Acetylsalicylate reduces endothelial and platelet-derived microparticles in patients with coronary artery disease

Abstract

Previous studies suggest that endothelial progenitor cells (EPCs) contribute to vascular repair processes. In contrast, circulating microparticles (MPs) are reported to be part of a process that is damaging to vascular cells. Numerous studies suggest that the "balance" between EPCs and MPs is important for the integrity of vascular cells and preservation of endothelial function. In the present study, we assess the impact of acetylsalicylate (ASA) - which is, beside statins and physical exercise, a third basic column in the preventive therapy of coronary artery disease (CAD) - on EPCs and MPs in patients with CAD. We investigated the effect of treatment (8 weeks) with ASA (100 mg/d) on endothelial function (flow-mediated vasodilation, FMD), number of circulating EPCs, and endothelial- and platelet-derived microparticles (eMP, pMP) in 15 male patients (age 59.5 ± 12.3 years) with CAD but nonsignificant stenosis. The number of pMPs and eMPs decreased by 62.7% (p < 0.05) and 28.4% (p < 0.05), respectively. The number of circulating EPCs (VEGFR2(+)CD34(+)), expressed as ‰ of circulating polymorphonuclear leukocytes, remained unchanged. Despite the reduced number of pMPs and eMPs in response to the ASA therapy, the FMD responses and the maximal dilator effects of nitroglycerin were unaffected. In a control experiment, patients (n = 6) treated with the selective COX-2 inhibitor etoricoxib (90 mg/day) for 8 weeks showed no changes in the number of pMPs, eMPs, and EPCs and in FMD. We report on a novel effect of ASA treatment on the number of circulating endothelial- and platelet-derived microparticles in patients with cardiovascular disease. The mechanism remains elusive, and appears not to be associated with the COX-2 pathway.

Flow analysis of individual blood extracellular vesicles in acute coronary syndrome

“…Furthermore, we did not find any difference in the number of EVs between a few ASC patients whose blood was collected two hours after the start of therapy start and the rest of the cohort, however, this conclusion was based on a relatively small number of cases. Moreover, the anti-platelet therapy would rather decrease the number of the released EVs in patients compared to healthy controls, while we and others [41,53,54] observed the opposite effect, that is the increase of the number of various EVs in patients’ blood compared to healthy control. Thus, the described difference in EVs seems to be a part of the pathological process rather than the result of treatment.…”

Role of Platelet-Derived Microvesicles As Crosstalk Mediators in Atherothrombosis and Future Pharmacology Targets: A Link between Inflammation, Atherosclerosis, and Thrombosis

“…Thus, pMVs are susceptible targets for pharmacological modulation and offer new options for therapies specifically focused on lowering MV levels. For instance, anti-platelets drugs such as GPIIb/IIIa inhibitors (Goto et al, 2003; Morel et al, 2004), acetilsalicilic acid (Bulut et al, 2011), and clopidogrel (Judge et al, 2010; Franca et al, 2012), and the anti-diabetic drug ticlopidine (Nomura et al, 2004c) have shown to reduce pMVs. In patients under antithrombotic treatment, pMVs exposing CD62P or CD142 are still elevated 6 months after initiation of the therapy (Skeppholm et al, 2012), possibly due to the fact that low-dose of acetilsalicilic acid might not be strong enough to suppress shedding of pMVs into the microcirculation (Lubsczyk et al, 2010).…”

Endothelial microparticles: Sophisticated vesicles modulating vascular function

“…Patients with coronary artery disease under an 8-week regimen of acetylsalicylate (aspirin) 100 mg per day, showed a marked decrease in platelet and EMPs. 26 …”