Genotype-specific alterations in vascular smooth muscle cell function in cystic fibrosis piglets. J Cyst Fibros 2014 May;13(3):251-9
Date
11/05/2013Pubmed ID
24183914Pubmed Central ID
PMC3972271DOI
10.1016/j.jcf.2013.10.009Scopus ID
2-s2.0-84897111753 12 CitationsAbstract
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.
Author List
Guo JJ, Stoltz DA, Zhu V, Volk KA, Segar JL, McCray PB Jr, Roghair RDAuthor
Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAorta
Calcium Signaling
Cells, Cultured
Cystic Fibrosis
Cystic Fibrosis Transmembrane Conductance Regulator
Disease Models, Animal
Endoplasmic Reticulum
Genotype
Inositol 1,4,5-Trisphosphate Receptors
Muscle, Smooth, Vascular
Myography
Swine
Vasoconstriction
