Do platelets promote cardiac recovery after myocardial infarction: roles beyond occlusive ischemic damage

Abstract

Our understanding of platelet function has traditionally focused on their roles in physiological hemostasis and pathological thrombosis, with the latter being causative of vessel occlusion and subsequent ischemic damage to various tissues. In particular, numerous in vivo studies have implicated causative roles for platelets in the pathogenesis of ischemia-reperfusion (I/R) injury to the myocardium. However, platelets clearly have more complex pathophysiological roles, particularly as a result of the heterogeneous nature of biologically active cargo secreted from their granules or contained within released microparticles or exosomes. While some of these released mediators amplify platelet activation and thrombosis through autocrine or paracrine amplification pathways, they can also regulate diverse cellular functions within the localized microenvironment and recruit progenitor cells to the damage site to facilitate repair processes. Notably, there is evidence to support cardioprotective roles for platelet mediators during I/R injury. As such, it is becoming more widely appreciated that platelets fulfill a host of physiological and pathological roles beyond our basic understanding. Therefore, the purpose of this perspective is to consider whether platelets, through their released mediators, can assume a paradoxically beneficial role to promote cardiac recovery after I/R injury.

Platelets in cardiac ischaemia/reperfusion injury: a promising therapeutic target

“…MicroRNAs (miRNA) have been shown to play a pivotal role in this process. Several miRNAs are stored and released by platelets, 23 and can exert beneficial effects on cardiac I/R injury, e.g. miRNA-199a, 24 but others can also exert detrimental effects, e.g.…”

Platelet Contributions to Myocardial Ischemia/Reperfusion Injury

“…Besides the negative effects induced by platelet adhesion and aggregation as well as the platelet dependent leukocyte infiltration into the infarcted myocardium, constituents released by platelets may have beneficial effects on the integrity of the coronary endothelium and on cardiac function after IRI (79, 80). In isolated rat hearts perfusion with platelets or supernatant of aggregated platelets was shown to exhibit cardioprotective effects (46) that were partially attributed to serotonin, thromboxane A2 or adenin nucleotides and their ability to induce the release of cardiac microvascular endothelial NO and its associated tissue protecting effects (81, 82).…”

Platelets modulate multiple markers of neutrophil function in response to in vitro Toll-like receptor stimulation

“…Interestingly, this regulatory response has been characterized in a number of inflammatory diseases where platelets are also known to be predominant drivers of leukocyte infiltration and leukocyte-mediated inflammation [17–19]. The dynamicity in platelet responses may be a mechanism to enhance, and then temper, an inflammatory response [20] to prevent rampant host damage [11] and is also both context- and stimulus-dependent [11, 21].…”