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Endothelial progenitor cells (EPCs) are a heterogeneous group of cells present in peripheral blood at various stages of endothelial differentiation. EPCs have been extensively investigated in patients with coronary artery disease (CAD), with controversial findings both on their role in atherosclerosis progression and in the process of neointimal growth after a percutaneous coronary intervention (PCI). Despite nearly 2 decades of experimental and clinical investigations, however, the significance of EPCs in clinical practice remains unclear and poorly understood. This review provides an update on the role of EPCs in the most common clinical scenarios that are experienced by cardiologists managing patients with CAD. We here summarize the main findings on the association of EPCs with cardiovascular risk factors, coronary atherosclerosis, and myocardial ischemia. We then discuss the potential effects of EPCs in post-PCI in-stent restenosis, as well as most recent findings with EPC-coated stents. Based on the mounting evidence of the relationship between levels of EPCs and several different adverse cardiovascular events, EPCs are emerging as novel predictive biomarkers of long-term outcomes in patients with CAD., (© The Author(s) 2022. Published by Oxford University Press.)

Aims: Strong epidemiologic evidence has highlighted the role of pollution, on top of adverse climate features, as a novel cardiovascular risk factor. However, mechanistic proof that reducing pollution may be beneficial to prevent atherothrombotic events is limited. We aimed at appraising the impact of temporary traffic bans in a large metropolitan area on the risk of acute coronary syndromes., Methods and Results: Aggregate and anonymized data from 15 tertiary cardiac care centers were obtained detailing pre-coronarivus disease 2019 (COVID-19) daily cases of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), including those treated with percutaneous coronary intervention (PCI). Data on pollutants and climate were sought for the same days. Mixed level regression was used to compare the week before vs. after the traffic ban (Fortnight analysis), the 3 days before vs. after (Weekly analysis) and the Sunday before vs. after (Sunday analysis). A total of 8 days of temporary traffic bans were included, occurring between 2017 and 2020, totaling 802 STEMI and 1196 NSTEMI in the Fortnight analysis, 382 STEMI and 585 in the Weekly analysis, and 148 STEMI and 210 NSTEMI in the Sunday analysis. Fortnight and Sunday analysis did not disclose a significant impact of traffic ban on STEMI or NSTEMI (all P  > 0.05). Conversely, Weekly analysis showed non-significant changes for STEMI but a significant decrease in daily NSTEMI when comparing the 3 days before the traffic ban with the ban day ( P  = 0.043), as well as the 3 days before vs. the 3 days after the ban ( P  = 0.025). No statistically significant effect of traffic ban was found at Fortnight, Weekly or Sunday analyses for daily mean concentrations of benzene, carbon monoxide, nitric oxide, nitrogen dioxide, ozone, sulfur dioxide, particulate matter (PM) <2.5 µm or PM < 10 µm (all P  > 0.05). However, minimum daily concentrations showed a significant reduction of ozone during the ban in comparison to the week preceding it ( P  = 0.034), nitric oxide during the ban in comparison to the 3 days preceding it ( P  = 0.046), and an increase in benzene during the ban in comparison to the Sunday before ( P  = 0.039)., Conclusion: Temporary traffic bans may favorably reduce coronary atherothrombotic events, and in particular NSTEMI, even if not globally and immediately impacting on environmental pollution. Further controlled studies are required to confirm and expand this hypothesis-generating results., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions please email: journals.permissions@oup.com.)

Aims: Low-grade endotoxaemia is detectable in human circulation but its role in thrombosis is still unclear., Methods and Results: We measured serum lipopolysaccharide (LPS) concentration, soluble P-selectin (sP-selectin), a marker of platelet activation, and zonulin, a marker of gut permeability, in peripheral circulation, coronary thrombi, and intracoronary blood of patients with ST-elevation myocardial infarction (STEMI, n = 50) and stable angina (SA) (n = 50), respectively, and in controls (n = 50). Experimental study was carried out in mice to assess if Escherichia coli-LPS (E. coli-LPS) possess thrombotic property. Coronary thrombi from STEMI showed higher concentrations of LPS, sP-selectin vs. intracoronary blood of SA and peripheral blood of controls (P < 0.001). Zonulin was higher in STEMI compared to the other two groups [4.57 (3.34-5.22); 2.56 (0.41-4.36); 1.95 (1.22-2.65) ng/mL; P < 0.001] and correlated with LPS (Rs = 0.585; P < 0.001). Escherichia coli DNA was positive in 34% of STEMI vs. 12% of SA and 4% of controls (P < 0.001). In a subgroup of 12 STEMI, immunohistochemical analysis of coronary thrombi showed positivity for leucocyte Toll-like receptor 4 (TLR4), cathepsin G, and LPS from E. coli in 100%, 80%, and 25% of samples, respectively. E. coli-LPS injected in mice to reach LPS concentrations like those detected in coronary thrombi was associated with enhanced artery thrombosis and platelet activation, an effect blunted by TLR4 inhibitor co-administration. In vitro study demonstrated that LPS from E. coli enhanced platelet aggregation via TLR4-mediated leucocyte cathepsin G activation., Conclusion: ST-elevation myocardial infarction patients disclose an enhanced gut permeability that results in LPS translocation in human circulation and eventually thrombus growth at site of artery lesion via leucocyte-platelet interaction., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: Percutaneous closure of patent foramen ovale (PFO) in cryptogenic cerebrovascular events is an alternative to medical therapy. The interpretation of residual shunts after implantation of different devices for PFO with different morphologies is controversial., Methods and Results: Transcatheter PFO closure was performed in 123 patients with a history of ≥1 paradoxical embolism using three different devices: Amplatzer (n = 46), Figulla Occlutech (n = 41), and Atriasept Cardia (n = 36). Fifty-six patients presented with simple PFO and 67 patients had complex morphologies. All patients were studied with contrast enhanced transesophageal echocardiography (TEE) before interventional procedure and thereafter at 1 and 6 months and every 6-12 months in case of incomplete closure. Definite closure was confirmed in at least two consecutive TEE studies. Various PFO morphologies were identified by TEE before device implantation. The device size to PFO diameter ratio was significantly increased in patients with complex PFO compared with those patients with a simple PFO morphology (P < 0.05). The difference between the closure rate of S-PFO and C-PFO concerning each device type was significant (Amplatzer P = 0.0027, Figulla P = 0.0043, and Atriasept P < 0.01). The mean follow-up period was 3.4 years (median 2.7 years) with a cerebrovascular re-event rate of 2.4% per year. In three patients, thrombi were detected in the 6-month TEE controls and resolved after medical therapy. In three other patients, the implantation of an adjunctive device was necessary for residual shunt., Conclusion: In our series of patients, the closure rate was dependent on PFO morphology more than occluder size and type. An adjunctive device was implanted in selected cases., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)