspect of future studies and applications is to focus on the anti-thrombotic properties of these compounds. An argument supporting this assumption is the recent use of omega-3 PUFAs as a supporting tool for the treatment of COVID-19 complications.

Keywords: COVID-19; DHA; EPA; PUFA; cardiovascular; endothelium; haemostasis; omega-3; platelet.

Figure 1

Association between metabolites of unsaturated fatty acids and platelets, as well as endothelial cells. Abbreviations: PLA₂: Phospholipase A₂; MaR1: Maresin 1; PGI₂: Prostacyclin; TXA₂, TXA₃: Thromboxanes; RvE1: Resolvin E1; RvD1: Resolvin D1; AA: Arachidonic acid; DHA: Docosahexaenoic acid; EPA: Eicosapentaenoic acid.

Figure 2

Mechanism of antiplatelet effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and their metabolites. Abbreviations: II-Va-Xa: Factors of prothrombin complex; AA: Arachidonic acid; COX: Cyclooxygenase; FL: Membrane phospholipids; GPVI: Collagen receptor; Giq: G proteins; PLA: Phospholipase; P2Y12: ADP receptor; TF: Tissue factor; TXA₂, TXA₃: Thromboxanes; RvE1: Resolvin E1.

Figure 3

Mechanisms of endothelium regulation mediated by EPA, DHA, and their metabolites. Abbreviations: ET-1: Endothelin 1; eNOS: Endothelial synthase of nitric oxide; ICAM: Intercellular adhesion molecule; MPs: Microparticles; oxLDL: Oxidized low-density lipoproteins; NO: Nitric oxide; PAI-1: Plasminogen activator inhibitor 1; t-PA: Tissue plasminogen activator; TNF-α: Tumour necrosis factor-α; VCAM: Vascular cell adhesion molecule.