title: Attenuation of ischemic myocardial injury and dysfunction by cardiac fibroblast-derived factor(s).
abstract: Fibroblasts, the majority of non-cardiomyocytes in the heart, are known to release several kinds of substances such as cytokines and hormones that affect cell and tissue functions. We hypothesized that undefined substance (s) derived from cardiac fibroblasts may have the potential to protect against ischemic myocardium. To assess our hypothesis, using rats, we investigated: (1) the effect of cardiac fibroblast-conditioned medium (CM) on the viability of hypoxic cardiomyocytes in vitro, (2) the effect of CM on left ventricular (LV) function in global ischemia-reperfusion in an ex vive model, (3) the mechanism underlying cardioprotection by CM. Seventy-two hours after starting a hypoxic culture, the viability of cardiomyocytes was higher (P < 0.05) in the CM treated group (41.4%) compared to the control (20.5%). In Langendorff's preparation, 30 min after ischemia-reperfusion, LV end-diastolic pressure was lower, and LV developed pressure and -LVdP/dt were higher (P < 0.01 or P < 0.05) in the CM group than in the control, although coronary flow did not differ between the two groups. Pretreatment with a protein kinase C inhibitor or a mitochondrial ATP-sensitive K+ channel blocker attenuated these changes of LV function in the CM group. Such cardioprotection was achieved by a fraction of the CM having a molecular weight (MW) > 50,000, but not by that of the CM with a lower MW. In addition, a specific antibody against hepatocyte growth factor (HGF, MW is 84,000) did not reduce the cardioprotection afforded by CM. There may be an unknown cardioprotective substance other than HGF in rats, which mimics ischemic preconditioning and has MW > 50,000.
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan. nakazato@fmu.ac.jp
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakazato
authors.forename: Wakako
authors.initials: W
authors.lastname: Naganuma
authors.forename: Kazuei
authors.initials: K
authors.lastname: Ogawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yaoita
authors.forename: Shinya
authors.initials: S
authors.lastname: Mizuno
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yukio
authors.initials: Y
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000302:isolation & purification / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005347:Fibroblasts / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008970:Molecular Weight; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left
chemical_list: D002316:Cardiotonic Agents; D017077:Culture Media, Conditioned