Abstract
Abstract 130: Cftr Is Essential For Endothelium-dependent Vasorelaxation
Arteriosclerosis, thrombosis, and vascular biology, Vol.44(Suppl_1)
05/2024
DOI: 10.1161/atvb.44.suppl_1.130
Abstract
Abstract only Genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene lead to cystic fibrosis (CF) which causes multiple health issues including lung disease and diabetes. Importantly, along with other health conditions, CF patients are long known to have impaired vascular function. Specifically, endothelium-dependent vasorelaxation is impaired in people with CF. However, the molecular mechanism(s) involved in the impairment of endothelial function in CF is not known. Since impaired endothelial function is an established risk factor for cardiovascular diseases, we investigated how CFTR regulates vascular endothelial function. We evaluated coronary arteries of CFTR -/- and littermate wild type piglets and noted profound endothelial dysfunction in coronary arteries of CFTR -/- piglets (n=10-12 rings/3 piglets). Next, we generated a mouse model with endothelium-specific deletion of CFTR (e-CFTR -/- ). Aortic rings of e-CFTR -/- mice showed a significant delay in endothelium-dependent vasorelaxation (P<0.001; n=20 rings /5 mice). To determine the molecular signaling mediating this effect, we used a pharmacological inhibitor of CFTR (CFTRinh-172) and examined changes in endothelial nitric oxide synthase (eNOS). CFTRinh-172 treatment (10 μM, 5 days) led to a significant reduction in total and S1177 phosphorylated level of eNOS in human coronary artery endothelial cells (P<0.01 and P<0.05; n=3). In addition, CFTRinh-172 treated endothelial cells exhibited increased inflammation and altered endothelial cell metabolism (n=6; P<0.001). Together, these findings suggest that CFTR regulates eNOS and cellular metabolism in endothelial cells and therefore, functional CFTR is essential for vascular endothelial function. This fundamental role of CFTR in endothelial function will have future translational value in treating people with CF.
Details
- Title: Subtitle
- Abstract 130: Cftr Is Essential For Endothelium-dependent Vasorelaxation
- Creators
- Shravan Kumar Uppulapu - University of IowaJITENDRA Kumar - University of IowaSujata Kumari - University of IowaCraig Hodges - Case Western Reserve UniversityDavid Stoltz - University of IowaSantosh Kumar - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.44(Suppl_1)
- DOI
- 10.1161/atvb.44.suppl_1.130
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Language
- English
- Date published
- 05/2024
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine; Pulmonary, Critical Care, and Occupational Medicine
- Record Identifier
- 9984687767102771
Metrics
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