Resveratrol Improves Endothelial Function by A PREP1-Mediated Pathway in Mouse Aortic Endothelial Cells.

PREP1 is a homeodomain transcription factor that impairs metabolism and is involved in age-related aortic thickening. In this study, we evaluated the role of PREP1 on endothelial function. Mouse Aortic Endothelial Cells (MAECs) transiently transfected with a Prep1 cDNA showed a 1.5- and 1.6-fold increase in eNOSThr495 and PKCα phosphorylation, respectively. Proinflammatory cytokines Tnf-α and Il-6 increased by 3.5 and 2.3-fold, respectively, in the presence of Prep1, while the antioxidant genes Sod2 and Atf4 were significantly reduced. Bisindolylmaleimide reverted the effects induced by PREP1, suggesting PKCα to be a mediator of PREP1 action. Interestingly, resveratrol, a phenolic micronutrient compound, reduced the PREP1 levels, eNOSThr495, PKCα phosphorylation, and proinflammatory cytokines and increased Sod2 and Atf4 mRNA levels. The experiments performed on the aorta of 18-month-old Prep1 hypomorphic heterozygous mice (Prep1i/+) expressing low levels of this protein showed a 54 and 60% decrease in PKCα and eNOSThr495 phosphorylation and a 45% reduction in Tnf-α levels, with no change in Il-6, compared to same-age WT mice. However, a significant decrease in Sod2 and Atf4 was observed in Prep1i/+ old mice, indicating the lack of age-induced antioxidant response. These results suggest that Prep1 deficiency partially improved the endothelial function in aged mice and suggested PREP1 as a novel target of resveratrol.

Epicardial Adipose Tissue-Derived IL-1ß Triggers Postoperative Atrial Fibrillation.

Background and aims: Post-operative atrial fibrillation (POAF), defined as new-onset AF in the immediate period after surgery, is associated with poor adverse cardiovascular events and a higher risk of permanent AF. Mechanisms leading to POAF are not completely understood and epicardial adipose tissue (EAT) inflammation could be a potent trigger. Here, we aim at exploring the link between EAT-secreted interleukin (IL)-1ß, atrial remodeling, and POAF in a population of coronary artery disease (CAD) patients. Methods: We collected EAT and atrial biopsies from 40 CAD patients undergoing cardiac surgery. Serum samples and EAT-conditioned media were screened for IL-1ß and IL-1ra. Atrial fibrosis was evaluated at histology. The potential role of NLRP3 inflammasome activation in promoting fibrosis was explored in vitro by exposing human atrial fibroblasts to IL-1ß and IL-18. Results: 40% of patients developed POAF. Patients with and without POAF were homogeneous for clinical and echocardiographic parameters, including left atrial volume and EAT thickness. POAF was not associated with atrial fibrosis at histology. No significant difference was observed in serum IL-1ß and IL-1ra levels between POAF and no-POAF patients. EAT-mediated IL-1ß secretion and expression were significantly higher in the POAF group compared to the no-POAF group. The in vitro study showed that both IL-1ß and IL-18 increase fibroblasts' proliferation and collagen production. Moreover, the stimulated cells perpetuated inflammation and fibrosis by producing IL-1ß and transforming growth factor (TGF)-ß. Conclusion: EAT could exert a relevant role both in POAF occurrence and in atrial fibrotic remodeling.

The clinical impact of the Covid-19 pandemic first wave on patients with cystic fibrosis in New York.

BACKGROUND: People with cystic fibrosis (pwCF) may be at risk of complications from COVID-19 but the impact of COVID-19 on pwCF remains unknown. METHODS: We conducted a multicenter retrospective cohort study to assess the impact of the COVID-19 pandemic first wave on pwCF in the New York metropolitan area (NY) from March 1, 2020 to August 31, 2020. Objectives were to determine (1) the prevalence of COVID-19 by PCR and IgG antibody testing, (2) the clinical characteristics of COVID-19, (3) delay in routine outpatient care, and (4) the effect on anxiety and depression in pwCF. RESULTS: There were 26 COVID-19 cases diagnosed by PCR or antibody testing among the study cohort of 810 pwCF. The prevalence of COVID-19 by PCR (1.6%) and IgG antibody (12.2%) testing was low. 58% of cases were asymptomatic and 82% were managed at home. 8% were hospitalized and 1 person died. 89% of pwCF experienced delay in care. The prevalence of anxiety increased from 43% baseline to 58% during the pandemic (P<0.01). In post-hoc analysis, the proportion of patients with diabetes (38% versus 16%, P<0.01) and pancreatic insufficiency (96% versus 66%, P<0.01) were higher while CFTR modulator use was lower (46% versus 65%, P = 0.05) in pwCF who tested positive for COVID-19. CONCLUSIONS: The prevalence of COVID-19 among pwCF in NY during the pandemic first wave was low and most cases were managed at home. CFTR modulators may be protective. PwCF experienced delay in routine care and increased anxiety.