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.

Allelic diversity and affinity variants of MICA are imbalanced in Spanish patients with Behçet's disease.

The aetiology of Behçet's disease (BD) is still unknown, but genetic and environmental factors are involved. HLA-B*51 is considered a susceptibility marker and some MICA alleles have also been associated. Cytotoxic T lymphocytes have been suggested as responsible for BD lesions by engaging MICA through NKG2D surface molecules. In the present study, HLA-B and MICA alleles were typed by polymerase chain reaction using sequence-specific primers, in 165 healthy Spanish controls and 42 BD patients. In the healthy group, MICA*008 (28.48%), MICA*004 (17.58%), MICA*002 (14.24%) and MICA*009 (9.39%) were the predominant alleles and the most common haplotype was MICA*004-B*44 (12.12%). MICA*001 (5.15%), MICA*004, MICA*011 (4.54%) and MICA*018 (5.15%) were more frequent, and MICA*010 (1.81%) and MICA*008 were less prevalent than in other Caucasoid populations. Similar results have been reported in North African individuals and this could support the hypothesis of a common ancestral origin of both populations. The frequencies of MICA*009 and MICA*019 were significantly increased in our BD patients in comparison with controls: 22.62% versus 9.39% and 10.71% versus 1.81% respectively. The increase of MICA*019 had not been described in other BD cohorts, and it corroborates the genetic heterogeneity at MICA locus in BD patients. High-affinity MICA alleles for NKG2D were more frequent in controls than in patients. Moreover, high-affinity alleles were not found in homozygous BD patients. These results argue against the hypothesis of an autoaggressive response in BD patients through MICA-NKG2D interactions.