Disruption of the intercellular interactions between endothelial cells leads to endothelial dysfunction. The role of nanoparticles in plasma membrane stability, actin cytoskeleton organization and intercellular junctions is unclear. Human umbilical vein endothelial cells were treated with zinc oxide NPs in vitro. Cell shape, adhesiveness and plasma membrane integrity were analyzed by means of optical fluorescence microscopy, scanning electron microscopy and flow cytometry methods. Additionally, lactate dehydrogenase activity assay and annexin V staining were performed. The scanning electron microscopy analysis showed changes in morphology and surface topography. The F-actin organization was typical for migrating cells. Cell membrane damage (significant increase in lactate dehydrogenase release and annexin V staining) was observed in the concentration of ZnO nanoparticles above 30 μg/ml. The relationship between ZnO nanoparticles and endothelial dysfunction was clearly established and the importance of cytoskeleton reorganization and loosening of the continuous endothelial monolayer after nanoparticles exposure has been documented.

Background: Type 2 diabetes mellitus (T2DM) patients are at high risk of cardiovascular (CV) events. Factor XI (FXI) is associated with arterial thromboembolism, including myocardial infarction (MI), stroke, and CV mortality. The role of FXI in T2DM is unknown. We investigated whether plasma FXI is associated with CV events in T2DM patients in long-term observation. Methods: In 133 T2DM patients (aged 66 ± 8 years, 40.6% women, median T2DM duration 5 [2–10] years) we assessed plasma FXI levels, along with fibrin clot properties, thrombin generation, and fibrinolysis proteins. A composite endpoint of MI, stroke, or CV death, as well as CV mortality alone were assessed during a median follow-up of 72 months. Results: Plasma FXI above the 120% upper normal limit was detected in 25 (18.8%) patients and showed positive association with LDL cholesterol and thrombin activatable fibrinolysis inhibitor, but not glycated hemoglobin, inflammatory markers or thrombin generation. The composite endpoint (n = 21, 15.8%) and CV death alone (n = 16, 12%) were more common in patients with elevated FXI (hazard ratio [HR] 10.94, 95% confidence interval [CI] 4.46–26.87, p < 0.001 and HR 7.11, 95% CI 2.61–19.31, p < 0.001, respectively). On multivariable analysis, FXI remained an independent predictor of the composite endpoint and CV death, regardless of concomitant coronary artery disease. Conclusions: To our knowledge, this study is the first to show that in T2DM patients, elevated FXI could predict major CV events, including mortality, which suggest that anti-FXI agents might be a potential novel antithrombotic option in this disease.

Atherosclerosis remains a large health and economic burden. Even though it has been studied for more than a century, its complex pathophysiology has not been elucidated. The relatively well-established contributors include: chronic inflammation in response to oxidized cholesterol, reactive oxygen species-induced damage and apoptosis. Recently, profilin 1, a regulator of actin dynamics emerged as a potential new player in the field. Profilin is abundant in stable atherosclerotic plaques and in thrombi extracted from infarct-related arteries in patients with acute myocardial infarction. The exact role of profilin in atherosclerosis and its complications, as well as its mechanisms of action, remain unknown. Here, we summarize several pathways in which profilin may act through mitochondria in a number of processes implicated in atherosclerosis.

There is a discrepancy between epicardial vessel patency and microcirculation perfusion in a third of patients treated with percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Optimization with aspiration thrombectomy (AT) may reduce distal embolization and microvascular obstruction. The effect of AT in the treatment of STEMI is debatable. The purpose of this study was to use cardiac magnetic resonance (CMR) to determine whether AT influences microvascular obstruction (MVO), infarct size and left ventricular (LV) remodelling in STEMI patients. Sixty STEMI patients with a thrombus-occluded coronary artery were randomized in a 2:1 fashion to receive PCI proceeded by AT (AT + PCI group), or PCI only. MVO, myocardial infarct size and LV remodelling were assessed by CMR during the index hospitalization and 6 months thereafter. The majority of patients had a large thrombus burden (TIMI thrombus grade 5 in over 70% of patients). PCI and AT were effective in all cases. There were no periprocedural strokes. CMR showed that the addition of AT to standard PCI was associated with lesser MVO when indexed to the infarct size and larger infarct size reduction. There were less patients with left ventricle remodelling in the AT + PCI vs. the PCI only group. To conclude, in STEMI patients with a high thrombus burden, AT added to PCI is effective in reducing infarct size, MVO and LV remodelling.