Abstract
The risks for adverse thrombotic events, including myocardial infarction, stroke, and deep vein thrombosis, are markedly increased in dyslipidemia and other metabolic disorders and are the major cause of death worldwide. Recent evidence points out that increased thrombotic risk in dyslipidemia is mediated by platelets circulating in a pre-activated state. The mechanisms of platelet reactivity in this setting are multifaceted including platelet activation by classic agonist receptor signaling as well as platelet sensitization by pattern recognition receptors. Elevated platelet counts in dyslipidemia due to dysregulation in hematopoiesis also contribute to the overall thrombotic phenotype. Despite recent advancements in antiplatelet and anticoagulation therapies, recurrences of adverse thrombotic events remain to be a large clinical burden. In the light of new knowledge, understanding mechanisms that drive pathologic thrombosis in dyslipidemia, the antithrombotic approach shall be revisited. Here, we discuss potential therapeutic avenues based on the overview of platelet signaling mechanisms that contribute to a prothrombotic phenotype in dyslipidemia.
Highlights
Adverse thrombotic events account for 1 in for 4 deaths worldwide and represent a major clinical burden [1]
We focus on two major types of receptors here, the collagen receptor glycoprotein VI (GPVI) and protease-activated receptors (PARs) 1 and 4 as potent platelet activation pathways that are intimately linked to procoagulant functions
No differences were observed in platelet adhesion onto collagen-coated surfaces nor other extracellular matrixcoated surfaces in GPVI homozygous or heterozygous deficiency [18]. This suggests that GPVI may participate in selective platelet functions beyond its classic role as a platelet adhesion receptor
Summary
Adverse thrombotic events account for 1 in for 4 deaths worldwide and represent a major clinical burden [1]. Much of the focus has been on specific pattern recognition receptors present on platelets and how these pathways crosstalk with classic agonist stimulation As these “non-classical” signaling pathways are induced only during the dyslipidemic state, understanding these pathways could pinpoint therapeutic targets for atherothrombosis without compromising hemostasis. Anisms by which there is an increased platelet number in dyslipidemia is poorly understood compared to the mechanisms of platelet activation in this condition Thrombocytosis in these settings is likely linked to the sensitivity of the bone marrow niche to cholesterol. We outline potential therapeutic approaches for antiplatelet therapy in dyslipidemia based on current knowledge of atherothrombosis
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