Effect of basic (FGF-2) and acidic (FGF-1) fibroblast growth factors on early haemopoietic cell development

Basic fibroblast growth factor (FGF-2) and acidic fibroblast growth factor (FGF-1) are mitogens for a variety of cell types. Many reports suggest that haemopoietic cells are among these. Nevertheless, when we examined the effect of recombinant human FGF-1 or 2 on normal human marrow cell proliferation in vitro , only minimal stimulatory activity could be detected. In this regard, the addition of either growth factor to cultures of ancillary cell depleted marrow mononuclear cells (MNC), or to highly enriched CD34⁺ MNC, failed to enhance haemopoietic colony number and induced only a slight increase in colony size. Perturbation of FGF receptor (FGF-R) expression on CD34⁺ MNC with antisense (AS) oligodeoxynucleotides (ODN) was also without apparent effect on cell growth. Neither could we demonstrate any effect of FGF-1 or 2 on survival of early progenitor cells in serum-free culture. To explain these findings, we examined progenitor cells for expression of the FGF-R at the mRNA and protein level using RT-PCR and flow cytometry. Primitive CD34⁺/KIT⁺ MNC had no detectable FGF-R (FGF-R1, 2, 3 or 4) mRNA or protein expression. In fact, direct immunofluorescence labelling of MNC for CD34 antigen and FGF-R1 demonstrated that expression of these markers was mutually exclusive in the populations examined. FGF-R1 expression was detected on subpopulations of MNC and on cells derived from day-6 CFU-GM and BFU-E colonies. Accordingly, FGF-R1 is either absent, or present at very low levels, on primitive haemopoietic cells. This fact, combined with our in vitro culture data, suggest that receptors are unlikely to play a significant role in the development of these early cells. Nevertheless, the development of mature cells may be influenced by the FGFs since the FGF-Rs are expressed on more mature cells.     

Role of vascular endothelial growth factor (VEGF) and placenta-derived growth factor (PlGF) in regulating human haemopoietic cell growth

Vascular endothelial growth factor (VEGF) and placental derived growth factor (PlGF) stimulate cell proliferation and differentiation by binding to their specific receptors, Flk-1/KDR and Flt-1 respectively. Flk-1/KDR-deficient murine embryos manifest failure of blood-island formation and vasculogenesis. The aim of this study was to directly evaluate the importance of VEGF, PlGF/Flt-1 and Flk-1/KDR receptor ligand interactions in regulating normal and malignant human haemopoiesis. Addition of VEGF and PlGF failed to enhance survival or cloning efficiency of human haemopoietic progenitors isolated from adult bone marrows, fetal livers or cord blood samples. This finding may be explained by the apparent absence of mRNA encoding Flt-1 and Flk-1/KDR receptors on stem cell rich CD34⁺ c-kit-R⁺ Rh123^low cells. Further studies revealed that Flt-1 R mRNA, but not Flk-1/KDR mRNA was first detectable in the more mature cells isolated from haemopoietic colonies. Accordingly, VEGF receptors are either absent, or expressed at very low level, on human haemopoietic stem/progenitor cells. Of interest, normal and malignant human haemopoietic cells appeared to secrete VEGF protein. However, in contrast to normal haemopoietic progenitors, VEGF co-stimulated HEL cell proliferation as well as CFU-GM colony formation from ∼15% of the chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) patients studied. Therefore, although VEGF appeared to have minimal effects on normal haemopoietic cell growth it would appear to drive malignant haemopoietic cell proliferation to some degree. Of more importance, however, we speculate that VEGF may play an very important role in leukaemogenesis by stimulating growth of vascular endothelium, thereby providing a sufficient blood supply to feed the growing haematological tumour.     

Gene expression of hepatocyte growth factor and its receptor in HCC and nontumorous liver tissues

ＭＥＴＨＯＤＳＧｅｎｅｅｘｐｒｅｓｓｉｏｎｏｆＨＧＦａｎｄＨＧＦｒｉｎ２６ｃａｓｅｓｏｆＨＣＣｔｉｓｓｕｅａｎｄｔｈｅｉｒａｄｊａｃｅｎｔｎｏｎｔｕｍｏｒｏｕｓｌｉｖｅｒｔｉｓｓｕｅｓｗａｓｄｅｔｅｒｍｉｎｅｄｗｉｔｈｄｉｇｏｘｉｇｅｎｉｎｌａ...     

