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

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.

Keywords: Cardiovascular disease; endothelial function; platelet function.

Figure 1

Individual responses for MPAs no agonist (NA) versus flow‐mediated dilation (FMD%) and results of correlation analysis. N = 51.

Figure 2

Individual responses for platelet PAC‐1 binding no agonist (NA) versus flow‐mediated dilation (FMD%) and results of correlation analysis. N = 50.

Figure 3

Individual responses for platelet anti‐CD62P binding no agonist (NA) versus flow‐mediated dilation (FMD%) and results of correlation analysis. N = 50.