Characterizing the anti-inflammatory and tissue protective actions of a novel Annexin A1 peptide

This work was supported by a collaborative project between Unigene Corp. and Queen Mary University of London and by the William Harvey Research Foundation. JD is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant no: 107613/Z/15/Z). MP was supported by the Wellcome Trust (grant no: 086867/Z/08)

Platelet Function and Coronary Microvascular Dysfunction

The ability of platelets to activate and aggregate to form blood clots in response to endothelial injury is well established. They are therefore critical contributors to ischaemia in atherothrombosis [1]. However, their role in cardiovascular disease is not limited to end-stage thrombosis in large vessels [2]. Abundant experimental evidence has established that activated platelets are also important mediators of microvascular thrombosis and promote the inflammatory response during ischaemia-reperfusion (IR) injury [3–5]. While platelets do not physically interact with the healthy endothelium, they can bind to the wall of hypoxic microvessels and release a plethora of inflammatory mediators that further enhance the activation of the endothelial monolayer and the recruitment of circulating leukocytes (monocytes, neutrophils, T-cells) [2]. In addition, deposition of platelets to the dysfunctional endothelium can lead to vasoconstriction which accelerates microvascular occlusion, thereby impairing tissue perfusion [3]. In this chapter, we discuss the role of platelets in promoting microvascular dysfunction and inflammation during IR injury. Focus is placed on the cross-talk between platelets and other cell types (endothelial cells [ECs] and leukocytes) via platelet adhesion receptors and platelet-derived proinflammatory mediators. We also consider new paradoxical functionalities of platelets promoting cardiac recovery after myocardial infarction (MI)

Specialized Pro-Resolving Mediators Directs Cardiac Healing and Repair with Activation of Inflammation and Resolution Program in Heart Failure

After myocardial infarction, splenic leukocytes direct biosynthesis of specialized pro-resolving mediators (SPMs) that are essential for the resolution of inflammation and tissue repair. In a laboratory environment, after coronary ligation of healthy risk free rodents (young adult mice) leukocytes biosynthesize SPMs with induced activity of lipoxygenases and cyclooxygenases, which facilitate cardiac repair. Activated monocytes/macrophages drive the biosynthesis of SPMs following experimental myocardial infarction in mice during the acute heart failure. In the presented review, we provided the recent updates on SPMs (resolvins, lipoxins and maresins) in cardiac repair that may serve as novel therapeutics for future heart failure therapy/management. We incorporated the underlying causes of non-resolving inflammation following cardiac injury if superimposed with obesity, hypertension, diabetes, disrupted circadian rhythm, co-medication (painkillers or oncological therapeutics), and/or aging that may delay or impair the biosynthesis of SPMs, intensifying pathological remodeling in heart failure