Publications by authors named "B Wojciak-Stothard"
Background And Purpose: Vasoreactivity of pulmonary arteries regulates blood flow through the lungs. Excessive constriction of these vessels contributes to pulmonary arterial hypertension (PAH), a progressive and incurable condition, resulting in right heart failure. The search for new and improved drug treatments is hampered by laboratory models that do not reproduce the vasoactive behaviour of healthy and diseased human arteries.
View Article and Find Full Text PDFARF6 as a Novel Activator of HIF-2α in Pulmonary Arterial Hypertension.
Am J Respir Cell Mol Biol
November 2024
Article Synopsis
- ARF6, a GTPase linked to cancer metastasis, is activated in lung endothelial cells during pulmonary arterial hypertension (PAH) and influences several key biological pathways.
- Proteomic analysis of human pulmonary artery endothelial cells revealed that active ARF6 is associated with increased expression of hypoxia-inducible factor (HIF-2), essential for PAH, while showing lesser impact on HIF-1.
- A novel ARF6 inhibitor, chlortetracycline (CTC), demonstrated potential in reducing HIF-2 activation and mitigating symptoms of PAH, indicating a new therapeutic approach that may target this pathway for better management of the disease.
Background: βAR (beta-1 adrenergic receptor) and βAR (beta-2 adrenergic receptor)-mediated cyclic adenosine monophosphate signaling has distinct effects on cardiac function and heart failure progression. However, the mechanism regulating spatial localization and functional compartmentation of cardiac β-ARs remains elusive. Emerging evidence suggests that microtubule-dependent trafficking of mRNP (messenger ribonucleoprotein) and localized protein translation modulates protein compartmentation in cardiomyocytes.
View Article and Find Full Text PDFPulmonary arterial hypertension (PAH) is an unmet clinical need. The lack of models of human disease is a key obstacle to drug development. We present a biomimetic model of pulmonary arterial endothelial-smooth muscle cell interactions in PAH, combining natural and induced bone morphogenetic protein receptor 2 (BMPR2) dysfunction with hypoxia to induce smooth muscle activation and proliferation, which is responsive to drug treatment.
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