Abstract
Platelet activation contributes to the alteration of endothelial function, a critical initial step in atherogenesis through the production and release of prooxidant mediators. There is uncertainty about the precise role of polyphenols in interaction between platelets and endothelial cells (ECs). We aimed to investigate whether polyphenols are able to reduce endothelial activation induced by activated platelets. First, we compared platelet activation and flow-mediated dilation (FMD) in 10 healthy subjects (HS) and 10 patients with peripheral artery disease (PAD). Then, we evaluated the effect of epicatechin plus catechin on platelet-HUVEC interaction by measuring soluble cell adhesion molecules (CAMs), NOx production, and eNOS phosphorylation (p-eNOS) in HUVEC. Compared to HS, PAD patients had enhanced platelet activation. Conversely, PAD patients had lower FMD than HS. Supernatant of activated platelets from PAD patients induced an increase of sCAMs release and a decrease of p-eNOS and nitric oxide (NO) bioavailability compared to unstimulated HUVEC. Coincubation of HUVEC, with supernatant of PAD platelets patients, pretreated with a scalar dose of the polyphenols, resulted in a decrease of sCAMs release and in an increase of p-eNOS and NO bioavailability. This study demonstrates that epicatechin plus catechin reduces endothelial activation induced by activated platelets.
Highlights
peripheral artery disease (PAD) patients showed higher platelet reactive oxygen species (ROS) production (10.6 ± 1.4 SI versus 3.4 ± 0.9 SI, ∗P < 0.001) (Figure 1(a)), H2O2 concentration (18.4 ± 0.7 μM versus 5.4 ± 0.5 μM, ∗P < 0.001) (Figure 1(b)), sNOX2-dp release (29.8 ± 13.4 pg/mL versus 7.9 ± 2.3 pg/mL, ∗P < 0.001) (Figure 1(c)), and 8iso-PGF2α production (162.6 ± 42.8 pmol/L versus 67.0 ± 6.4 pmol/L, ∗P < 0.001) (Figure 1(d)) compared to healthy subjects (HS)
The major findings of this paper are as follows: (a) PAD patients show higher platelet activation than HS; (b) supernatant of activated platelets derived from PAD patients (SAPAD) is able to activate endothelial cells (ECs), resulting in an upregulation of soluble molecules derived from ECs; (c) PAD platelets induced ECs activation by reduction of p-eNOS and bioavailability of nitric oxide (NO); (d) polyphenols are able to reduce endothelial activation induced by activated platelets
Previous findings showed that in PAD patients there is an imbalance between NOX2-mediated oxidative stress and flow-mediated dilation (FMD) [11]
Summary
Atherosclerosis develops progressively through continuous evolution of arterial wall lesions due to the accumulation of cholesterolrich lipids and the associated inflammatory response [1]. It is clear that functional or morphological alterations in endothelial cells (ECs), platelets, and leukocytes appear to be critical in the evolution, progression, and clinical manifestation of the atherosclerosis [2]. Their interaction plays an important role and represents a key event, triggering and sustaining the inflammatory process in the arterial wall [2]. Such interplay between platelets and endothelium affects the entire course of development of atherosclerosis
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