oa Editorial [Hot Topic:Platelets in Inflammation and Inflammatory Disorders Guest Editor: Armen Yuri Gasparyan ]

Over the past few decades, our understanding of the molecular basis of the platelet production and function has substantially advanced. It has become clear that these anucleate cells are not just passively circulating fragments of megakaryocytes, but functionally active, autonomous agents, capable of producing a range of humoral mediators [1]. Though initially platelets were viewed as contributors to hemostasis and wound repair, advances in flow cytometry and proteomics research have identified numerous bioactive platelet proteins and broadened the scope of platelet-mediated physiological and pathological conditions [2]. Platelet membrane is full of functionally active proteins, facilitating platelet adhesion, aggregation and interaction with other blood and vascular cells. Examples of the critical importance of these membranous proteins are autosomal recessive hemorrhagic disorders caused by qualitative and quantitative changes of glycoprotein (GP) IIb/IIIa in Glazmann's thrombasthenia [3, 4] and by defect of GPIb/IX/V in Bernard-Soulier syndrome [5, 6]. On the other hand, genetically determined changes of these and other platelet receptors (e.g., GPIa/IIa and GPVI) predispose to unresponsiveness to antithrombotic agents, resulting in thrombotic events [7, 8]. Additionally, platelets have been found to express proteins belonging to the Toll-like receptors family, thereby facilitating the defense of the human organism against infectious agents [9, 10]. Structures inside the platelet, particularly alpha-, dense granules and lysosomes, are now well characterized. Alpha-granules are known to produce hundreds of bioactive proteins involved in the initiation and propagation of diverse thrombotic, inflammatory, immune, and metabolic disorders [11]. Some of the well-described proteins stored in and released from alphagranules are P-selectin, fibrinogen, von Willebrand factor, beta-thromboglobulin, CD40 ligand, and transforming growth factorbeta. These and many other proteins derived from alpha-granules play multiple, at times opposite roles, thus facilitating the involvement of activated platelets in a wide range of disorders. The multifaceted role of platelets and its agents has been comprehensively described within the frames of atherosclerosis, where immune, inflammatory and thrombotic pathways are intimately interrelated [12-14]. Some of the platelet agents released from alpha-granules (e.g., CD40 ligand) have been found to possess both pro-inflammatory and pro-thrombotic properties and to be independently associated with atherothrombotic events [15]. Evidence is also accumulating regarding the proinflammatory and pro-thrombotic roles of platelet-derived microparticles [16]. These microparticles are abundantly produced in conditions associated with vascular inflammation, such as acute coronary syndromes, vascular interventions, and diabetes, where the interaction of immune and inflammatory mechanisms brings about thrombosis [17]. Importantly, platelet-derived microparticles may also link inflammation with joint involvement in rheumatic diseases, particularly in rheumatoid arthritis [18]. Recently, several lines of evidence have appreciated the crucial role of activated platelets in cardiovascular involvement in rheumatoid arthritis [19] and some other autoimmune disorders [20]. A bulk of available evidence suggests that activated platelets are emerging targets of anti-inflammatory and antithrombotic therapies in rheumatic diseases [21-23]. Given the fact that functional characteristics of circulating platelets are predetermined at the stage of megakaryocytopoiesis [24], it is possible to speculate that optimal antithrombotic strategies in rheumatic and other chronic inflammatory disorders will target the megakaryocyte-platelet-microparticles axis. In this regard, the size of circulating platelets, reflecting the level of platelets production and their activity [25], may well serve as a means for monitoring antithrombotic therapies. The appreciation of platelets pro-inflammatory and pro-thrombotic roles has fueled interest toward the effects of antiplatelet agents, such as aspirin, clopidogrel, prasugrel, and abciximab, on both platelet activity and systemic inflammation [26]. Antiplatelet agents are capable of suppressing systemic and vascular inflammation by inhibiting platelet function and synthesis of platelets' inflammatory agents [27]. There is some preliminary evidence in favor of direct anti-inflammatory (pleiotropic) action of antiplatelet agents [26], which still needs confirmation in large and long-term trials [28]. It should be, however, bear in mind that anti-inflammatory potential of antiplatelet agents is limited, and in certain inflammatory conditions, such as coronary interventions, diabetes and rheumatoid arthritis, the issue of antiplatelet unresponsiveness can arise [8, 29, 30], necessitating additional monitoring of inflammatory markers and more aggressive suppression of systemic inflammation. The interrelation between platelets and inflammatory agents is also a big issue in the context of atherosclerotic disease in certain “high-risk” cohorts of patients. In particular, it has been shown that South Asians are genetically predisposed to accelerated atherosclerosis, type 2 diabetes and the metabolic syndrome, all of which are strongly associated with elevated markers of systemic inflammation [31, 32]. A few, relatively small studies have specifically investigated platelet-derived markers and platelet-monocyte complexes in this ethnic group compared to relevant controls [33, 34]. Though it is highly likely that activated platelets contribute to accelerated atherosclerosis in South Asians, the obtained evidence is still inconclusive on whether there are platelet-mediated pathways specific for this high-risk ethnic group. Further research is apparently needed to provide recommendations on antiplatelet therapies in South Asians [35]. Additionally, occupational and environmental exposure to diverse air pollutants, causing oxidative stress, platelet activation and inflammation [36, 37], should be taken into account when preventive strategies are planned. The latter is of particular importance in most vulnerable pediatric subjects [38] and those with underlying heightened cardiometabolic risk [39].........