Premium
NCX1.1 and NSCCs participate in PDGF‐BB mediated cardiac myofibroblast migration and contraction
Author(s) -
Raizman Josh,
Komljenovic Jelena,
Elimban Vinit V,
Freed Darren H,
Rattan Sunil G,
Dixon Ian M.C.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb20-c
Subject(s) - myofibroblast , motility , contraction (grammar) , chemistry , contractility , microbiology and biotechnology , platelet derived growth factor receptor , medicine , biology , fibrosis , growth factor , biochemistry , receptor
Platelet‐derived growth factor (PDGF) is elevated in plasma of post‐myocardial infarct (MI) patients after MI. Participation of hypersynthetic and contractile cardiac myofibroblasts in post‐MI heart is critical for infarct scar formation and to remodeling of the damaged ventricle. The role of intracellular calcium handling in cardiac myofibroblasts as a modulator of cellular motility and contraction is unexplored, and we report on our investigation of NCX and NSCC as putative regulators of myofibroblast motility and contractility. Primary cultures of myofibroblasts and pharmacological NCX or NSCC (7.5 uM KB‐R7943 and 10 uM gadolinium (Gd 3+ ), respectively) inhibitors were applied to Transwell plates (Costar) in the presence of PDGF‐BB (50 ng/ml ‐ 24 h treatment). Collagen gel deformation assays were used to estimate cell contraction by seeding cells on pre‐formed collagen type II gels; gel contraction was analyzed at 24 h using IDL software based analysis. Immunoflouresence was used to determine expression of α‐SMA, SMemb, and NCX1.1 in cultured cells. Both motility and contraction of PDGF‐BB stimulated cells are sensitive to KB‐R7943 treatment in cells expressing NCX1.1 while Gd 3+ treatment was associated only with decreased motility of cells. Thus pharmacological inhibition of NCX1.1 concomitantly inhibits myofibroblast motility and contraction responses. We conclude that plasmalemmal Ca handling is important in PDGF‐BB mediated cardiac myofibroblast motility and function, and that the activation of specific proteins is an important determinant of downstream responses. Supported by the CIHR.