title: The participation of the Na+-Ca2+ exchanger in primary cardiac myofibroblast migration, contraction, and proliferation.
abstract: Cardiac ventricular myofibroblast motility, proliferation, and contraction contribute to post-myocardial infarct wound healing, infarct scar formation, and remodeling of the ventricle remote to the site of infarction. The Na+-Ca2+ exchanger (NCX1) is involved in altered calcium handling in cardiac myocytes during cardiac remodeling associated with heart failure, however, its role in cardiac myofibroblast cell function is unexplored. In this study we investigated the involvement of NCX1 as well as the role of non-selective-cation channels (NSCC) in cardiac myofibroblast cell function in vitro. Immunofluorescence and Western blots revealed that P1 cells upregulate alpha-smooth muscle actin (alphaSMA) and embryonic smooth muscle myosin heavy chain (SMemb) expression. NCX1 mRNA and proteins as well as Ca(v)1.2a protein are also expressed in P1 myofibroblasts. Myofibroblast motility in the presence of 50 ng/ml PDGF-BB was blocked with AG1296. Myofibroblast motility, contraction, and proliferation were sensitive to KB-R7943, a specific NCX1 reverse-mode inhibitor. In contrast, only proliferation and contraction, but not motility were sensitive to nifedipine, while gadolinium (NSCC blocker) was only associated with decreased motility. ML-7 treatment was associated with inhibition of the chemotactic response and contraction. Thus cardiac myofibroblast chemotaxis, contraction, and proliferation were sensitive to different pharmacologic treatments suggesting that regulation of transplasmalemmal calcium movements may be important in growth factor receptor-mediated processes. NCX1 may represent an important moiety in suppression of myofibroblast functions.
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Raizman
authors.forename: Jelena
authors.initials: J
authors.lastname: Komljenovic
authors.forename: Rose
authors.initials: R
authors.lastname: Chang
authors.forename: Cicie
authors.initials: C
authors.lastname: Deng
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Bedosky
authors.forename: Sunil G
authors.initials: SG
authors.lastname: Rattan
authors.forename: Ryan H
authors.initials: RH
authors.lastname: Cunnington
authors.forename: Darren H
authors.initials: DH
authors.lastname: Freed
authors.forename: Ian M C
authors.initials: IM
authors.lastname: Dixon
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000378:metabolism; D001381:Azepines / Q000378:metabolism; D000077214:Becaplermin; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000378:metabolism; D005682:Gadolinium / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009281:Naphthalenes / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000199:Actins; D000889:Anti-Arrhythmia Agents; D001381:Azepines; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D019831:Sodium-Calcium Exchanger; C070571:ML 7; D000077214:Becaplermin; D005682:Gadolinium; D020797:Receptor, Platelet-Derived Growth Factor beta; D009219:Myosin-Light-Chain Kinase; D013890:Thiourea