Genotype-specific alterations in vascular smooth muscle cell function in cystic fibrosis piglets

Jinny J Guo; David A Stoltz; Vivian Zhu; Kenneth A Volk; Jeffrey L Segar; Paul B McCray; Robert D Roghair

doi:10.1016/j.jcf.2013.10.009

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Genotype-specific alterations in vascular smooth muscle cell function in cystic fibrosis piglets

Journal article

Open access

Peer reviewed

Genotype-specific alterations in vascular smooth muscle cell function in cystic fibrosis piglets

Jinny J Guo, David A Stoltz, Vivian Zhu, Kenneth A Volk, Jeffrey L Segar, Paul B McCray and Robert D Roghair

Journal of cystic fibrosis, Vol.13(3), pp.251-259

05/2014

DOI: 10.1016/j.jcf.2013.10.009

PMCID: PMC3972271

PMID: 24183914

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https://doi.org/10.1016/j.jcf.2013.10.009View

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Abstract

The most common CF-causing mutations interfere with CFTR trafficking from the endoplasmic reticulum (CFTR-F508del) or prematurely terminate transcription (CFTR-null). We suspected that genotype-specific patterns of CFTR expression would have differential effects on smooth muscle cell calcium signaling and hence vascular tone. We hypothesized that compared to wild-type or CFTR-null aorta, aorta from CFTR-F508del (dF) piglets will have reduced endoplasmic reticulum calcium mobilization and decreased vasoconstriction. Aortic reactivity was assessed by myography, and ratiometric calcium imaging was performed in isolated vascular smooth muscle cells. Aorta from dF piglets had reduced myogenic tone (P<0.001) and decreased constriction to KCl (P<0.05). Combined inhibition of ryanodine and IP3 receptors decreased wild-type and CFTR-null responses to levels seen in dF aorta. Compared to wild-type cells, dF-expressing smooth muscle cells had reduced calcium transients, while CFTR-null cells had decreased baseline intracellular calcium concentrations. Expression of CFTR-F508del interferes with smooth muscle cell calcium handling and decreases aortic responsiveness.

Vascular smooth muscle cell

Cystic fibrosis transmembrane conductance regulator

Inositol triphosphate receptor

Endoplasmic reticulum

Details

Title: Subtitle: Genotype-specific alterations in vascular smooth muscle cell function in cystic fibrosis piglets
Creators: Jinny J Guo - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, United States
David A Stoltz - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, United States
Vivian Zhu - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, United States
Kenneth A Volk - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, United States
Jeffrey L Segar - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, United States
Paul B McCray - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, United States
Robert D Roghair - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, United States
Resource Type: Journal article
Publication Details: Journal of cystic fibrosis, Vol.13(3), pp.251-259
Publisher: Elsevier B.V
DOI: 10.1016/j.jcf.2013.10.009
PMID: 24183914
PMCID: PMC3972271
ISSN: 1569-1993
eISSN: 1873-5010
Language: English
Date published: 05/2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Neonatology; Internal Medicine
Record Identifier: 9984025459702771

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