Giulio Accarino

BACKGROUND: Microplastics and nanoplastics (MNPs) are emerging as a potential risk factor for cardiovascular disease in preclinical studies. Direct evidence that this risk extends to humans is lacking. METHODS: We conducted a prospective, multicenter, observational study involving patients who were undergoing carotid endarterectomy for asymptomatic carotid artery disease. The excised carotid plaque specimens were analyzed for the presence of MNPs with the use of pyrolysis-gas chromatography-mass spectrometry, stable isotope analysis, and electron microscopy. Inflammatory biomarkers were assessed with enzyme-linked immunosorbent assay and immunohistochemical assay. The primary end point was a composite of myocardial infarction, stroke, or death from any cause among patients who had evidence of MNPs in plaque as compared with patients with plaque that showed no evidence of MNPs. RESULTS: A total of 304 patients were enrolled in the study, and 257 completed a mean (±SD) follow-up of 33.7±6.9 months. Polyethylene was detected in carotid artery plaque of 150 patients (58.4%), with a mean level of 21.7±24.5 μg per milligram of plaque; 31 patients (12.1%) also had measurable amounts of polyvinyl chloride, with a mean level of 5.2±2.4 μg per milligram of plaque. Electron microscopy revealed visible, jagged-edged foreign particles among plaque macrophages and scattered in the external debris. Radiographic examination showed that some of these particles included chlorine. Patients in whom MNPs were detected within the atheroma were at higher risk for a primary end-point event than those in whom these substances were not detected (hazard ratio, 4.53; 95% confidence interval, 2.00 to 10.27; P<0.001). CONCLUSIONS: In this study, patients with carotid artery plaque in which MNPs were detected had a higher risk of a composite of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than those in whom MNPs were not detected. (Funded by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale and others; ClinicalTrials.gov number, NCT05900947.).

AIMS: Here, we aimed to determine the therapeutic effect of longevity-associated variant (LAV)-BPIFB4 gene therapy on atherosclerosis. METHODS AND RESULTS: ApoE knockout mice (ApoE-/-) fed a high-fat diet were randomly allocated to receive LAV-BPIFB4, wild-type (WT)-BPIFB4, or empty vector via adeno-associated viral vector injection. The primary endpoints of the study were to assess (i) vascular reactivity and (ii) atherosclerotic disease severity, by Echo-Doppler imaging, histology and ultrastructural analysis. Moreover, we assessed the capacity of the LAV-BPIFB4 protein to shift monocyte-derived macrophages of atherosclerotic mice and patients towards an anti-inflammatory phenotype. LAV-BPIFB4 gene therapy rescued endothelial function of mesenteric and femoral arteries from ApoE-/- mice; this effect was blunted by AMD3100, a CXC chemokine receptor type 4 (CXCR4) inhibitor. LAV-BPIFB4-treated mice showed a CXCR4-mediated shift in the balance between Ly6Chigh/Ly6Clow monocytes and M2/M1 macrophages, along with decreased T cell proliferation and elevated circulating levels of interleukins IL-23 and IL-27. In vitro conditioning with LAV-BPIFB4 protein of macrophages from atherosclerotic patients resulted in a CXCR4-dependent M2 polarization phenotype. Furthermore, LAV-BPIFB4 treatment of arteries explanted from atherosclerotic patients increased the release of atheroprotective IL-33, while inhibiting the release of pro-inflammatory IL-1β, inducing endothelial nitric oxide synthase phosphorylation and restoring endothelial function. Finally, significantly lower plasma BPIFB4 was detected in patients with pathological carotid stenosis (>25%) and intima media thickness >2 mm. CONCLUSION: Transfer of the LAV of BPIFB4 reduces the atherogenic process and skews macrophages towards an M2-resolving phenotype through modulation of CXCR4, thus opening up novel therapeutic possibilities in cardiovascular disease.

An abdominal aortic aneurysm (AAA) is a degenerative pathology that affects the infrarenal segment of the aorta, leading to its progressive dilatation and eventually rupture. The infrarenal segment is involved in 80% of the aortic aneurisms, and represents alone 30% of all aneurysms. The natural history of the disease is characterized by the progressive increase of the aortic diameter associated with proportionally higher risk of rupture, particularly for cases with diameter greater than 5.5 cm. In case of rupture the mortality rate is very high, independently from the endovascular or surgical treatment. The most important risk factors are older age, smoking, hypertension, dyslipidemia, and family history of AAA. The most frequent form is "atherosclerotic", but infectious, collagen disease-related, immune dysregulation-related, and post-traumatic AAA have also been described. Albeit multiple pathogenetic hypotheses have been proposed, the role of metallo-proteinases in the degeneration of the aortic wall seem to play a central role. Early detection of AAA is crucial for the identification and treatment before the onset of potentially life-threatening complications. Moreover, the individual risk stratification is fundamental for the clinical management and follow-up. The growing knowledge about the pathophysiology of AAA has the potential to lead to significant translational advances. The challenge for the next years is to employ bioinformatic and genetic models, also based on artificial intelligence and machine learning approach, to develop novel screening methods and to stratify individuals at higher-risk or in the early stages of AAA.

