Abstract
Given the high morbidity and mortality of cardiovascular diseases (CVDs), novel biomarkers for platelet reactivity are urgently needed. Ischemic events in CVDs are causally linked to platelets, small anucleate cells important for hemostasis. The major side-effect of antiplatelet therapy are life-threatening bleeding events. Current platelet function tests are not sufficient in guiding treatment decisions. Platelets host a broad spectrum of microRNAs (miRNAs) and are a major source of cell-free miRNAs in the blood stream. Platelet-related miRNAs have been suggested as biomarkers of platelet activation and assessment of antiplatelet therapy responsiveness. Platelets release miRNAs upon activation, possibly leading to alterations of plasma miRNA levels in conjunction with CVD or inadequate platelet inhibition. Unlike current platelet function tests, which measure platelet activation ex vivo, signatures of platelet-related miRNAs potentially enable the assessment of in vivo platelet reactivity. Evidence suggests that some miRNAs are responsive to platelet inhibition, making them promising biomarker candidates. In this review, we explain the secretion of miRNAs upon platelet activation and discuss the potential use of platelet-related miRNAs as biomarkers for CVD and antiplatelet therapy monitoring, but also highlight remaining gaps in our knowledge and uncertainties regarding clinical utility. We also elaborate on technical issues and limitations concerning plasma miRNA quantification.
Highlights
Platelets constitute the second most abundant cell type in blood and are key players in hemostasis and thrombosis
Even though a connection between putative platelet-related miRNAs and cardiovascular diseases (CVDs) has been established over the past years, respective miRNAs need to be rigorously validated and assessed for their capacity to serve as biomarkers
We discussed four of the most pressing questions concerning the development of a novel miRNA-based biomarker for platelet activation: 6. Conclusions
Summary
Platelets constitute the second most abundant cell type in blood and are key players in hemostasis and thrombosis. Standard platelet function tests (PFTs) are routinely used to assess platelet activation in CVD patients. Several publications have reported no benefit for patient outcome (reviewed by [17]), whereas other studies and meta-analyses have found PFT guidance in antiplatelet treatment potentially beneficial [19,20,21]. The evaluation of the platelet activation status on antiplatelet therapy might identify patients with inadequate response to platelet inhibition and increased risk for ischemic or thrombotic events [19,20,27]. It could help to identify patients with an excessive response to platelet inhibition and higher risk of bleeding complications. A reliable miRNA-based biomarker for platelet activation might improve efficient and safe use of antiplatelet drugs and allow the assessment of the in vivo status of platelets.
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