PMID- 29382231 OWN - NLM STAT- MEDLINE DCOM- 20190624 LR - 20190624 IS - 1557-7422 (Electronic) IS - 1043-0342 (Linking) VI - 29 IP - 7 DP - 2018 Jul TI - Overexpression of Hepatocyte Growth Factor mRNA Induced by Gene Transfer Attenuates Neointimal Hyperplasia After Balloon Injury. PG - 816-827 LID - 10.1089/hum.2017.173 [doi] AB - Hepatic growth factor (HGF) has been widely used in studies on arterial remodeling after injury, and results turn out to be inconsistent. The changes of endogenous HGF expression after injury also remain controversial. This study clarified the role of exogenous human HGF (hHGF) gene transfer in neointimal hyperplasia and investigated the associated alterations of endogenous HGF and c-Met expressions under endothelial denudation with or without hHGF gene transfer using a balloon-injured rabbit aorta model. Sixty-one rabbits were randomly divided into normal controls, endothelial injury, endothelial injury with hHGF, or the control vector gene transfer groups. On weeks 1, 2, 4, and 8 after injury, neointimal hyperplasia and endothelialization were evaluated by the ratio of neointimal area to medial area (N/M ratio), CD31-positive staining, alpha-smooth muscle actin, and endothelial nitric oxide synthase expressions using histological analysis, immunohistochemistry staining, or real-time quantitative reverse transcriptase polymerase chain reaction. Endogenous rabbit HGF (rHGF) and c-Met expressions were detected with immunohistochemistry staining and quantitative reverse transcriptase polymerase chain reaction. It was found that expressions of endogeneous rHGF and c-Met in endothelial injury upregulated with peak levels on week 2 or week 4 after injury (p < 0.01). On week 1 after hHGF transfer, neointimal hyperplasia was significantly inhibited (p < 0.001), with decreased alpha-smooth muscle actin expression (p < 0.05) and improved endothelial cells regeneration and function (p < 0.01). More remarkable overexpression of endogenous rHGF and c-Met mRNAs were detected, and lowered positive staining of rHGF and c-Met was shown in the neointima (p < 0.05). These results demonstrated hHGF gene transfer induced further overexpression of endogenous rHGF and c-Met mRNAs but lowered immunoreactivities of rHGF and c-Met in the neointima, thus leading to significant attenuation of neointimal hyperplasia. FAU - He, Yu AU - He Y AD - 1 Department of Ultrasound, China-Japan Union Hospital of Jilin University , Changchun, China. FAU - Mei, Li AU - Mei L AD - 2 Department of Ultrasound, the First Hospital of Jilin University , Changchun, China . FAU - Jin, Ying AU - Jin Y AD - 3 Department of Surgery, the First Hospital of Jilin University , Changchun, China . FAU - Li, Xiao-Ping AU - Li XP AD - 1 Department of Ultrasound, China-Japan Union Hospital of Jilin University , Changchun, China. FAU - Jin, Chunxiang AU - Jin C AD - 1 Department of Ultrasound, China-Japan Union Hospital of Jilin University , Changchun, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180314 PL - United States TA - Hum Gene Ther JT - Human gene therapy JID - 9008950 RN - 0 (Actins) RN - 0 (HGF protein, human) RN - 0 (RNA, Messenger) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Actins/genetics MH - Animals MH - Endothelial Cells/drug effects/metabolism MH - Gene Expression Regulation/genetics MH - *Genetic Therapy MH - Genetic Vectors/administration & dosage MH - Hepatocyte Growth Factor/*administration & dosage/genetics MH - Humans MH - Hyperplasia/genetics/pathology/*therapy MH - Neointima/genetics/pathology/*therapy MH - Proto-Oncogene Proteins c-met/*genetics MH - RNA, Messenger/genetics MH - Rabbits OTO - NOTNLM OT - balloon injury OT - gene transfer OT - hepatocyte growth factor (HGF) OT - neointimal hyperplasia OT - overexpression EDAT- 2018/02/01 06:00 MHDA- 2019/06/25 06:00 CRDT- 2018/02/01 06:00 PHST- 2018/02/01 06:00 [pubmed] PHST- 2019/06/25 06:00 [medline] PHST- 2018/02/01 06:00 [entrez] AID - 10.1089/hum.2017.173 [doi] PST - ppublish SO - Hum Gene Ther. 2018 Jul;29(7):816-827. doi: 10.1089/hum.2017.173. Epub 2018 Mar 14.