Altered fibroblast function following myocardial infarction.
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.
Squires
Christina E
CE
Division of Cardiothoracic Surgery Research, Room 629, Strom Thurmond Research Building, Medical University of South Carolina, 114 Doughty Street, Charleston, SC 29425, USA.
Escobar
G Patricia
GP
Payne
John F
JF
Leonardi
Robert A
RA
Goshorn
Danielle K
DK
Sheats
Nina J
NJ
Mains
I Matthew
IM
Mingoia
Joseph T
JT
Flack
English C
EC
Lindsey
Merry L
ML
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
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