OBJECTIVES: To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on acute and elective thoracic and abdominal aortic procedures. METHODS: Forty departments shared their data on acute and elective thoracic and abdominal aortic procedures between January and May 2020 and January and May 2019 in Europe, Asia and the USA. Admission rates as well as delay from onset of symptoms to referral were compared. RESULTS: No differences in the number of acute thoracic and abdominal aortic procedures were observed between 2020 and the reference period in 2019 [incidence rates ratio (IRR): 0.96, confidence interval (CI) 0.89-1.04; P = 0.39]. Also, no difference in the time interval from acute onset of symptoms to referral was recorded (<12 h 32% vs > 12 h 68% in 2020, < 12 h 34% vs > 12 h 66% in 2019 P = 0.29). Conversely, a decline of 35% in elective procedures was seen (IRR: 0.81, CI 0.76-0.87; P < 0.001) with substantial differences between countries and the most pronounced decline in Italy (-40%, P < 0.001). Interestingly, in Switzerland, an increase in the number of elective cases was observed (+35%, P = 0.02). CONCLUSIONS: There was no change in the number of acute thoracic and abdominal aortic cases and procedures during the initial wave of the COVID-19 pandemic, whereas the case load of elective operations and procedures decreased significantly. Patients with acute aortic syndromes presented despite COVID-19 and were managed according to current guidelines. Further analysis is required to prove that deferral of elective cases had no impact on premature mortality.

BACKGROUND: Arterial diseases like coronary artery disease (CAD), carotid stenosis (CS), peripheral artery disease (PAD), and abdominal aortic aneurysm (AAA) have high morbidity and mortality, making them key research areas. Their multifactorial nature complicates patient treatment and prevention. Biomarkers offer insights into the biochemical and molecular processes, while social factors also significantly impact patients' health and quality of life. This scoping review aims to search the literature for studies that have linked the biological mechanisms of arterial diseases through biomarkers with social issues and to analyze them, supporting the interdependence of biological and social sciences. METHODS: After a rigorous selection process, adhering to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for Scoping Reviews, 30 articles were identified through Scopus, Web of Science, and PubMed. Inclusion and exclusion criteria were based on the population, intervention, comparator, outcome, time, and setting framework. Inclusion criteria were studies involving human subjects that explored the relationships among arterial diseases, biomarkers, and psychosocial factors, with no restrictions on publication date. Nonhuman studies, purely biological or medical analyses without psychosocial dimensions, and non-English publications were excluded. Eligible study types included experimental, observational, and review articles published in peer-reviewed journals. Data extraction focused on study characteristics, such as authors, publication year, country, methods, population, and findings. Results were synthesized narratively, as this format was deemed the most suitable for summarizing diverse findings. The quality or methodological rigor of the included studies was not formally assessed, consistent with the scoping review methodology. RESULTS: In CAD, biomarkers such as high-sensitivity C-reactive protein are strongly associated with psychological stress, whereas lipoprotein (a) and the apolipoprotein B/apolipoprotein A1 ratio reflect lipid profiles that are influenced by socioeconomic factors and ethnicity. In CS, increased carotid intima-media thickness is linked to psychiatric conditions like attention deficit/hyperactivity disorder, and heat shock protein-70 levels are associated with socioeconomic status and gender. In PAD, inflammatory markers, including interleukin-6, intracellular adhesion molecule-1, and high-sensitivity C-reactive protein, mediate the connection between depression and disease severity, with gender and ethnicity influencing the expression of biomarkers and clinical outcomes. In AAA, factors like smoking and exposure to air pollution have increased matrix metalloproteinase levels and other inflammatory markers. Additionally, estradiol provides partial protection in women, underscoring the role of hormones and environmental influences in disease progression. Social determinants such as socioeconomic status, healthcare access, and ethnicity significantly affect biomarker levels and arterial disease progression. CONCLUSIONS: These findings are crucial for the assumption that social determinants of health modulate the levels of inflammatory biomarkers involved in the progression of arterial diseases such as CAD, CS, PAD, and AAA. This highlights the need to integrate highly predictive mathematical systems into clinical practice, combining biological sciences with social sciences to achieve advanced standards in precision medicine. However, further studies are needed to validate these approaches fully.