Reactive oxygen species (ROS) induce nuclear factor erythroid 2–related factor 2 (Nrf2) activation as an adaptive defense mechanism, determining the synthesis of antioxidant molecules, including heme-oxygenase-1 (HO-1). HO-1 protects cells against oxidative injury, degrading free heme and inhibiting ROS production. HO-1 is highly expressed in macrophages during plaque growth. Macrophages are morpho-functionally heterogeneous, and the prevalence of a specific phenotype may influence the plaque fate. This heterogeneity has also been observed in monocyte-derived macrophages (MDMs), a model of macrophages infiltrating tissue. The study aims to assess oxidative stress status and Nrf2/HO-1 axis in MDM morphotypes obtained from healthy subjects and coronary artery disease (CAD) patients, in relation to coronary plaque features evaluated in vivo by optical coherence tomography (OCT). We found that MDMs of healthy subjects exhibited a lower oxidative stress status, lower Nrf2 and HO-1 levels as compared to CAD patients. High HO-1 levels in MDMs were associated with the presence of a higher macrophage content, a thinner fibrous cap, and a ruptured plaque with thrombus formation, detected by OCT analysis. These findings suggest the presence of a relationship between in vivo plaque characteristics and in vitro MDM profile, and may help to identify patients with rupture-prone coronary plaque.

Cytotoxin-associated gene antigen (CagA)-positive strains of Helicobacter pylori have previously been associated with acute coronary syndromes. However, the role of CagA-positive strains of Helicobacter pylori in recurring cardiac events after ST-segment elevation myocardial infarction (STEMI) has not yet been assessed. We enrolled 181 consecutive patients (155 men, mean age 64±13 years) presenting with STEMI. In all patients, serum levels of IgG anti-CagA were assessed. Levels of IgG anti-hepatitis A virus were also evaluated in all patients in order to exclude the presence of a bystander activation of the immune system. Finally, a previous history of acute coronary syndrome and the rate of major adverse cardiovascular events as a composite of cardiovascular death, recurring myocardial infarction and target lesion revascularisation within 2 years follow-up were evaluated. Anti-CagA IgG seropositive patients presented more frequently with a previous history of acute coronary syndrome compared with seronegative patients (28.3% vs. 14%, P=0.019). Interestingly, no differences were observed between anti-CagA IgG seropositive and anti-CagA IgG seronegative patients concerning the prevalence of anti-hepatitis A virus IgG seropositivity (20% vs. 21.4%, P=0.48). At 2-year follow-up, 40 patients experienced major adverse cardiovascular events. The major adverse cardiovascular event rate was higher in anti-CagA IgG seropositive compared with seronegative patients (hazard ratio 2.25, 95% confidence interval 1.34–2.95, P=0.013), which was confirmed at Cox multivariate analysis (hazard ratio 2.33, 95% confidence interval 1.30–3.14, P=0.009). CagA-positive strains of Helicobacter pylori seem to be involved in the pathogenesis of recurring acute coronary syndromes, and seropositivity for anti-CagA IgG predicts prognosis after STEMI, possibly due to the increased risk of recurring cardiac events.

Netrin-1 is a laminin-like protein that plays a pivotal role in cell migration and, according to the site of its release, exerts both pro and anti-atherosclerotic functions. Macrophages, key cells in atherosclerosis, are heterogeneous in morphology and function and different subpopulations may support plaque progression, stabilization, and/or regression. Netrin-1 was evaluated in plasma and, together with its receptor UNC5b, in both spindle and round monocyte-derived macrophages (MDMs) morphotypes from coronary artery disease (CAD) patients and control subjects. In CAD patients, plaque features were detected in vivo by optical coherence tomography. CAD patients had lower plasma Netrin-1 levels and a higher MDMs expression of both protein and its receptor compared to controls. Specifically, a progressive increase in Netrin-1 and UNC5b was evidenced going from controls to stable angina (SA) and acute myocardial infarction (AMI) patients. Of note, spindle MDMs of AMI showed a marked increase of both Netrin-1 and its receptor compared to spindle MDMs of controls. UNC5b expression is always higher in spindle compared to round MDMs, regardless of the subgroup. Finally, CAD patients with higher intracellular Netrin-1 levels showed greater intraplaque macrophage accumulation in vivo. Our findings support the role of Netrin-1 and UNC5b in the atherosclerotic process.

Coronary artery disease (CAD) patients are at high ischemic risk, and new biomarkers reflecting atherosclerotic disease severity and coronary plaque vulnerability are required. The Brain-Derived Neurotrophic Factor (BDNF) affects endothelial and macrophage activation suggesting its involvement in atherosclerotic plaque behavior. To investigate whether plasma BDNF is associated with in vivo coronary plaque features, assessed by optical coherence tomography (OCT), in both acute myocardial infarction (AMI) and stable angina (SA) patients, we enrolled 55 CAD patients (31 SA and 24 AMI), and 21 healthy subjects (HS). BDNF was lower in CAD patients than in HS (p < 0.0001), and it decreased with the presence, clinical acuity and severity of CAD. The greater BDNF levels were associated with OCT features of plaque vulnerability in overall CAD as well as in SA and AMI patients (p < 0.03). Specifically, in SA patients, BDNF correlated positively with macrophages’ infiltration within atherosclerotic plaque (p = 0.01) and inversely with minimal lumen area (p = 0.02). In AMI patients a negative correlation between BDNF and cap thickness was found (p = 0.02). Despite a small study population, our data suggest a relationship between BDNF and coronary plaque vulnerability, showing that vulnerable plaque is positively associated with plasma BDNF levels, regardless of the clinical CAD manifestation.

Low‐cost, millimeter‐thick chitosan‐based sponges are engineered with zinc oxide (ZnO) using atomic layer deposition (ALD) to create a multifunctional nanocomposite for the potential application in water remediation and self‐regeneration via solid‐state photocatalysis. Initially, non‐porous chitosan films served as control samples to study the ZnO growth mechanism and its impact on the biopolymer's optical and chemical properties. Subsequently, porous chitosan sponges are engineered to further explore the photocatalyst growth and infiltration into the porous matrix. The characterization of the chitosan/ZnO hybrid material is performed using spectroscopic ellipsometry, X‐ray photoelectron spectroscopy, UV–vis, photoluminescence, and infrared spectroscopy, analyzing the effect of varying the number of ALD cycles, resulting in different ZnO thicknesses in the range of 5–30 nm on the chitosan matrix. A reaction‐limited growth model is found and strong interactions between ZnO and chitosan amino groups significantly enhance the stability in water and impart photocatalytic features. Adsorption tests using Direct Blue 78 dye demonstrated high removal efficiency, with capacities up to 2000 mg g⁻¹, surpassing pristine chitosan sponges, which degrade in water. Electrostatic interactions between dye sulfonate groups and protonated chitosan amino moieties are identified as key to this performance. Preliminary photocatalytic experiments using Naproxen confirms the ZnO‐coated sponges' ability to degrade pollutants, showcasing ALD as a key technology for producing bio‐based, photoactive materials for sustainable water treatment.