Effect of hepatocyte growth factor on left ventricular remodeling after acute myocardial infarction in canine

Background and objectives To investigate the effect of hepatocyte growth factor (HGF) on left ventricular (LV) remodeling after acute myocardial infarction (AMI). Methods AMI was produced by ligation of proximal left anterior descending coronary artery(LAD) in 12 mongrel canines. These animals were randomized into 2 groups. In HGF group (n=6), canines were injected with pcDNA3-HGF lml (about 300ug) at the margin of infarcted myocardium; in control group (n=6) canines were injected with equal volume of normal saline. Cardiac function and left ventricular remodeling were evaluated with echocardiography at 1, 4, 8 weeks after MI. LV myocardium specimens were obtained at 8 weeks and stained with hematoxylin and eosin for histological examination or with sirius red to assess the collagen content. Results Compared with control group, LVEF in HGF group was significantly higher at 4 weeks (49.61+6.66 vs 39.84+6.39; P＜0.05) and at 8 weeks (51.57+8.53 vs 40.61+7.67; P＜0.05) after AMI, while LVESV was significantly lower in HGF group than that in control group at 8 weeks after AMI (18.98+3.47 vs 25.66+5.86; P＜0.05). Posterior left ventricular wall thickness decreased significantly from 1 wk to 8 wks after AMI in control group, while remained unchanged in HGF group. Compared with control group, histological examination showed more neovascularization and less scar, and sirius red staining indicated higher volume of type Ⅲ collagen (7.10±4.06% vs 3.77±1.09%; P＜0.05) and lower collagen Ⅰ/Ⅲ ratio value (1.11±0.52 vs 2.94±2.48; P＜0.05)in HGF group. Conclusion HGF gene transfer might improve cardiac function and LV remodeling after acute myocardial infarction by stimulating angiogenesis, reducing fibrosis, and reducing myocardial scarring.     

Involvement of growth factor receptor-bound protein-2 in rat hepatocyte growth

Growth factor receptor-bound protein-2 (GRB-2) is a protein linking receptor tyrosine kinase and Sos ( Son of Sevenless gene; Ras GDP/GTP exchange protein), leading to activation of the Ras-mitogen-activated protein kinase (MAPK) cascade. So far, it remains unclear how GRB-2 plays a role in signal transduction pathways evoked by hepatotrophic factors. This study was attempted to evaluate the involvement of GRB-2 in signalling in rat hepatocyte growth. Using rat cultured hepatocytes stimulated by hepatotrophic factors and regenerating livers after partial hepatectomy (PH) we examined GRB-2-mediated linkage of hepatotrophic factor receptors to signal transducing molecules such as Sos or dynamin-II by immunoprecipitation and western blot analysis. In primary cultured hepatocytes stimulated with hepatocyte growth factor (HGF) or epidermal growth factor (EGF), GRB-2 linked HGF receptor or EGF receptor, respectively, to Sos which activated the mitogen-activated protein kinase (MAPK) cascade. In contrast, in primary cultured hepatocytes stimulated with insulin, GRB-2 linked insulin receptor substrate-1 (IRS-1) to dynamin-II as well as Sos. In the early phase after PH, GRB-2 activated the Ras-MAPK cascade by linking HGF receptor, IRS-1, or EGF receptor to Sos. In the late phase after PH, a complex of IRS-1-GRB-2 associated with dynamin-II, indicating that GRB-2 may transduce signals from IRS-1 to dynamin-II. We conclude that GRB-2 may play a role in transmitting signals from hepatotrophic factors to not only MAPK but also to other signalling pathways in hepatocyte growth.     

