Relationship between monocyte-platelet aggregation and endothelial function in middle-aged and elderly adults.

Andrew Haynes,Kay L Cox,Nicola T Lautenschlager,Louise H Naylor,Matthew D Linden,Daniel J Green,Elisa Robey

doi:10.14814/phy2.13189

Abstract

Low‐grade inflammation, endothelial dysfunction, and platelet hyper‐reactivity to agonists are associated with an increased risk of cardiovascular events. In vitro and animal studies infer an inverse mechanistic relationship between platelet activation and the production of endothelium‐derived nitric oxide and prostacyclin. This concept is supported by evidence of an inverse relationship between endothelial function and platelet activation in high‐risk cardiac patients. The aim of this study was to investigate what relationship, if any, exists between platelet and endothelial function in healthy, middle‐aged, and elderly adults. In 51 participants (18 male, 33 post menopausal female), endothelial function was assessed by flow‐mediated dilation (FMD). Platelet function was assessed by flow cytometric determination of glycoprotein IIb/IIIa activation (measured by PAC‐1 binding), granule exocytosis (measured by surface P‐selectin expression), and monocyte‐platelet aggregates (MPAs), with and without stimulation by canonical platelet agonists adenosine diphosphate (ADP), arachidonic acid (AA), and collagen. Correlation analysis indicated there was no significant (all P => 0.05) relationship between FMD and any marker of in vivo platelet activation (MPAs R = 0.193, PAC‐1 R = −0.113, anti‐CD62P R = −0.078) or inducible platelet activation by ADP (MPA R = −0.128, anti‐CD62P R = −0.237), AA (MPA R = −0.122, PAC‐1 R = −0.045, anti‐CD62P R = −0.142), or collagen (MPA R = 0.136, PAC‐1 R = 0.174, anti‐CD62P R = −0.077). Our findings contrast with two previous studies performed in high‐risk cardiac patients, which reported inverse relationships between platelet activation and endothelial function, suggesting that some compensatory redundancy may exist in the relationship between platelet and endothelial function in preclinical populations.

Highlights

Thrombosis is an integral component of acute coronary syndromes such as acute myocardial infarction (MI) and ischemic stroke [12, 23]
An error in the processing of platelet PAC-1 and CD62P with no agonist occurred for 1 participant and for PAC-1 and CD62P with arachidonic acid (AA) incubation for 1 other participant
Endothelial dysfunction and increased platelet activation are both associated with cardiovascular disease progression [9, 10] and, based on in vitro and animal studies, it is often inferred that a direct and inverse relationship exists between the function of the endothelium and platelet activation [2, 3, 41, 42]

Summary

Introduction

Thrombosis is an integral component of acute coronary syndromes such as acute myocardial infarction (MI) and ischemic stroke [12, 23]. The role of platelets in the early, dormant stages of atherosclerosis and cardiovascular disease (CVD) has recently been recognized [26, 40]. Endothelial dysfunction and platelet hyperreactivity to agonists are all independently associated with an increased risk of cardiovascular events [15, 24]. An intact and healthy endothelium regulates and inhibits platelet activation [9] and endothelial dysfunction may play a direct role in activating platelets [8]. Platelet activation results in the formation of monocyte-platelet aggregates (MPAs) [27], and stepwise increases in MPAs and activated platelets have been observed with cardiovascular disease progression [28]. The interaction between activated platelets and monocytes can initiate the release of pro-inflammatory and adhesive molecules that are atherogenic [13, 30, 32, 50], driving a pro-atherogenic monocytic phenotype [4] and facilitating the infiltration of monocytes to the sub-intima space [30, 47]

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