Dual-specificity phosphatase 3 (DUSP3) is a small phosphatase with poorly known physiological functions and for which only a few substrates are known. Using knockout mice, we recently reported that DUSP3 deficiency confers resistance to endotoxin- and polymicrobial-induced septic shock. We showed that this protection was macrophage dependent. In this study, we further investigated the role of DUSP3 in sepsis tolerance and showed that the resistance is sex dependent. Using adoptive-transfer experiments and ovariectomized mice, we highlighted the role of female sex hormones in the phenotype. Indeed, in ovariectomized females and in male mice, the dominance of M2-like macrophages observed in DUSP3^−/− female mice was reduced, suggesting a role for this cell subset in sepsis tolerance. At the molecular level, DUSP3 deletion was associated with estrogen-dependent decreased phosphorylation of ERK1/2 and Akt in peritoneal macrophages stimulated ex vivo by LPS. Our results demonstrate that estrogens may modulate M2-like responses during endotoxemia in a DUSP3-dependent manner.

Background: Thoracic aortic dissection (TAD) is a life-threatening condition which usually occurs on an aneurysmal aortic wall. Although increasing data have shown that inflammation and oxidative stress play an important role in the patho-physiology of dissection, systemic oxidative stress status (OSS) has not been clearly determined in patients suffering from TAD. Methods: A cohort of 115 patients presenting type A or B TAD were admitted to our center from 2013 to 2017. Out of this cohort, 46 patients were included in a study on dissected aorta (LIege study on DIssected Aorta: LIDIA). In 18 out of the 46 patients, systemic OSS parameters were evaluated after TAD diagnosis by determination of eight different antioxidants, four trace elements, two markers of oxidative lipid damage and two inflammatory markers. Results: The 18 TAD patients included 10 men and 8 women (median age: 62 years; interquartile range: 55–68) diagnosed with type A (N = 8) or B (N = 10) TAD. Low plasma levels of vitamin C, β-carotene, γ-tocopherol, thiol proteins, paraoxonase and selenium were observed in these 18 patients. By contrast, the concentration of copper and total hydroperoxides, copper/zinc ratio, as well as inflammatory markers, were higher than the reference intervals. No difference was observed in oxidative stress biomarker concentrations between type A and B TAD patients. Conclusions: This pilot study, limited to 18 TAD patients, revealed a heightened systemic OSS, determined at 15.5 days (median) after the initial diagnosis, in those TAD patients without complications (malperfusion syndrome and aneurysm formation). Larger studies on biological fluids are needed to better characterize the oxidative stress and interpret its consequence in TAD disease.

Background: Abdominal aortic aneurysm (AAA) is a life-threatening condition due to the risk of aneurysm growth and rupture. Biomarkers linked to AAA pathogenesis are attractive candidates for AAA diagnosis and prognosis. The aim of this study was to assess circulating biomarkers levels relationship with PET imaging positivity and their predictive value in AAA growth rate. Methods: A total of 164 patients with AAA had whole body [¹⁸F]FDG PET/CT examination and blood drawn for biomarkers analysis at inclusion. Of these, 121 patients had at least one follow-up imaging assessment for AAA progression. Median (quartiles) imaging follow-up period was 32.8 months (15.2–69.6 months). Results: At baseline, PET was visually positive in 28 (17%) patients. Among PET+ patients, female proportion was higher compared to PET−patients (respectively, n = 6, 21.4% vs. n = 11, 8.1%, p = 0.046). Biomarkers of inflammation (CRP, CCL18), of proteolytic activity (MMP9), of extracellular matrix, and calcification regulation (OPN, OPG) were all significantly increased in PET+ patients (p < 0.05). During follow-up, rapid AAA growth (increase in size ≥ 1 cm per year) was observed in 36 (29.8%) patients and several biomarkers (CRP, MMP9, OPN, and OPG) were increased in those patients compared to patients without rapid growth (p < 0.05). Conclusions: Although PET positivity at baseline was not associated with rapid growth, CRP levels showed a significant association.

Pharmacotherapy for abdominal aortic aneurysm (AAA) can be useful for prevention, especially in people at higher risk, for slowing down AAA progression, as well as for post-surgery adjuvant treatment. Our review focuses on novel pharmacotherapy approaches targeted towards slowing down progression of AAA, known also as secondary prevention therapy. Guidelines for AAA are not specific to slow down the expansion rate of an abdominal aortic aneurysm, and therefore no medical therapy is recommended. New ideas are urgently needed to develop a novel medical therapy. We are hopeful that in the future, pharmacologic treatment will play a key role in the prevention and treatment of AAA.

Background: Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease that poses several challenges. Given the increasing evidence that AAA patients are more likely to develop cancer and the importance of its early detection, we strived to develop a non-invasive tool based on serial FDG-PET/CT scan examinations to identify, among AAA patients, those at risk of cancer. Methods: Between 2006 and 2011 we recruited 149 AAA patients, free of cancer at baseline, and followed them until the end of 2021. All patients underwent an FDG-PET/CT scan at inclusion and possibly more scans during follow-up. At each medical imaging examination, the aneurysmal FDG uptake was recorded. Patients were stratified based on their aortic wall PET status (negative/positive). Any occurrence of cancer was reported. A Cox regression analysis and competing-risk modeling were applied to the data. Results: The proportion of AAA patients who developed cancer was 31.5% (mean time to diagnosis was 5.7 ± 3.4 years) and the death rate was 59%. A difference in cancer incidence between PET+ and PET− patients was detected (46.8% vs. 27.3%; HR = 1.96, 95%CI: 1.07–3.57, p = 0.028). Moreover, AAA patients undergoing surgical treatment had a lower risk of cancer than unoperated patients (28% vs. 50%; HR = 0.41, 95%CI: 0.21–0.80, p = 0.009). Conclusions: In AAA patients, diagnostic imaging with an FDG-PET/CT scan can help identify those patients at a higher risk of developing cancer. Moreover, the higher cancer risk in non-surgically treated patients calls for further analysis of associations between aneurysm growth and malignant disease.