Platelet-, monocyte-derived and tissue factor-carrying circulating microparticles are related to acute myocardial infarction severity

Abstract

Objective: Circulating microparticles (cMPs) are phospholipid-rich vesicles released from cells when activated or injured, and contribute to the formation of intracoronary thrombi. Tissue factor (TF, CD142) is the main trigger of fibrin formation and TF-carrying cMPs are considered one of the most procoagulant cMPs. Similar types of atherosclerotic lesions may lead to different types of AMI, although the mechanisms behind are unresolved. Therefore, we aimed to investigate the phenotype of cMPs found in plasma of ACS patients and its relation to AMI severity and thrombotic burden.

Methods: In a cross-sectional study, two hundred patients aged 75±4 years were included in the study 2-8 weeks after suffering an AMI. Annexin V positive (AV+)-cMPs derived from blood and vascular cells were measured by flow cytometry. Plasma procoagulant activity (TF-PCA) was measured through a chromogenic assay.

Results: STEMI patients (n = 75) showed higher levels of platelet-derived cMPs [CD61+/AV+, CD31+/AV+, CD42b+/AV+ and CD31+/CD42b+/AV+, P = 0.048, 0.038, 0.009 and 0.006, respectively], compared to NSTEMI patients (n = 125). Patients who suffered a heart failure during AMI (n = 17) had increased levels of platelet (CD61+)-and monocyte (CD14+)-derived cMPs carrying TF (CD142+) (P<0.0001 and 0.004, respectively). Additionally, NYHA class III (n = 23) patients showed higher levels of CD142+/AV+, CD14+/AV+ and CD14+/CD142+/AV+ cMPs than those in class I/II (P = 0.001, 0.015 and 0.014, respectively). The levels of these cMPs positively correlated with TF-PCA (r≥0.166, P≤0.027, all).

Conclusions: Platelets and monocytes remain activated in AMI patients treated as per guidelines and release cMPs that discriminate AMI severity. Therefore, TF-MPs, and platelet- and monocyte-MPs may reflect thrombotic burden in AMI patients.

Fig 1. Differences in cMPs between STEMI and NSTEMI patients after 2–8 weeks of suffering an AMI.

Results are expressed as mean + SEM. P values from the differences between STEMI (n = 75) and NSTEMI patients (n = 125, one-way ANOVA). cMPS denote circulating microparticles; STEMI, ST-elevation myocardial infarction; PFP, platelet-free plasma; and AV, Annexin V. A) CD61⁺/AV⁺ cMPs, where CD61 is a biomarker of platelets; B) CD31⁺/AV⁺ cMPs, where CD31 is PECAM (platelet/endothelial cell adhesion molecule 1); C) CD42b⁺/AV⁺ cMPs, where CD42b is von Willebrand factor receptor; and D) CD31⁺/CD42b⁺/AV⁺ cMPs, positive for both CD31 and CD42b.

Fig 2. Differences in cMPs between patients who suffered a HF during the AMI and patients who did not.

Results are expressed as mean + SEM. P values indicate the differences from one-way ANOVA analyses between patients who suffered a HF during the AMI (HF, n = 17) and patients who did not (No-HF, n = 183). cMPS denote circulating microparticles; HF indicates heart failure; AMI, acute myocardial infarction; PFP, platelet-free plasma; and AV,Annexin V. A) CD61⁺/CD142⁺/AV⁺ cMPs, where CD61 is a biomarker of platelets and CD142, tissue factor; B) CD14⁺/AV⁺ cMPs, where CD14 is a biomarker of monocytes; C) CD14⁺/CD11b⁺/AV⁺ cMPs, where CD11b is macrophage-1 antigen (Mac-1); and D) CD14⁺/CD142⁺/AV⁺ cMPs, monocyte-derived cMPs carrying tissue factor.

Fig 3. Differences in cMPs according to the NHYA classification.

Results are expressed as mean + SEM. A) CD142⁺/AV⁺ cMPs, where CD142 is tissue factor; B) CD14⁺/AV⁺ cMPs, where CD14 is a biomarker of monocytes; and C) CD14⁺/CD142⁺/AV⁺ cMPs, monocyte-derived cMPs carrying tissue factor. *Significantly different from class I and II (P = 0.001, 0.015 and 0.014 for CD142⁺/AV⁺, CD14⁺/AV⁺ and CD14⁺/CD142⁺/AV⁺ cMPs respectively, one-way ANOVA with the Bonferroni posthoc test). According to the NHYA classification, 107 patients were allocated at class I, 70 at class II and 23 at class III. cMPs denote circulating microparticles; PFP, platelet-free plasma; and AV, Annexin V.