Purpose of Study Prenatal exposure to bacterial products increases the risk of bronchopulmonary dysplasia (BPD) in extremely preterm infants. Abnormal lung vasculogenesis may be a component of BPD pathogenesis. To test if bacterial products might alter vascular development, we studied the effects of E. coli lipopolysaccharide (LPS) on experimental mouse models of vasculogenesis. Methods Fetal lung explants were obtained from E16 (term E20) Tie-2-GFP and SCL-YFP mice. Both of these transgenic reporter strains express fluorescent proteins in fetal lung endothelial cells. GFP- and YFP-expressing cells were visualized by confocal microscopy. In vitro vasculogenesis was assayed by culturing immortalized pulmonary microvascular endothelial cells cultured on Matrigel. We measured endothelial cell migration using both a modified Transwell filter system and an artificial wound healing assay. We obtained quantitative image analysis data using Histometrix software. Results To test the effect of bacterial products on pulmonary vasculogenesis, we cultured saccular stage fetal lung explants from Tie-2 GFP mice for 72 hours in the presence of LPS. In control explants, GFP-expressing endothelial cells were detected around developing saccular airways. Adding LPS to the culture media increased the number of endothelial cells around the airways by 70% (n = 6, p = .001). We observed similar results using explants from SCL-YFP mice. These observations suggested that LPS might stimulate vasculogenesis in the fetal lung mesenchyme. To test if LPS could directly act on cultured pulmonary microvascular endothelial cells, we measured vasculogenesis in vitro. When cultured on Matrigel, pulmonary microvascular endothelial cells formed elongated capillary-like tube structures. Addition of LPS to the Matrigel and media increased tube length by 45% compared with controls (n = 6, p Conclusions LPS increased vasculogenesis in our fetal mouse lung explant model and in our in vitro endothelial cell assays. We have yet to determine if LPS subsequently alters capillary remodeling or vascular maturation during alveolar development. These experiments may clarify the mechanisms of abnormal vascular development in BPD.

Vasculogenesis

Matrigel

Source

Cite

Citations (0)

Genomic Biomarkers of Poor Outcome in Patients with T-Cell Lymphoblastic Lymphoma

Blood (2024)

Haley Newman Lahari Uppuluri Rawan Shraim Carl E. Allen Kara L. Davis

Lymphoblastic lymphoma

10.1182/blood-2024-203827

Cite

Citations (0)

Investigation of age-related in-hospital outcomes of left atrial appendage occlusion in germany

European Heart Journal (2024)

Jakob Voran Hatim Seoudy Mohamed Lèye Felix Kreidel David B. Frank

Abstract Background The aim of this study was to assess demographics, in-hospital mortality and baseline characteristics of hospital cases with a left atrial appendage occlusion (LAAO) procedure in relation to patient age. Methods This is a retrospective observational analysis of all German in-hospital cases from 2016 to 2022 with a coded LAAO procedure using the Diagnose Related Groups (DRG) statistics database of the Research Data Center of the Federal Statistical Office. Results In total 40435 cases were observed in the investigated time period. Over the 5 years studied we found a significant shift towards an older patient collective. Compared to 28,3% in 2016, in 2022 40,1% of all patients were over 80 years of age (a rise of 152 %). Cases of patients with over 85 years of age increased from 7.7 % to 11.4 % during the same time period. We observed an in-hospital death rate for patients <70, 70-75, 80-85 and >85 years of age in 0.8, 1.0, 1.4 and 2.2 % respectively. Further we saw significant higher rates of intensified care treatment, pericardial effusion, acute kidney injury and red blood cell transfusion for patients >80 years of age. In unadjusted and adjusted logistic regression models age was significantly associated with a higher rate of in-hospital death. Conclusions In this study we present real world data from a health-care-system level. Our main findings were an increasing age in patients undergoing LAAO procedures and an independent association of age with in-house mortality and complications. This data provides a further basis to balance risks and benefits of LAAO procedure as a preventive treatment.

Appendage

Atrial Appendage

10.1093/eurheartj/ehae666.2313

Cite

Citations (0)

Bronchopulmonary Dysplasia with Pulmonary Hypertension Associates with Loss of Semaphorin Signaling and Functional Decrease in FOXF1 Expression

bioRxiv (Cold Spring Harbor Laboratory) (2024)

Shawyon P. Shirazi Nicholas M. Negretti Christopher S. Jetter Alexandria L. Sharkey Shriya Garg

Lung injury in preterm infants leads to structural and functional respiratory deficits, with a risk for bronchopulmonary dysplasia (BPD) that in its most severe form is accompanied by pulmonary hypertension (PH). To examine cellular and molecular dynamics driving evolving BPD in humans, we performed single-cell RNA sequencing of preterm infant lungs in early stages of BPD and BPD+PH compared to term infants. Analysis of the endothelium revealed a unique aberrant capillary cell-state primarily in BPD+PH marked by

Bronchopulmonary Dysplasia

10.1101/2024.08.27.609955

Cite

Citations (0)

A Spatiotemporal Cell Atlas of Cardiopulmonary Progenitor Cell Allocation During Development

Hongbo Wen Prashant Chandrasekaran Annabelle Jin Josh Pankin MinQi Lu

10.2139/ssrn.4728196

Cite

Citations (0)