Circulating microparticles are associated with clinical severity of persistent ST-segment elevation myocardial infarction complicated with cardiogenic shock.

BACKGROUND: Cardiogenic shock (CS) is the leading cause of death in patients admitted for acute myocardial infarction (MI). Despite the recent advances in reperfusion and medical treatment mortality remains unacceptably high. Whether cells of the blood compartment in CS-patients are activated and release microparticles (cMPs) that may be both messengers and biomarkers of cell damage is not known. We aimed to investigate the cMP subtypes and parental activated cells of ST-elevation MI (STEMI)-patients complicated by CS and that of non-CS STEMI-patients (non-CS) in order to identify a cMP signature that could aid CS patient's risk stratification. METHODS: Clinically-characterized STEMI-patients with and without CS (36/group) were included. Treatment was delivered according to guidelines and included primary percutaneous coronary intervention. cMPs were characterized by triple-labeling flow cytometry using Annexin V and cell surface-specific monoclonal antibodies. RESULTS: Increased levels of leukocyte-derived (neutrophil and granulocyte origin) and platelet-derived cMPs were detected in CS compared to non-CS patients. A signature of cMPs derived from platelets, leukocytes, and endothelium discriminated CS-patients (AUC of 0.743±0.059 [95% CI: 0.628-0.859], P<0.0001) and predicted mortality in CS (AUC of 0.869±0.06 [95% CI: 0.750-0.988], P<0.0001). In CS-patients, a higher number of platelet- and monocyte-cMPs and of tissue factor-rich cMPs associated to worse myocardial blush grade and thrombolysis in myocardial infarction flow. CONCLUSIONS: cMPs derived from proinflammatory and prothrombotic cells were found to be elevated in CS-patients. In treated as per guidelines CS patients, granulocytes and neutrophils remained activated and actively shed cMPs. These cMPs were biomarkers of adverse prognosis in CS. TRANSLATIONAL ASPECT: Increased levels of leukocyte and platelet-derived circulating microparticles (cMPs) are found in cardiogenic shock (CS) patients as compared to non-CS patients. In CS-patients, a higher number of platelet- and monocyte-cMPs and a higher number of tissue factor-rich cMPs were associated to worse myocardial reperfusion. A specific prothrombotic and proinflammatory cMPs signature in cardiogenic shock (CS) patients is a potential discriminator and survival prognostic biomarker for CS, which could aid management and improve clinical outcomes.

Circulating microparticle signature in coronary and peripheral blood of ST elevation myocardial infarction patients in relation to pain-to-PCI elapsed time.

BACKGROUND: Circulating microparticle (cMP) levels are increased in the acute phase of ST-elevation myocardial infarction (STEMI) and associate with microvascular obstruction; however, the precise cMP-parental cell signature and activation level are not elucidated. Here, we aimed to study the cMP signature in STEMI-patients and whether cMP phenotype changes in relation to onset of pain-to-PCI [ischemic time (IT)]-elapsed time. METHODS: Blood was taken at PCI from the culprit coronary and the peripheral circulation in STEMI-patients (N=40). Two control groups were included: peripheral blood of age-matched patients recovering from STEMI [after 72 h] and of control individuals (N=20/group). cMP-parental origin and activation level were characterized by triple-labeling flow cytometry. RESULTS: Procoagulant annexin V-positive cMPs bearing parental cell markers as well as markers of activated cells displayed a significantly different profile in STEMI-patients, in control individuals and in patients recovering from STEMI. cMPs derived from monocytes, endothelium, and activated vascular cells were higher in the culprit coronary artery than in peripheral blood in STEMI-patients, especially in patients intervened at short IT. Indeed, cMP levels in coronary blood were inversely related to IT duration (more abundant in thrombi with pain-to-PCI time<180 min). CONCLUSIONS: A characteristic [CD66b+/CD62E+/CD142+] cMP signature in the systemic circulation reflects the formation of coronary thrombotic occlusions in STEMI-patients. Changes in the cMP signature in the culprit coronary artery blood reveal the sensitivity of MPs to detect the ischemia-elapsed time. Interestingly, cMPs in peripheral blood may be sensitive markers of the thrombo-occlusive vascular process developing in the coronary arteries of STEMI-patients.

Growing thrombi release increased levels of CD235a(+) microparticles and decreased levels of activated platelet-derived microparticles. Validation in ST-elevation myocardial infarction patients.

BACKGROUND: Local fluid dynamics and exposed atherosclerotic lesions regulate thrombus formation. Activated cells in the attached thrombi release microparticles to the circulation (circulating microparticles [cMPs]); however, their phenotype is unknown. OBJECTIVES: To investigate the specific phenotype of the cMPs released by growing thrombi. METHODS/PATIENTS: cMPs released by thrombi growing in different well-characterized thrombogenic conditions were investigated. cMP contents just before and immediately after perfusion of the thrombogenic surfaces were analyzed by triple-labeling flow cytometry. cMPs were tested for their thrombin-generating capacity. The cMPs identified in the ex vivo perfusion experiments were validated in blood of ST-elevation myocardial infarction (STEMI) patients undergoing thrombectomy and percutaneous coronary intervention. Culprit coronary blood (STEMI-CCB) and peripheral artery blood (STEMI-PAB) were simultaneously analyzed and compared with peripheral artery blood from age-matched controls (C-PAB) and peripheral artery blood from patients who had recovered from acute coronary syndrome (ACS) (pSTEMI-PAB). RESULTS: The levels of annexin V(+) cMPs significantly increased in blood collected after perfusion of the exposed thrombogenic surfaces. cMP release was directly related to the formed thrombus mass and the plasma procoagulant activity. Post-thrombus blood showed higher thrombin generation potential and contained higher levels of cMPs carrying glycophorin-A (CD235a(+) ; erythrocyte-derived microparticles [ErMPs]) than preperfusion blood (P < 0.05), whereas the levels of cMPs carrying activated and adhesion platelet markers were decreased. STEMI-CCB and STEMI-PAB had significantly higher ErMP levels than control blood (P < 0.005). ErMP levels were also significantly higher in STEMI-PAB than in pSTEMI-PAB, validating the experimental mechanistic studies and suggesting that ErMPs are markers of ongoing coronary thrombosis (C-statistics: 0.950; 95% confidence interval 0.889-1.000; P < 0.001). CONCLUSION: Glycophorin-A-rich microparticles are released from evolving growing thrombi into the distal perfusing blood, and can be measured in peripheral blood. CD235a(+) cMPs may constitute a novel systemic biomarker of ongoing thrombosis.