Higher soluble thrombomodulin and angiogenic markers in continuous flow left ventricular assist device-supported patients associated with arteriovenous malformation and nonsurgical bleedingMuthiah, Dunn, Eckford
et alJHLT Open (2024) 6, 100133
Abstract: Bleeding complications are a bane of continuous flow left ventricular assist devices (cfLVAD); gastrointestinal bleeding (GIB) from arteriovenous malformation (AVM) predominating. We hypothesized that shear stress disrupts vascular endothelium altering angiogenesis and contributing to bleeding. We profiled markers of endothelial dysfunction (soluble thrombomodulin [sTM]) and angiogenesis (angiopoietin-1 [Ang-1], angiopoietin-2 [Ang-2]) in 21 patients implanted with a centrifugal cfLVAD. Bleeding episodes were documented in 11 patients, 8 had GIB, 4 of whom had AVMs. We observed a dynamic change in sTM and Ang-2/Ang-1 ratio following cfLVAD support (p = 0.030 and p = 0.025, respectively). Bleeding patients had higher sTM and Ang-2/Ang-1 ratios than patients with no bleeding (p = 0.04 and p = 0.06, respectively). At D180, patients with AVMs had significantly higher Ang-2/Ang-1 ratios vs patients without proven AVMs (p = 0.006). We conclude that bleeding in cfLVAD-supported patients is associated with alteration in endothelial/vascular homeostasis, possibly contributing to AVM formation.© 2024 International Society for Heart and Lung Transplantation.
Endothelial Dysfunction Markers Correlate with the Time Since Completion of Tuberculosis Treatment and the Number of Previous Tuberculosis EpisodesJumaar, Jacobs, Payne
et alInfect Dis Rep (2025) 17 (2)
Abstract: Background: Despite "successful" treatment, some lung tuberculosis (TB) patients develop long-term lung impairments that includes damage to the parenchyma and reduced function, which may predispose them to diseases like pulmonary hypertension. However, this is not well understood. Therefore, we investigated whether previous or current TB patients would display elevated biomarkers of endothelial dysfunction and vascular remodeling. Methods: We performed assays for ADMA, VCAM-1, VEGF, angiopoietin-1, TBARS, NT-pro-BNP, and cardiac troponin-I. We further stratified the patients based on 1, 2, 3, and >3 previous TB episodes, and 1-5 yrs, 5-10 yrs, 10-15 yrs and >15 yrs after the last TB treatment completion. We also assessed correlations between the biomarkers and the number of previous TB episodes or the time since the completion of the last TB treatment. Results: ADMA was 70 times higher, VEGF was 2000 times higher and angiopoietin-1 was 6500 times higher than the normal range. NT-pro-BNP and cardiac troponin-I were undetected, and TBARS levels were low. There was a positive linear relationship between the number of previous TB episodes and angiopoietin-1, and between VEGF and the number of previous TB episodes. ADMA, VCAM-1 and TBARS exhibited a weak and negative linear association with the number of previous TB episodes. A negligible negative linear association was observed between the time since the completion of the last TB treatment and angiopoietin-1, VEGF and ADMA. Conclusions: Therefore, having >1 previous TB episode, despite the successful completion of TB treatment, associates with an increased risk of endothelial dysfunction/angiogenesis or vascular remodeling.
Placental malaria infection is associated with downregulation of STAT-6 and ANG-1 in decidual macrophagesOwino, Kijogi, Anzala
et alFront Immunol (2025) 16, 1497936
Abstract: Macrophages play a crucial immunological role in maintaining pregnancy. Placental malaria infection may cause dysfunction in decidual macrophages which then culminates in the associated pregnancy complications. Here, we determined the influence of placental malaria on decidual macrophages, by assessing their distribution based on their unique phenotypes, and examining their expression levels of transcription factors as well as angiogenic factors, in placentas from women living in a malaria-endemic area.We compared these macrophage parameters in placentas from malaria infected women to those from the uninfected women. Placentas were collected upon delivery and malaria infection determined by histology together with PCR from dry blood spots obtained from placental blood. Following enzymatic dissociation of placental tissue, immune cells were enriched from the total population of placental cells by density centrifugation. Macrophage phenotypic characteristics were then analyzed from the placental immune cells by flow cytometry. The expression of surface markers CD68, CD80, CD86, CD163, CD206, and CD209, was used to delineate the macrophage populations. For gene expression profiling, macrophages were isolated from the placental immune cells and the expression level of transcription factors STAT-1, IRF-5, STAT-6, c-Maf and angiogenic factors ANG-1, ANG-2 and VEGF determined by qPCR.We found no difference in the total macrophage populations and M1 and M2 macrophage profiles between uninfected and infected placentas, however, M2 macrophages were significantly higher compared to their M1 counterparts regardless of infection status. Notably, the gene expression levels of the transcription factor STAT-6 and angiogenic factor ANG-1 were significantly lower in infected placentas. These findings provide a basis for further understanding of the role of placental macrophages in placental malaria pathogenesis. Analysis of the functional consequences of these observations is needed to determine if these factors can be explored to reprogram macrophage polarization to desired state.Copyright © 2025 Owino, Kijogi, Anzala, Walong, Jael, Nyanjom, Eric, Kanoi and Gitaka.