BACKGROUND: Osteogenic protein, a member of the transforming growth factor-beta superfamily, has been reported to decrease the expression of intercellular adhesive molecules and prevent neutrophil accumulation and activity in tissue injury. OBJECTIVE: To examine the effects of osteogenic protein on ischemia/reperfusion in rat hearts. METHODS: Reperfusion was established after a 90 min ligation of the proximal left coronary artery in rats. Recombinant human osteogenic protein-1 (200 mug/kg) was administered via the femoral vein just before reperfusion. Intercellular adhesion molecule-1 (ICAM-1) messenger RNA (mRNA) expression and infarct size were evaluated using Northern blotting and triphenyl tetrazolium chloride staining, respectively. Terminal deoxynucleotidyl transferase mediated biotin-16-2'-deoxyuridine-5'-triphosphate nick end labeling (TUNEL) staining was also performed. RESULTS: In osteogenic protein-1 treated rats, the expression of ICAM-1 mRNA in ischemia/reperfusion hearts rapidly increased 4 h after reperfusion, although, the increase was lower than that observed in the vehicle-treated hearts (7.4+/-1.6-fold versus 14.6+/-3.7-fold increase compared to the increase observed in preligation control hearts, respectively). Similarly, in day 1 and day 7 hearts, the increase in ICAM-1 mRNA expression was significantly lower in ischemia/reperfusion hearts from rats treated with osteogenic protein-1 than in vehicle-treated rats (2.5+/-0.1-fold versus 5.8+/-2.3-fold and 1.5+/-0.3-fold versus 3.5+/-0.2-fold, respectively). Infarct size in rats treated with osteogenic protein-1 was significantly smaller than that observed in rats treated with vehicle (13.1+/-1.2% versus 28.5+/-5.7% of the left ventricle, P<0.01). The percentage of TUNEL-positive cardiomyocytes in ischemia/reperfusion hearts in rats treated with osteogenic protein-1 was significantly lower than in rats treated with vehicle (17.1+/-5.3% versus 31.1+/-4.5%, P<0.01). CONCLUSION: The present study demonstrated that recombinant human osteogenic protein-1 suppressed ICAM-1 mRNA expression, reduced infarct size and decreased TUNEL-positive cardiomyocytes in ischemic/reperfused rat hearts.
BACKGROUND: Osteogenic protein, a member of the transforming growth factor-beta superfamily, has been reported to decrease the expression of intercellular adhesive molecules and prevent neutrophil accumulation and activity in tissue injury. OBJECTIVE: To examine the effects of osteogenic protein on ischemia/reperfusion in rat hearts. METHODS: Reperfusion was established after a 90 min ligation of the proximal left coronary artery in rats. Recombinant humanosteogenic protein-1 (200 mug/kg) was administered via the femoral vein just before reperfusion. Intercellular adhesion molecule-1 (ICAM-1) messenger RNA (mRNA) expression and infarct size were evaluated using Northern blotting and triphenyl tetrazolium chloride staining, respectively. Terminal deoxynucleotidyl transferase mediated biotin-16-2'-deoxyuridine-5'-triphosphate nick end labeling (TUNEL) staining was also performed. RESULTS: In osteogenic protein-1 treated rats, the expression of ICAM-1 mRNA in ischemia/reperfusion hearts rapidly increased 4 h after reperfusion, although, the increase was lower than that observed in the vehicle-treated hearts (7.4+/-1.6-fold versus 14.6+/-3.7-fold increase compared to the increase observed in preligation control hearts, respectively). Similarly, in day 1 and day 7 hearts, the increase in ICAM-1 mRNA expression was significantly lower in ischemia/reperfusion hearts from rats treated with osteogenic protein-1 than in vehicle-treated rats (2.5+/-0.1-fold versus 5.8+/-2.3-fold and 1.5+/-0.3-fold versus 3.5+/-0.2-fold, respectively). Infarct size in rats treated with osteogenic protein-1 was significantly smaller than that observed in rats treated with vehicle (13.1+/-1.2% versus 28.5+/-5.7% of the left ventricle, P<0.01). The percentage of TUNEL-positive cardiomyocytes in ischemia/reperfusion hearts in rats treated with osteogenic protein-1 was significantly lower than in rats treated with vehicle (17.1+/-5.3% versus 31.1+/-4.5%, P<0.01). CONCLUSION: The present study demonstrated that recombinant humanosteogenic protein-1 suppressed ICAM-1 mRNA expression, reduced infarct size and decreased TUNEL-positive cardiomyocytes in ischemic/reperfused rat hearts.
Authors: F Squadrito; D Altavilla; G Squadrito; A Saitta; B Deodato; M Arlotta; L Minutoli; C Quartarone; M Ferlito; A P Caputi Journal: J Mol Cell Cardiol Date: 2000-03 Impact factor: 5.000
Authors: S Vukicevic; V Basic; D Rogic; N Basic; M S Shih; A Shepard; D Jin; B Dattatreyamurty; W Jones; H Dorai; S Ryan; D Griffiths; J Maliakal; M Jelic; M Pastorcic; A Stavljenic; T K Sampath Journal: J Clin Invest Date: 1998-07-01 Impact factor: 14.808