Elevated serum concentrations of activated hepatocyte growth factor activator in patients with multiple myeloma

Objectives: Hepatocyte growth factor (HGF) is a potential key factor in multiple myeloma. Conversion of pro‐HGF to its active form is a critical limiting step for its biological effects. We aimed to examine the levels of the most potent activator, the hepatocyte growth factor activator (HGFA), in serum and bone marrow plasma of patients with multiple myeloma. Methods: The activated form of HGFA was measured by an enzyme‐linked immunosorbent assay in serum (n = 49) and bone marrow plasma (n = 16) from multiple myeloma patients, and in serum from healthy controls (n = 24). Results: The median concentrations of activated HGFA in myeloma and control sera were 39.7 (range 6.2–450.0) and 17.6 ng/mL (range 4.8–280.6), respectively. The difference was statistically significant (P = 0.037). The median concentration of activated HGFA in bone marrow plasma was 6.1 ng/mL (range 3.5–30.0). Conclusion: We here show for the first time that the activated form of HGFA is present at high levels in serum and bone marrow of myeloma patients, thus providing a necessary prerequisite for the activation of HGF.     

Plasma human hepatocyte growth factor concentrations in patients with biliary obstruction

BACKGROUND: It has been suggested that human hepatocyte growth factor (hHGF) maintains the growth and viability of hepatocytes and biliary epithelial cells. The purpose of this study was to determine plasma hHGF concentrations in patients with obstructive jaundice and to correlate these findings with clinical outcome. METHODS: The study included 22 patients who had biliary obstruction and underwent percutaneous transhepatic biliary drainage. The plasma concentrations of hHGF, standard liver function tests, daily bile flow and the half-life of serum total bilirubin were measured following the drainage. RESULTS: Plasma hHGF concentrations were significantly higher in patients with biliary obstruction compared with a control group (P<0.01). The plasma hHGF concentrations correlated with white cell count, prothrombin time and bilirubin half-life (P<0.05), but not with the values from other liver function tests. Seven patients who died within 3 months after biliary drainage had significantly higher concentrations of plasma hHGF than the 15 patients who survived for at least 3 months (P<0.05). The patients who experienced a poor outcome also had lower bile flows and prolonged bilirubin half-lives compared with the survivors (P<0.05). The plasma hHGF concentrations decreased significantly after biliary drainage in the survivors (P<0.01), but not in the patients with a poor outcome. CONCLUSIONS: These results suggest that systemic inflammation and the hepatic dysfunction caused by obstructive jaundice cause an increase in the plasma concentrations of hHGF. In addition, the plasma concentrations of hHGF may be a predictor of poor outcome in jaundiced patients.     

Clinical significance of vascular endothelial growth factor and hepatocyte growth factor in multiple myeloma

Angiogenesis is a crucial process in the progression of multiple myeloma (MM). Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are multifunctional cytokines that potently stimulate angiogenesis including tumour neovascularization. Serum levels of VEGF and HGF were measured in 52 patients with MM by enzyme-linked immunosorbent assay (ELISA). Serum levels of VEGF and HGF were elevated in MM patients compared with healthy controls (VEGF: mean 0.31 ng/ml and 0.08 ng/ml respectively, P < 0.01; HGF: mean 2.17 ng/ml and 0.45 ng/ml, respectively, P < 0.001). In serial samples taken after chemotherapy, serum VEGF and HGF levels were correlated with M-protein levels. Serum levels of VEGF were higher in patients with extramedullary plasmacytomas than in patients without them (P < 0.05). They were also significantly higher in a group of patients who showed poor response to chemotherapy (P < 0.01). Serum levels of HGF were higher in patients with complications such as anaemia, hypercalcaemia and amyloidosis than in patients without these complications (P < 0.01, P < 0.05, P < 0.05 respectively). Both serum VEGF and HGF levels were significant predictors of mortality (P = 0.01, P = 0.02, respectively, log-rank test). The present study demonstrated that serum levels of VEGF and HGF are significantly elevated and dependent on the severity of MM, suggesting that measurement of VEGF and HGF may be useful for assessing disease progression and for predicting the response to chemotherapy in MM patients.     

反义核苷酸干预血管成形术后平滑肌细胞生长因子基因表达的研究

为了研究反义核苷酸对平滑肌细胞（ＳＭＣ）及生长因子基因表达的影响。本实验对兔髂动脉粥样硬化模型行血管成形术；应用Ｎｏｒｔｈｅｒｎ印迹杂交和ＲＴ－ＰＣＲ方法观察反义核苷酸对体外兔髂动脉ＳＭＣ增殖及转化生长因子－β１（ＴＧＦ－β１）、表皮生长因子受体（ＥＧＦＲ）、碱性成纤维细胞生长因子（ｂＦＧＦ）基因表达的影响。结果表明：反义核苷酸抑制ＳＭＣ增生，并呈浓度依赖性；反义核苷酸抑制ＴＧＦ－β１和ｂＦＧＦｍＲＮＡ表达；阳离子脂质体能明显增强反义核苷酸的上述作用。在培养的兔髂动脉ＳＭＣ中ＥＧＦＲｍＲＮＡ表达阴性。结论：反义核苷酸抑制兔髂动脉ＳＭＣ增生与抑制ＴＧＦ－β１和ｂＦＧＦｍＲＮＡ表达有密切关系。     

Elevation of serum hepatocyte growth factor during granulocyte colony-stimulating factor-induced peripheral blood stem cell mobilization

We examined serum levels of the angiogenic factors, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF), in normal donors for allogeneic peripheral blood stem cell (PBSC) transplantation. Granulocyte colony-stimulating factor (G-CSF) (filgrastim 400 microg/m2/d) was administered to 23 donors for 5 d and aphereses were performed on days 4 and 5. Although bFGF remained at similar levels after G-CSF treatment, serum VEGF and HGF levels increased 1.5-fold (n = 13; P = 0.02) and 6.8-fold (n = 23; P < 0.0001) respectively. The serum HGF level before G-CSF administration on day 1 correlated inversely with mobilized CD34+ cell numbers. Time course kinetics of HGF showed that on the day after G-CSF administration (day 2), serum HGF levels increased to 3678 pg/ml. For auto PBSC mobilization with chemotherapy and G-CSF 200 microg/m2/d (n = 8), we observed similar HGF elevation, which appeared to be dose-dependent on the G-CSF administered.     

Protective effect of non-mitogenic human acidic fibroblast growth factor on hepatocyte injury

Aim: To study whether non-mitogenic human acidic fibroblast growth factor (nm-haFGF) has protective effects on H(2)O(2)-induced hepatocyte injury in vitro and CCl(4)-induced hepatocyte injury in vivo. Methods: (i) HL-7702 hepatocytes were incubated with different concentrations of nm-haFGF for 12 h, and then the activity of lactate dehydrogenase (LDH) in culture medium was detected, and genomic DNA electrophoresis analysis was observed after being exposed to H(2)O(2) (8 mmol/L) for 4 h. Proximately, apoptotic rates and protein expressions of Bcl-2 and Bax of HL-7702 cell were detected after being exposed to H(2)O(2) (0.2 mmol/L) for 20 h. (ii) Being injected intraperitoneally with nm-haFGF, mice were treated with CCl(4) intraperitoneally to induce hepatic injury. Twenty-four hours later, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured and histopathologic changes were evaluated. Results: (i) In vitro tests: LDH activities and apoptotic rates decreased, the protein expression of Bcl-2 increased and Baxdecreased in nm-haFGF-treated groups at the concentrations of 100 150 and 200 ng/mL, compared with that in the model control group, which was treated with H(2)O(2) alone. The genomic DNA remained nearly intact at the concentrations of 150 and 200 ng/mL. (ii) In vivo tests: serum ALT and AST in nm-haFGF-treated groups (10 mug/kg and 20 mug/kg) were much lower as compared to the model control group, which was treated with CCl(4) alone. Histological examination showed that nm-haFGF markedly ameliorated hepatocytes vacuolation, cloudy swelling and inflammatory cells infiltration induced by CCl(4). Conclusion: nm-haFGF had protective effects against H(2)O(2)-induced hepatocyte injury in vitro and CCl(4)-induced acute liver injury in vivo.     

