Context-dependent regulation of endothelial cell metabolism: differential effects of the PPARβ/δ agonist GW0742 and VEGF-A

Peroxisome proliferator activated receptor β/δ (PPARβ/δ) has pro-angiogenic functions, but whether PPARβ/δ modulates endothelial cell metabolism to support the dynamic phenotype remains to be established. This study characterised the metabolic response of HUVEC to the PPARβ/δ agonist, GW0742, and compared these effects with those induced by VEGF-A. In HUVEC monolayers, flux analysis revealed that VEGF-A promoted glycolysis at the expense of fatty acid oxidation (FAO), whereas GW0742 reduced both glycolysis and FAO. Only VEGF-A stimulated HUVEC migration and proliferation whereas both GW0742 and VEGF-A promoted tubulogenesis. Studies using inhibitors of PPARβ/δ or sirtuin-1 showed that the tubulogenic effect of GW0742, but not VEGF-A, was PPARβ/δ- and sirtuin-1-dependent. HUVEC were reliant on glycolysis and FAO, and inhibition of either pathway disrupted cell growth and proliferation. VEGF-A was a potent inducer of glycolysis in tubulogenic HUVEC, while FAO was maintained. In contrast, GW0742-induced tubulogenesis was associated with enhanced FAO and a modest increase in glycolysis. These novel data reveal a context-dependent regulation of endothelial metabolism by GW0742, where metabolic activity is reduced in monolayers but enhanced during tubulogenesis. These findings expand our understanding of PPARβ/δ in the endothelium and support the targeting of PPARβ/δ in regulating EC behaviour and boosting tissue maintenance and repair

How do cardiologists select patients for dual antiplatelet therapy continuation beyond 1 year after a myocardial infarction? Insights from the EYESHOT Post-MI Study

Background: Current guidelines suggest to consider dual antiplatelet therapy (DAPT) continuation for longer than 12 months in selected patients with myocardial infarction (MI). Hypothesis: We sought to assess the criteria used by cardiologists in daily practice to select patients with a history of MI eligible for DAPT continuation beyond 1 year. Methods: We analyzed data from the EYESHOT Post-MI, a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. Results: Out of the 1633 post-MI patients enrolled in the study between March and December 2017, 557 (34.1%) were on DAPT at the time of enrolment, and 450 (27.6%) were prescribed DAPT after cardiologist assessment. At multivariate analyses, a percutaneous coronary intervention (PCI) with multiple stents and the presence of peripheral artery disease (PAD) resulted as independent predictors of DAPT continuation, while atrial fibrillation was the only independent predictor of DAPT interruption for patients both at the second and the third year from MI at enrolment and the time of discharge/end of the visit. Conclusions: Risk scores recommended by current guidelines for guiding decisions on DAPT duration are underused and misused in clinical practice. A PCI with multiple stents and a history of PAD resulted as the clinical variables more frequently associated with DAPT continuation beyond 1 year from the index MI

Spontaneous pneumomediastinum and pneumothorax in nonintubated COVID-19 patients: A multicenter case series

Objective: Rare coexistence of disease or pathology Background: COVID-19 caused by SARS-CoV-2 has become a global pandemic. Diagnosis is based on clinical features, nasopharyngeal swab analyzed with real-time reverse transcription-polymerase chain reaction, and computer tomography (CT) scan pathognomonic signs. The most common symptoms associated with COVID-19 include fever, coughing, and dyspnea. The main complications are acute respiratory distress syndrome, pneumonia, kidney failure, bacterial superinfections, coagulation abnormalities with thromboembolic events, sepsis, and even death. The common CT manifestations of COVID-19 are ground-glass opacities with reticular opacities and consolidations. Bilateral lung involvement can be present, especially in the posterior parts and peripheral areas. Pleural effusion, pericardial effusion, and lymphadenopathy are rarely described. Spontaneous pneumothorax and pneumomediastinum have been observed as complications in patients with SARS-CoV-2 pneumonia during mechanical ventilation or noninvasive positive pressure ventilation, as well as in patients with spontaneous breathing receiving only oxygen therapy via nasal cannula or masks. Case Reports: We present 2 cases of pneumomediastinum with and without pneumothorax in patients with active SARS-Cov-2 infection and 1 case of spontaneous pneumothorax in a patient with a history of paucisymptomatic SARS-CoV-2 infection. In these 3 male patients, ages 78, 73, and 70 years, respectively, COVID-19 was diagnosed through nasopharyngeal sampling tests and the presence of acute respiratory distress syndrome. Conclusions: Both pneumothorax and pneumomediastinum, although rare, may be complications during or after SARS-CoV-2 infection even in patients who are spontaneously breathing. The aim of this study was to describe an increasingly frequent event whose early recognition can modify the prognosis of patients