Abstract
Objectives. To verify the relationship between Egr-1 and vein graft restenosis and investigate the related mechanisms. Methods. Mouse vein graft models were established in Egr-1 knockout (KO) and wild-type (WT) mice. The vein grafts in the mice were taken for pathological examination and immunohistochemical analysis. The endothelial cells (ECs) were stimulated by using a computer-controlled cyclic stress unit. BrdU staining and PCR were used to detect ECs proliferation activity and Egr-1 and ICAM-1 mRNA expression, respectively. Western-blot analysis was also used to detect expression of Egr-1 and intercellular adhesion molecule-1 (ICAM-1) proteins. Results. The lumens of vein grafts in Egr-1 KO mice were wider than in WT mice. ECs proliferation after mechanical stretch stimulation was suppressed by Egr-1 knockout (P < 0.05). Both in vein grafts and ECs from WT mice after mechanical stretch stimulation, mRNA expression and protein of Egr-1 and ICAM-1 showed increases (P < 0.05). However, ICAM-1 expression was significantly suppressed in ECs from Egr-1 knockout mice (P < 0.05). Conclusions. Egr-1 may promote ECs proliferation and result in vein graft restenosis by upregulating the expression of ICAM-1. As a key factor of vein graft restenosis, it could be a target for the prevention of restenosis after CABG surgery.
Highlights
Coronary artery bypass graft (CABG) is one of the most effective therapies for coronary artery diseases (CAD)
Our preliminary study showed that Early growth response protein 1 (Egr-1) is closely related with restenosis, and the degree of vein graft stenosis in Egr-1 knockout (KO) mice was significantly lower than that in wild-type (WT) mice, indicating that Egr-1 could promote vein graft stenosis
Egr-1 KO mice were used as donors, and littermate Egr-1 KO mice were used as recipients
Summary
Coronary artery bypass graft (CABG) is one of the most effective therapies for coronary artery diseases (CAD). After CABG, vein grafts walls sustain a blood pressure that is much higher than the usual venous pressure, and the walls of the vein graft are often injured by pulsatile stretching [4,5,6] These stresses lead to endothelial dysfunction, which is the initial factor inducing the proliferative thickening of the intima [7]. Activated ECs and SMCs produce a number of attracting chemokines, recruiting and retaining monocytes into the endothelium and the extracellular matrix, where they transform into macrophages participating to atherosclerotic plaque development [9, 10] Together, these three mechanisms are involved in the proliferative thickening of the intima and, in CABG failure [11, 12]
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