Serum Hepatocyte Growth Factor Level as the Biomarker for Postoperative Intimal Hyperplasia

Abstract

Postoperative intimal hyperplasia is still the major cause of the vein graft occlusion. It may be useful to find the biomarker for the progression of postoperative intimal hyperplasia. The endothelial injury is considered as the first step for postoperative intimal hyperplasia. Hepatocyte growth factor (HGF) is not only the organ specific growth actor, but also the vascular endothelial growth factor. Edaravone (Radicut, Mitsubishi Tanabe Pharma Co., Japan) is not only the first free radical scavenger commercially available, but also alleviates the endothelial injury in vivo. In this study, we evaluated whether serum HGF levels can be the biomarker for postoperative intimal hyperplasia in the rat model. Moreover, we estimated whether edaravone can suppress postoperative intimal hyperplasia. In the 17 male rats (mean weight 498 ± 53 g), we interposed the right epigastric vein graft into the common femoral artery with 10-0 interrupted sutures, as previously described. The rats were divided into two groups: the Edaravone group, which received preoperative administration of edaravone (3.0 mg/kg) into peritoneal cavity; and the control group, which received the same dose of saline. Vein grafts from each group were stained with hematoxylin and eosin and Elastica Verhoeff’s van Gieson’s. Three unoperated right epigastric veins were also examined a Shame. The initial areas of vein graft were measured using computerized planimetry (NIH Image Ver. 1.61). Serum HGF levels were also measured and compared (unpaired t-test). This study was approved by the Hyogo College of Medicine Animal Research Committee (No. 235). The average of intimal area in Group Control were gradually increased (30 ± 16 × 10-3 mm2 at 2 weeks and 434 ±111 × 10-3 mm2 at 4 weeks), which were significantly suppressed in the Edaravone group (53 ± 54 × 10-3 mm2 at 4 weeks; P < .01). Serum HGF levels were also gradually increased (4.94 ± 0.50 ng/mL at 2 weeks and 7.20 ±1.40 ng/mL at 4 weeks), comparing with that of Shame (3.96 ± 0.22 ng/mL; P < .05) (Figure). Serum HGF levels in the Edaravone group at 4 weeks seemed to be suppressed, but not be significantly when compared with the Control group (5.46 ± 0.55 ng/mL; P = .20) (Fig). Serum HGF levels might be the biomarker for postoperative intimal hyperplasia in the rat model, which can be suppressed with edaravone.