[Expression of early growth response gene-1 and its correlative genes in autogenous vein graft and significance thereof: an experiment with rats].
OBJECTIVE
To investigate the expression of early growth response gene-1 (Egr-1) and its correlative genes: platelet-derived growth factor-B (PDGF-B) gene and transforming growth factor-beta(1) (TGF-beta(1)) gene, in autogenous vein graft and the relationship of the expression of these genes to intimal hyperplasia (IH).


METHODS
A segment of the right common jugular vein was transplanted to the infra-renal abdominal aorta of the same individual so as to establish an autogenous vein graft model in 90 Wistar rats. Vein samples were harvested 1, 2, 6, and 24 hours, 3 and 7 days, and 2, 4, and 6 weeks after the operation to undergo histological examination. In situ hybridization and RT-OCR were performed to examine the mRNA expression of Egr-1, PDGF-B, and TGF-beta(1). Western blotting and immunohistochemistry were used to detect the protein expression of Egr-1, PDGF-B, and TGF-beta(1). The contralateral common jugular vein was used as control.


RESULTS
Histological examination showed a great amount of vascular smooth muscle cells (VSMCs) in the tunica intima and tunica media of the vein graft since the 7 th day after the transplantation. mRNA expression of Egr-1, PDGF-B, and TGF-beta(1) was not found in the normal veins. The expression of Egr-1 mRNA in the vein graft showed a biphasic manner: increased remarkably 1 h after the transplantation, decreased during the period 6 h approximately 3 d after, re-increased 7 d after, and peaked 4 weeks after. The mRNA expression of PDGF-B appeared 6 h after, and peaked 2 weeks after, and began to decrease since the 4 th week. The mRNA expression of TGF-beta(1) increased 6 h after, peaked 7d after, and began to decrease 2 weeks after. The protein expression of Egr-1 appeared 2 h after, and peaked 4 weeks after; the protein expression of PDGF-B appeared 6 h after and peaked 4 weeks after; and the protein expression of TGF-beta(1). Appeared 24 h after and peaked 2 weeks after. Immunohistochemistry showed that Egr-1 protein expression was mainly in the VSMCs and monocytes/macrophages in the tunica media in the early stage after transplantation, and peaked 4 weeks later with a positive cell rate of 40% +/- 9%; in the early stage after transplantation PDGF-B protein expression was mainly in the VSMCs in the tunica media, and peaked 4 weeks after with a positive cell rate of 45% +/- 4%; the TGF-beta(1) protein expression peaked 2 weeks after with a positive cell rate of 41% +/- 7%; and 4 weeks after transplantation the protein expressions of Egr-1, PDGF-B, and TGF-beta(1) were all mainly in the VSMCs in the newly-grown tunica intima.


CONCLUSIONS
The IH of vein graft is affinitive with the expression of Egr-1, PDGF-B, and TGF-beta(1). The activation and expression of Egr-1, PDGF-B, and TGF-beta(1) depend on Egr-1 and may contribute to the high expression of Egr1 via a feedback mechanism.
Liu
Cheng-wei
CW
Department of Vascular Surgery, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
Hu
Xin-hua
XH
Yang
Jun
J
Zhang
Qiang
Q
Zhang
Xue-song
XS
Duan
Zhi-quan
ZQ
D000818:Animals; D015153:Blotting, Western; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006083:Graft Occlusion, Vascular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006965:Hyperplasia; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D014182:Transplantation, Autologous; D017539:Tunica Intima / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D014680:Veins / Q000637:transplantation*
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta