Exacerbation of myocardial injury in transgenic mice overexpressing FGF-2 is T cell dependent.
Fibroblast growth factor-2 (FGF-2) is cardioprotective when added exogenously, stimulates cardiac myocyte proliferation, and is a mediator of tissue repair after injury. Furthermore, transgenic (TG) mice overexpressing FGF-2 in cardiac muscle demonstrate increased resistance to injury in an isolated heart model of ischemia-reperfusion. We investigated how increasing the endogenous FGF-2 levels in the heart affects the extent of myocardial damage induced by isoproterenol in vivo. Histopathological evaluation of hearts after intraperitoneal injection of isoproterenol yielded significantly higher scores for myocardial damage in FGF-2 TG lines compared with non-TG mice. After 1 day, FGF-2 TG mouse hearts displayed more cellular infiltration correlating with increased tissue damage. Immunostaining of non-TG and FGF-2 TG mouse hearts showed the presence of leukocytes in the infiltrate, including T cells expressing FGF receptor-1. Treatment of mice with T cell suppressors cyclosporin A and anti-CD3epsilon significantly decreased the level of myocardial injury observed after isoproterenol and equalized the histopathology scores in FGF-2 TG and non-TG hearts. These data demonstrate a direct T cell involvement in the response to isoproterenol-induced injury in vivo. Moreover, the findings indicate that the exacerbation of myocardial damage in FGF-2 TG mice was dependent on T cell infiltration, implicating FGF-2 in the inflammatory response seen in cardiac tissue after injury in vivo.
Meij
Johanna T A
JT
Department of Physiology, University of Manitoba, Winnipeg R3E 3J7, Manitoba, Canada R2H 2A6.
Sheikh
Farah
F
Jimenez
Sarah K
SK
Nickerson
Peter W
PW
Kardami
Elissavet
E
Cattini
Peter A
PA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D006331:Heart Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007545:Isoproterenol; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009206:Myocardium / Q000276:immunology* / Q000473:pathology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013566:Sympathomimetics; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; C115335:CD3E protein, human; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell; D013566:Sympathomimetics; D016222:Fibroblast Growth Factor 2; D016572:Cyclosporine; D007545:Isoproterenol