Aspirin enhances protective effect of fish oil against thrombosis and injury‐induced vascular remodelling

Abstract

Background and Purpose Although aspirin (acetylsalicylic acid) is commonly used to prevent ischaemic events in patients with coronary artery disease, many patients fail to respond to aspirin treatment. Dietary fish oil (FO), containing ω3 polyunsaturated fatty acids (PUFAs), has anti‐inflammatory and cardio‐protective properties, such as lowering cholesterol and modulating platelet activity. The objective of the present study was to investigate the potential additional effects of aspirin and FO on platelet activity and vascular response to injury. Experimental Approach Femoral arterial remodelling was induced by wire injury in mice. Platelet aggregation, and photochemical‐ and ferric chloride‐induced carotid artery thrombosis were employed to evaluate platelet function. Key Results FO treatment increased membrane ω3 PUFA incorporation, lowered plasma triglyceride and cholesterol levels, and reduced systolic BP in mice. FO or aspirin alone inhibited platelet aggregation; however, when combined, they exhibited synergistic suppression of platelet activity in mice, independent of COX‐1 inhibition. FO alone, but not aspirin, attenuated arterial neointimal growth in response to injury. Strikingly, a combination of FO and aspirin synergistically inhibited injury‐induced neointimal hyperplasia and reduced perivascular inflammatory reactions. Moreover, co‐administration of FO and aspirin decreased the expression of pro‐inflammatory cytokines and adhesion molecules in inflammatory cells. Consistently, a pro‐resolution lipid mediator‐Resolvin E1, was significantly elevated in plasma in FO/aspirin‐treated mice. Conclusions and Implications Co‐administration of FO and low‐dose aspirin may act synergistically to protect against thrombosis and injury‐induced vascular remodelling in mice. Our results support further investigation of adjuvant FO supplementation for patients with stable coronary artery disease. Linked Articles This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23

Endogenously Generated Omega‐3 Fatty Acids Attenuate Vascular Inflammation and Neointimal Hyperplasia by Interaction With Free Fatty Acid Receptor 4 in Mice

“…This result might be expected because mice were fed a ω6 PUFA diet, and the conversion efficiency of ω3 fatty acid desaturase may be limited. The ratio of ω3 PUFAs for fat‐1 and WT mice (≈5) in our study is much higher than that in fish oil–supplemented diet studies, 53 allowing us to address the effects of endogenously synthesized ω3 PUFAs in mice with the fat‐1 gene. Tissue‐ and cell‐specific FFAR4 knockout strains should further enhance insight into the roles of this receptor in future studies.…”

“…In this study, the ratio of ω6/ω3 PUFAs is higher in all 4 groups of mice, and the relative percentages of converted ω3 PUFAs in fat‐1 mice is likely lower than those in diet‐supplementation studies. 52–53 . This result might be expected because mice were fed a ω6 PUFA diet, and the conversion efficiency of ω3 fatty acid desaturase may be limited.…”

“…We showed previously that ω3 PUFA–rich fish oils favorably attenuate neointimal hyperplasia and improve cardiovascular function (platelet activity, blood pressure) by means of aspirin‐triggered resolvins. 53 ω3 PUFAs can also stimulate the generation of adiponectin through interaction with specific adipocyte channels 56 and may protect blood vessels from outside‐in damage in the pathogenesis of cardiovascular disorders. Furthermore, we and other researchers demonstrated that ω3 PUFAs (eg, DHA), through FFAR4 signaling, alter Toll‐like receptor 4–initiated pathways and limit inflammatory responses.…”

Resolution of vascular injury: Specialized lipid mediators and their evolving therapeutic implications

“…Effects on platelet aggregation, platelet-PMN interactions, and clot remodeling in-vivo have also demonstrated beneficial antithrombotic properties that are of clear relevance to vascular disease (Dona, Fredman et al 2008, Chen, Fenet et al 2009, Fredman and Serhan 2011, Gong, Lin et al 2015, Elajami, Colas et al 2016, Lannan, Spinelli et al 2017). Evidence for direct effects of SPM on EC and VSMC demonstrates an anti-inflammatory, homeostatic profile of actions that may constitute an important vasculo-protective biochemical pathway (Table 1).…”

Novel venous thromboembolic disease (VTED) prophylaxis for total knee arthroplasty—aspirin and fish oil

“…Longchain polyunsaturated fatty acids of fish oil can also function by competitive inhibition with arachidonic acid for the cyclooxygenase enzyme (25). These thromboprophylactic effects have also been found to be enhanced when fish oil is combined with aspirin (26)(27)(28). Therefore, fish oil can be a natural alternative medication, and play a marked role in VTE management in post-surgical patients.…”