ABSTRACT
Rationale: Angiotensin-converting enzyme 2 (ACE2) is a vasoactive enzyme involved in regulation of vascular tone and blood pressure by reducing angiotensin II and increasing ang(1-7). It is also implicated in the pathogenesis of coronaviruses including SARS-CoV-2. Epidemiological reports differ in implicating cigarette smoking as a risk factor for SARS-CoV-2 infection (COVID-19). Previous studies have been conflicting regarding the implications of cigarette smoke exposure on ACE2 signaling. We hypothesized that cigarette smoke exposure will increase ACE2 expression and impair endothelial cell function. Methods: Female 8-week-old A/J mice were randomly assigned to either air exposure or 48 minutes per day, 5 days per week of cigarette smoke exposure. Mainstream whole-body cigarette smoke exposure was delivered by the SCIREQ “InExpose” smoking system with standard 3R4F research cigarettes. Mouse were sacrificed at 1 and 12 weeks of smoke exposure, and lungs were homogenized and subjected to ACE2 ELISA (Abcam). To investigate the effect of smoking on ACE2 expression and endothelial barrier function, serum starved human pulmonary microvascular endothelial cells (PMVECs) were exposed to cigarette smoke extract (CSE). CSE was prepared at a concentration of 1 cigarette/5 ml in serumfree DMEM and quiescent PMVECs were treated with 1% CSE, 3% CSE or vehicle. Cells were processed for real-time RT-PCR and ELISA 4 hours later, assessment of apoptosis, or underwent TEER to assess endothelial cell barrier function. Results: Lung tissue ACE2 levels were significantly elevated following 1-week of cigarette smoke-exposure. This increase was accompanied by increased macrophage count in bronchoalveolar lavage. Interestingly, at 12-weeks of cigarette smoke-exposure, lung ACE2 was reduced by 15% response. Chronic cigarette smoke-exposure was accompanied by increased right ventricular systolic pressure and Fulton index. In PMVEC models, CSE dose-dependently increased ACE2 mRNA and protein expression. This was accompanied by altered EC barrier function and EC apoptosis. Conclusions: The dose and duration of cigarette smoke exposure affects ACE2 signaling, leading to altered apoptosis and endothelial cell barrier function. These findings have implications for SARS-CoV-2 pathogenesis as well as for furthering our understanding of the effects of smoking on vascular health.
ABSTRACT
Introduction: There has been a necessity for healthcare services to greatly adapt delivery of care since the onset of the COVID-19 pandemic. Virtual diabetes consultations within our paediatric department were quickly set up to ensure continued care for children and adolescents with diabetes. Objectives: The study aimed to identify if the COVID-19 lockdown in 2020 and thus, the introduction of virtual diabetic reviews, had impacted upon patient outcomes of HbA1c levels, annual diabetic blood tests and number of admissions due to diabetes. Methods: A cross-sectional study was conducted with children under the age of sixteen diagnosed with type 1 diabetes prior to 1st January 2020. All were under the care of the paediatric diabetes team at Blackpool Victoria Hospital, U.K. Data was collected on whether each patient had been reviewed virtually, whether they had undergone annual diabetic blood and urine tests, as well as the number of HbA1c tests each patient had in 2019 and 2020 and their respective levels. Pre-lockdown admissions in 2019 were compared to admissions in 2020. Results: 108 patients were included in this study;all were reviewed virtually at least once in 2020. 82.24% and 60.75% had annual review of diabetic investigations in 2019 and 2020 respectively. 92.52% had at least one HbA1c test in 2019, with the same percentage tested in 2020. There was no significant difference in the median HbA1c levels in 2019 and 2020 as shown by Wilcoxon signed-rank test for the paired samples (p = 0.9932). This was the same for patients on insulin pumps (p=0.2174). There was no significant difference in the average number of admissions for those on insulin pumps (p=0.8211), however there was a greater number of pre-lockdown admissions in 2019 for those on basal-bolus regimes than in 2020 (p=0.0056). Conclusions: Virtual diabetes care did not appear to have a detrimental effect on diabetic outcomes. This paves the way for it to continue to play an active role in delivery of paediatric diabetes care.