Search

Your search keyword '"Stolarz, Amanda J."' showing total 20 results
Start Over Author "Stolarz, Amanda J."
20 results on '"Stolarz, Amanda J."'

1. Rhythmic Contractions of Lymph Vessels and Lymph Flow Are Disrupted in Hypertensive Rats.

Author

Pal, Soumiya, Bagchi, Ashim K., Henry, David S., Landes, Reid D., Mu, Shengyu, Rhee, Sung W., Rusch, Nancy J., and Stolarz, Amanda J.

Abstract

BACKGROUND: Hypertension increases the risk of lymphedema in patients with comorbidities, but whether hypertension directly compromises lymph vessel (LV) function and lymph flow is unclear. We compared the contractions of mesenteric LVs ex vivo and lymph flow in vivo between normotensive and Ang II (angiotensin II)-induced hypertensive rats and explored the ionic basis of contractile patterns. Key studies were recapitulated in spontaneously hypertensive rats and control Wistar-Kyoto rats. METHODS: Video microscopy continuously recorded the diameters of cannulated rat mesenteric LVs, and high-speed optical imaging estimated mesenteric lymph flow in vivo. Jess capillary Western electrophoresis evaluated expression levels of ion channel proteins. RESULTS: Isolated LVs from Ang II-induced hypertensive rats exhibited dysrhythmic contractions, whereas LVs from both Ang II-induced hypertensive rats and spontaneously hypertensive rats exhibited reduced diastolic diameters and cross-sectional flow. Mesenteric lymph flow in vivo was 2.9-fold lower in Ang II-induced hypertensive rats compared with normotensive rats. Surprisingly, the LVs from Ang II-induced hypertensive rats expressed fewer intact L-type Ca2+ channel pore proteins and more modulatory cleaved C-terminal fragments. However, pharmacological block of voltage-gated K+ channels but not other K+ channel types in control LVs established the pattern of contractile dysfunction observed in hypertension. Jess capillary Western electrophoresis analysis confirmed a loss of Shaker-type KV1.2 channels in LVs from hypertensive rats. CONCLUSIONS: We provide initial evidence of lymphatic contractile dysfunction and compromised lymph flow in hypertensive rats, which may be caused by a loss of KV1.2 channels in the lymphatic muscle cells. [ABSTRACT FROM AUTHOR]

Published
2025
Full Text
View/download PDF

18. Fenofibrate Attenuates Neutrophilic Inflammation in Airway Epithelia: Potential Drug Repurposing for Cystic Fibrosis

Author

Stolarz, Amanda J., Farris, Ryan A., Wiley, Charla A., O'Brien, Catherine E., and Price, Elvin T.

Subjects
Inflammation, Chemokine CXCL5, Cystic Fibrosis, Dose-Response Relationship, Drug, Neutrophils, Tumor Necrosis Factor-alpha, Gene Expression Profiling, Interleukin-8, Drug Repositioning, Granulocyte-Macrophage Colony-Stimulating Factor, Bronchi, Epithelial Cells, Fenofibrate, Original Research Articles, Forced Expiratory Volume, Granulocyte Colony-Stimulating Factor, Humans, Chemokines, Cells, Cultured
Abstract

A hallmark of cystic fibrosis (CF) lung disease is neutrophilic airway inflammation. Elevated neutrophil counts have been associated with decreased forced expiratory volume in 1 second and poor clinical measures in patients with CF. Interleukin 8 (IL-8), epithelial neutrophil activating protein 78 (ENA-78), tumor necrosis factor alpha (TNF-α), granulocyte macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) contribute to neutrophil activation and disease pathogenesis in the airways of patients with CF. Drugs that modify the production of these chemokines in the airways could potentially benefit CF patients. Thus, we determined the effects of fenofibrate on their production in cell populations obtained from the airways. Human small airway epithelial cells and CF bronchial epithelial cells were treated with IL-1β to induce inflammation. We cotreated the cells with fenofibrate at concentrations ranging from 10 to 50 μM to determine if this drug could attenuate the inflammation. IL-8, ENA-78, TNF-α, GM-CSF, and G-CSF production were measured from the cell culture supernates by ELISA. ANOVA statistical testing was conducted using SPSS 17.0. IL-1β increased the production of each of the chemokines by several fold. Fenofibrate reduced IL-1β induced production of each of these neutrophilic chemokines at the concentrations used. IL-1β increases the production of neutrophilic chemokines in airway epithelial cells. Cotreatment with fenofibrate blunts these processes. Fenofibrate should be explored as a therapeutic option to modulate the abundant neutrophilic inflammation observed in CF.

Published
2015

Catalog

Books, media, physical & digital resources
See catalog results