气道内滴注肝细胞生长因子对野百合碱诱导肺动脉高压大鼠的干预研究

目的 通过气道内滴注腺病毒转染肝细胞生长因子（adenovirus hepatocyte growth factor,Ad-HGF）干预野百合碱（monocrotaline,MCT）诱导的肺动脉高压（pulmonary hypertension,PAH）模型大鼠,观察Ad-HGF干预对平均肺动脉压（mean pulmonary artery pressure,mPAP）等指标的影响.方法 选用健康雄性SD大鼠40只,随机[采用随机单位（区）组设计方法]分为4组：正常对照组（normal,NOR组）10只,MCT诱导PAH组（PAH组）10只、单次和重复肝细胞生长因子（hepatocyte growth factor,HGF）干预治疗组（HGF和THGF组）各10只.NOR组和PAH组：气道内滴注0.2 mL磷酸盐缓冲液;HGF组和THGF组：气道内滴注0.2 mL Ad-HGF 1次和一周后重复一次共2次.再饲养两周后,测定各组大鼠的肺动脉压,计算右心室肥厚指数;苏木素伊红染色观察肺动脉管壁等;酶联免疫吸附（ELISA）法测定肺组织匀浆中HGF浓度.结果 与PAH组大鼠比较,HGF组和THGF组大鼠的mPAP、右心室肥厚指数、肺动脉管壁指数和面积指数明显降低,肺苏木素伊红染色肺小动脉管壁厚度减少,管腔面积增大,血管周围炎症细胞浸润减轻,肺组织匀浆HGF浓度明显升高,差异有统计学意义（P＜0.05）,且低于NOR组水平.结论 经气道内滴注转染Ad-HGF,能明显降低但不能完全逆转MCT诱导PAH大鼠的mPAP,减少肺小动脉管壁厚度,减轻右心室肥厚程度,从而达到延缓PAH进程的作用.     

肝细胞生长因子对犬急性心肌梗死后左心室重构的影响

目的探讨肝细胞生长因子(hepatocyte growth factor,HGF)对急性心肌梗死后左心室重构的影响。方法将12只杂种犬结扎左冠状动脉前降支,复制急性心肌梗死模型,随机分为2组:对照组和治疗组,每组6只。治疗组于梗死心肌周围注射pc-DNA3-HGF基因1 ml,对照组给予等量的生理盐水。分别于术后1、4、8周进行超声心动图检查,检测心功能、左心室重构指标。术后8周取心肌组织行HE染色及天狼猩红染色,图像分析系统测定Ⅰ、Ⅲ型胶原含量。结果术后4周时,治疗组左心室射血分数(LVEF)明显高于对照组(P<0.05)。8周时,LVEF明显升高,左心室舒张末容积较对照组降低(P<0.05)。对照组组内比较显示左心室后壁厚度显著降低(P=0.04)。HE染色可观察到治疗组梗死心肌周围毛细血管较对照组增多,而对照组瘢痕形成明显。天狼猩红染色显示治疗组Ⅲ型胶原含量高于对照组,Ⅰ/Ⅲ型胶原比例低于对照组(P<0.05)。结论HGF可能通过减少胶原的沉积及促进血管增生,减少心肌坏死及瘢痕形成,从而改善心功能及急性心肌梗死后的左心室重构。     

Elevated serum concentrations of hepatocyte growth factor in acute myelocytic leukaemia

Serum concentrations of hepatocyte growth factor (HGF) were measured in 60 patients suffering from acute myelocytic leukaemia (AML). At the time of diagnosis elevated HGF concentrations (> 1.25 ng/ml) were found in 28% of the patients. HGF levels correlated with the presence of disseminated intravascular coagulation (DIC), levels of lysozyme, creatinine, peripheral blood blast counts and lactic dehydrogenase. In the group of patients with high HGF (>1.25 ng/ml) we found a tendency towards an increased early mortality; 41% of them died within 15 d from diagnosis, as opposed to 5% of the patients with normal HGF (log rank test p=0.07). DIC-related bleeding or thrombosis contributed to this early mortality. In responders, HGF levels normalized after treatment. HGF levels are low in neutropenia and neutropenic infections.     

Plasma hepatocyte growth factor is a novel marker of AL cardiac amyloidosis

Abstract

Background: Cardiac amyloidosis is an infiltrative cardiomyopathy that is challenging to diagnose. We hypothesized that the novel biomarkers hepatocyte growth factor (HGF), galectin-3 (GAL-3), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) would be elevated in cardiac amyloidosis and may be able to discriminate from non-cardiac systemic amyloidosis or other cardiomyopathies with similar clinical or morphologic characteristics.

Methods: Patients were selected from the Vanderbilt Main Heart Registry according to the following groups: (1) amyloid light-chain (AL) cardiac amyloidosis (n?=?26); (2) transthyretin (ATTR) cardiac amyloidosis (n?=?7); (3) left ventricular hypertrophy (LVH) (n?=?45); (4) systolic heart failure (n?=?42); and (5) non-cardiac systemic amyloidosis (n?=?7). Biomarkers were measured in stored plasma samples. Biomarkers' discrimination performance in predicting AL cardiac amyloidosis (i.e., Concordance index) was reported. A survival analysis was used to explore the relationship between HGF levels and mortality among AL cardiac amyloidosis patients.

