Abstract
Cardiovascular diseases (CVDs) are the leading cause of death globally—partly a consequence of increased population size and ageing—and are major contributors to reduced quality of life. Platelets play a major role in hemostasis and thrombosis. While platelet activation and aggregation are essential for hemostasis at sites of vascular injury, uncontrolled platelet activation leads to pathological thrombus formation and provokes thrombosis leading to myocardial infarction or stroke. Platelet activation and thrombus formation is a multistage process with different signaling pathways involved to trigger platelet shape change, integrin activation, stable platelet adhesion, aggregation, and degranulation. Apart from thrombotic events, thrombo-inflammation contributes to organ damage and dysfunction in CVDs and is mediated by platelets and inflammatory cells. Therefore, in the past, many efforts have been made to investigate specific signaling pathways in platelets to identify innovative and promising approaches for novel antithrombotic and anti-thrombo-inflammatory strategies that do not interfere with hemostasis. In this review, we focus on some of the most recent data reported on different platelet receptors, including GPIb-vWF interactions, GPVI activation, platelet chemokine receptors, regulation of integrin signaling, and channel homeostasis of NMDAR and PANX1.
Highlights
Cardiovascular diseases (CVDs) include ischemic heart disease, stroke, heart failure, peripheral arterial disease, and a number of other cardiac and vascular conditions
Platelet receptors have been exploited as therapeutic targets since decades
Residual platelet reactivity and incidences of bleeding among susceptible individuals often lead to fatal consequences as evident from the outcome of several clinical trials conducted with FDA-approved antiplatelet agents, like P2Y12 antagonists [161] clopidogrel, prasugrel, ticagrelor, and competitive inhibitors of PAR-1 against thrombin, i.e., vorapaxar (TRACER [162] and TRA2P [163,164,165])
Summary
Cardiovascular diseases (CVDs) include ischemic heart disease, stroke, heart failure, peripheral arterial disease, and a number of other cardiac and vascular conditions They are the leading cause of death globally. Ischemic CVDs such as myocardial infarction and stroke as well as infectious diseases are characterized by thrombotic and inflammatory events that contribute to both cell death and organ failure. This thrombo-inflammation is mediated by platelets and immune cells such as T cells, macrophages and neutrophils and triggers organ dysfunction [6,7,8]. Many efforts have been made to identify new molecular targets for anti-thrombotic and anti-thrombo-inflammatory therapy in the last years
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