Osteogenic protein-1 reduces intercellular adhesion molecule-1 messenger RNA expression, infarct size and TUNEL-positive cardiomyocytes in ischemia/reperfusion rat hearts

Junichi Hayashi, Shozo Kusachi, Takashi Murakami, Tohru Miyoshi, Keigo Nakamura, Kazuya Koten, Hiroko Ogawa, Satoshi Hirohata, Yoshifumi Ninomiya, Yasushi Shiratori

Research output: Contribution to journalArticle

Abstract

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 μg/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-old 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.

Original languageEnglish
Pages (from-to)195-200
Number of pages6
JournalExperimental and Clinical Cardiology
Volume8
Issue number4
Publication statusPublished - Dec 1 2003

Keywords

  • Apoptosis
  • Inflammation
  • Ischemic heart disease
  • Matrix protein
  • Molecular biology

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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