PMID- 29130662 OWN - NLM STAT- MEDLINE DCOM- 20190530 LR - 20190530 IS - 1672-173X (Print) IS - 1672-173X (Linking) VI - 48 IP - 5 DP - 2017 Sep TI - [The Role of Bone Morphogenic Protein-4 in the Progression of Vein Graft Hyperplastic Remodeling under Hyperglycemic Condition]. PG - 710-715 AB - OBJECTIVE: This study was designed to assess the vessel wall characteristics and the expression levels of bone morphogenic protein4(BMP4) and proliferating cell antigen Ki67 in vein grafts harvested from diabetic rats,and to investigate the role of BMP4 in progression of vein graft hyperplastic remodeling under hyperglycemic condition. METHODS: 48 male SpragueDawky rats [body mass (194+/-16) g] aged 8 weeks were randomly divided into diabetes mellitus (DM) group ( n=24) and nondiabetes mellitus (NDM) group ( n=24). The DM rats were induced by streptozotocin in combination with highsugar and highfat diet. The unilateral external jugular vein was interposition grafted into the common carotid arteries in the two groups. The vein grafts were harvested at preoperatively and 1,2 and 4 weeks postoperatively ( n=6) in each group. The morphological characteristics of the venous graft wall were evaluated by hematoxylineosin staining,and the expression levels and the distribution of Ki67 and BMP4 were assessed by immunohistochemistry analysis,then the expression of BMP4 gene and protein was measured by realtime polymerase chain reaction (RTPCR) and Western blot assay respectively. RESULTS: In the progression of rats vein grafts hyperplastic remodeling,the venous wall thickness of rats thickened with time increasing,and the intimal and medial thickness of the vein grafts harvested from DM rats were significantly higher than those from NDM rats at the same time postoperatively ( P<0.05). Ki-67 was highly xpressed in smooth muscle cells nucleus located in the rats vein grafts,and its expression level was up-regulated gradually in the progression of vein graft failure,and the Ki 67 positive cells of vein grafts from DM rats were significantly higher than those from NDM controls at the same period ( P<0.05). Immunohistochemistry analysis showed that BMP4 was expressed in smooth muscle cells cytoplasmof the rats vein grafts,combined with the results of RT-PCR and Western blot assay,there was a little BMP4 expression could be seen in venous wall of NDM rats,while BMP4 positive cells and the expression level of BMP4 gene and protein from DM rats vein grafts was increasing with obvious time dependence and significantly higher than the NDM rats ( P<0.05). CONCLUSION: The morphological and pathological changes within the venous wall were significantly correlated with the high expression levels of BMP4 in vein grafts harvested from diabetic rats,implying a potential role of BMP4 in the progression of accelerated vein graft failure under hyperglycemic condition. FAU - Fang, Deng-Feng AU - Fang DF AD - Department of Anesthesiology,West China Hospital,Sichuan University,Chengdu 610041,China. FAU - Zhang, Hong-Wei AU - Zhang HW AD - Department of Cardiovascular Surgery,West China Hospital,Sichuan University,Chengdu 610041,China. FAU - Gu, Jun AU - Gu J AD - Department of Cardiovascular Surgery,West China Hospital,Sichuan University,Chengdu 610041,China. FAU - Fan, Kang-Jun AU - Fan KJ AD - Department of Cardiovascular Surgery,West China Hospital,Sichuan University,Chengdu 610041,China. FAU - Liang, Huai-Min AU - Liang HM AD - Department of Cardiovascular Surgery,West China Hospital,Sichuan University,Chengdu 610041,China. FAU - Shen, Jia-Yu AU - Shen JY AD - Department of Cardiovascular Surgery,West China Hospital,Sichuan University,Chengdu 610041,China. FAU - Zhang, Er-Yong AU - Zhang EY AD - Department of Cardiovascular Surgery,West China Hospital,Sichuan University,Chengdu 610041,China. FAU - Hu, Jia AU - Hu J AD - Department of Cardiovascular Surgery,West China Hospital,Sichuan University,Chengdu 610041,China. LA - chi PT - Journal Article PL - China TA - Sichuan Da Xue Xue Bao Yi Xue Ban JT - Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition JID - 101162609 RN - 0 (Bmp4 protein, rat) RN - 0 (Bone Morphogenetic Protein 4) RN - 0 (Ki-67 Antigen) SB - IM MH - Animals MH - Bone Morphogenetic Protein 4/*metabolism MH - Diabetes Mellitus, Experimental/*metabolism MH - Hyperplasia MH - Jugular Veins/*transplantation MH - Ki-67 Antigen/metabolism MH - Male MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - *Vascular Remodeling OTO - NOTNLM OT - Bone morphogenic protein-4 OT - Coronary artery bypass graft OT - Hyperglycemic condition OT - Vein grafts EDAT- 2017/11/14 06:00 MHDA- 2019/05/31 06:00 CRDT- 2017/11/14 06:00 PHST- 2017/11/14 06:00 [entrez] PHST- 2017/11/14 06:00 [pubmed] PHST- 2019/05/31 06:00 [medline] PST - ppublish SO - Sichuan Da Xue Xue Bao Yi Xue Ban. 2017 Sep;48(5):710-715.