Results: HGF levels were markedly elevated in patients with AL cardiac amyloidosis (median?=?622, interquartile range (IQR): 299–1228?pg/mL) compared with the other groups, including those with non-cardiac systemic amyloidosis (median?=?134, IQR: 94–163?pg/mL, p?<?0.001). HGF was not a specific marker for ATTR amyloidosis. Gal-3 was elevated in all groups with amyloidosis but could not differentiate between those with and without cardiac involvement. There was no difference in IL-6 or VEGF between those with AL cardiac amyloidosis compared to other groups (p?=?0.13 and 0.057, respectively).

Conclusions: HGF may be a specific marker that distinguishes AL cardiac amyloidosis from other cardiomyopathies with similar clinical or morphologic characteristics. Further studies are necessary to determine whether HGF levels predict the likelihood of survival.     

急性血栓性肺栓塞兔血清肝细胞生长因子的变化及其意义

目的:观察急性血栓性肺栓塞(acute pulmonary thromboembolism ,PTE)兔血清中肝细胞生长因子(hepatocyte growth factor, HGF)的变化特征,并探讨其对PTE的早期诊断价值.方法:新西兰纯种白兔16只,随机均分为对照组和模型组;模型组采用自体血栓回输法建立PTE模型,对照组以等量0.9%氯化钠溶液代替.分别在0、1、3、6、12、24、48、72 h采集血样,ELISA法检测HGF及IL-1β含量.结果:模型组血HGF水平于1 h后开始升高[(0.853±0.317)μg/L],持续升高到3 h略降低后又继续升高,12 h升高最明显[(1.742±0.487)μg/L],在48 h仍保持高水平,72 h开始回落;对照组各时间点血HGF水平均无明显变化,一直保持在较低水平;模型组在1、3、6、12、24、48、72 h血清HGF水平均显著高于对照组(P<0.05～0.01).模型组血IL-1β于0 h后开始升高,在3 h达到峰值(0.181 μg/L),6 h降至较低水平(0.09 μg/L),直至72 h无明显变化;对照组始终在<0.089 μg/L水平.结论: HGF有望作为一种新的生物学标记物用于PTE早期诊断.     

EflFect of hepatocyte growth factor on left ventricular remodeling after acute myocardial infarction in canine

Background and objectives To investigate the effect of hepatocyte growth factor (HGF) on left ventricular (LV) remodeling after acute myocardial infarction (AMI). Methods AMI was produced by ligation of proximal left anterior descending coronary artery (LAD) in 12 mongrel canines. These animals were randomized into 2 groups. In HGF group (n=6), canines were injected with pc-DNA3-HGF 1 ml (about 300ug) at the margin of infarcted myocardium; in control group (n=6) canines were injected with equal volume of normal saline. Cardiac function and left ventricular remodeling were evaluated with echocardiography at 1,4, 8 weeks after MI. LV myocardium specimens were obtained at 8 weeks and stained with hematoxylin and eosin for histological examination or with sirius red to assess the collagen content. Results Compared with control group, LVEF in HGF group was significantly higher at 4 weeks (49.61 6.66 vs 39.84 6.39; P<0.05) and at 8 weeks (51.57 8.53 vs 40.61 7.67; P<0.05) after AMI, while LVESV was significantly lower in HGF group than that in control group at 8 weeks after AMI (18.98 3.47 vs 25.66 5.86; P<0.05). Posterior left ventricular wall thickness decreased significantly from 1 wk to 8 wks after AMI in control group, while remained unchanged in HGF group.Compared with control group, histological examination showed more neovascularization and less scar, and sirius red staining indicated higher volume of typeⅢcollagen (7.10±4.06% vs 3.77±1.09%; P<0.05) and lower collagenⅠ/Ⅲratio value (1.11±0.52 vs 2.94±2.48; P<0.05) in HGF group. Conclusion HGF gene transfer might improve cardiac function and LV remodeling after acute myocardial infarction by stimulating angiogenesis, reducing fibrosis, and reducing myocardial scarring.