title: Altered fibroblast function following myocardial infarction.
abstract: Adequate wound healing and scar formation is an essential response to myocardial infarction (MI), and fibroblasts are primary cellular components regulating the process. How fibroblast functions are altered post-MI and to what extent these abnormalities persist in vitro is not well understood. Accordingly, we isolated myocardial fibroblasts from MI and non-MI (remote) regions at 7 days post-MI (n=35) and from the free wall and septum of unoperated control C57BL/6 mice (n=14). Proliferation was increased 182+/-28% in MI, but not in remote, fibroblasts compared with unoperated controls (P=0.01). Migration decreased 61+/-8%, adhesion to laminin decreased 79+/-8%, adhesion to collagen IV increased 196+/-27%, and collagen synthesis increased 169+/-24% in fibroblasts isolated from the MI region (all P<0.05). Migration, adhesion, and collagen synthesis changes were similar in remote fibroblasts, and the phenotypic differences were maintained through passage four. Transforming growth factor beta1 (TGFbeta1) is a bioactive molecule that has been shown to affect fibroblast function. Stimulation of unoperated control fibroblasts with 10 ng/ml TGFbeta(1) increased proliferation 137+/-7% (P=0.03 vs. unstimulated), increased adhesion to collagen IV 149+/-6% (P<0.01), and increased collagen I levels 187+/-10% (P=0.01). TGFbeta1 may, therefore, explain some of the changes in post-MI fibroblast phenotype. These data demonstrate for the first time region specific alterations in post-MI fibroblast biology that are maintained in vitro. Additionally, our model provides a novel in vitro template for examining the cellular mechanisms of wound healing and scar formation post-MI.
authors.affiliation: Division of Cardiothoracic Surgery Research, Room 629, Strom Thurmond Research Building, Medical University of South Carolina, 114 Doughty Street, Charleston, SC 29425, USA.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Squires
authors.forename: G Patricia
authors.initials: GP
authors.lastname: Escobar
authors.forename: John F
authors.initials: JF
authors.lastname: Payne
authors.forename: Robert A
authors.initials: RA
authors.lastname: Leonardi
authors.forename: Danielle K
authors.initials: DK
authors.lastname: Goshorn
authors.forename: Nina J
authors.initials: NJ
authors.lastname: Sheats
authors.forename: I Matthew
authors.initials: IM
authors.lastname: Mains
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Mingoia
authors.forename: English C
authors.initials: EC
authors.lastname: Flack
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000096:biosynthesis; D000070818:Discoidin Domain Receptors; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D011975:Receptors, Mitogen / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
chemical_list: D001323:Autoantibodies; D019332:Endothelin-1; D011975:Receptors, Mitogen; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C051931:myasthenia gravis anti-skeletal muscle antibody; D000804:Angiotensin II; D003094:Collagen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases