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J Cyst Fibros. 2014 May;13(3):251-9. doi: 10.1016/j.jcf.2013.10.009. Epub 2013 Oct 31.

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

Author information

1
Department of Pediatrics, University of Iowa, Iowa City, IA 52242, United States.
2
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, United States.
3
Department of Pediatrics, University of Iowa, Iowa City, IA 52242, United States. Electronic address: robert-roghair@uiowa.edu.

Abstract

BACKGROUND:

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.

METHODS:

Aortic reactivity was assessed by myography, and ratiometric calcium imaging was performed in isolated vascular smooth muscle cells.

RESULTS:

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.

CONCLUSIONS:

Expression of CFTR-F508del interferes with smooth muscle cell calcium handling and decreases aortic responsiveness.

KEYWORDS:

Cystic fibrosis transmembrane conductance regulator; Endoplasmic reticulum; Inositol triphosphate receptor; Vascular smooth muscle cell

PMID:
24183914
PMCID:
PMC3972271
DOI:
10.1016/j.jcf.2013.10.009
[Indexed for MEDLINE]
Free PMC Article

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