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


CONCLUSIONS
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.
Hayashi
Junichi
J
Department of Medicine and Medical Science, Okayama University Graduates School of Medicine and Dentistry;
Kusachi
Shozo
S
Murakami
Takashi
T
Miyoshi
Tohru
T
Nakamura
Keigo
K
Koten
Kazuya
K
Ogawa
Hiroko
H
Hirohata
Satoshi
S
Ninomiya
Yoshifumi
Y
Shiratori
Yasushi
Y