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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aorta / cytology
  • Aorta / physiology
  • Calcium Signaling / physiology*
  • Cells, Cultured
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis / physiopathology*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Disease Models, Animal
  • Endoplasmic Reticulum / metabolism
  • Genotype
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / physiology*
  • Myography
  • Swine
  • Vasoconstriction / physiology


  • Inositol 1,4,5-Trisphosphate Receptors
  • Cystic Fibrosis Transmembrane Conductance Regulator