原发性高血压患者血清肝细胞生长因子的测定

目的 :肝细胞生长因子 (HGF)是一种特异性内皮生长因子 ,参与血管内皮损伤修复过程。高血压引起的血管内皮细胞损伤也可能导致HGF异常 ,为研究这一可能性 ,本项目测定无肝肾功能损伤及其他并发症的原发性高血压患者及正常对照者的血清HGF浓度。方法 :18例男性高血压患者及 13例男性正常对照者入选。所有受试者停药二周。血清HGF浓度用酶联免疫分析法(ELISA)测定。结果 :正常对照组血清HGF浓度为 0 32 1± 0 12 5ng/ml;原发性高血压组为 0 36 8± 0 2 6 9ng/ml,二组之间无显著性差异 (P >0 0 5 )。收缩压 ,舒张压及平均动脉压与血清HGF水平无相关性。结论 :血清HGF在轻 ,中度原发性高血压患者中并不增高。高血压引起血管内皮细胞损伤时 ,虽然局部HGF迅速产生 ,但循环HGF并不受影响。     

血管内皮生长因子与冠状动脉粥样硬化及侧枝循环形成的关系

探讨血管内皮生长因子与冠状动脉粥样硬化狭窄程度及冠状动脉侧枝循环形成的关系 ,应用酶联免疫吸附法检测 10 2例经冠状动脉造影确诊的冠心病患者和 43例冠状动脉造影正常者的冠状动脉血浆血管内皮生长因子浓度 ,作冠状动脉病变Leaman记分和侧枝循环Rentrop分级 ,并分析血管内皮生长因子与其的关系。结果发现 ,冠心病患者冠状动脉血浆血管内皮生长因子平均浓度明显高于正常对照组 ( 2 2 5± 147ng L比 74± 5 2ng L ,P <0 .0 1) ,而且冠心病患者中侧枝循环形成者血管内皮生长因子平均浓度明显高于无侧枝循环形成者 ( 2 99± 15 2ng L比 2 0 2± 12 2ng L ,P <0 .0 5 ) ;血浆血管内皮生长因子浓度与Leaman记分呈显著正相关 (r=0 .693 ,P <0 .0 0 1)。结果提示 ,血管内皮生长因子与冠状动脉粥样硬化狭窄程度及冠状动脉侧枝循环形成具有一定的关系 ,血管内皮生长因子可能既有促进冠状动脉侧枝循环形成的作用 ,又在动脉粥样硬化发展中起到一定的双重调节作用     

吸烟对男性血管内皮生长因子水平的影响

目的 探讨吸烟对吸烟者体内血管内皮生长因子水平的影响,进一步探讨吸烟是否影响动脉粥样硬化的形成与发展.方法 从2006年4～6月到我院体检中心体检的对象中随机抽取86名符合纳入标准的为研究对象,均为男性,且排除高血压、糖尿病、近两周有严重的感染性疾病、自身免疫性疾病、恶性肿瘤以及严重的心、肾及肝病和血液系统疾病.按照WHO(1984)关于吸烟调查标准方法的建议,吸烟者需每天吸烟1支以上,持续吸烟1年以上,并用吸烟指数(＝每天吸烟量×吸烟年数)来反映吸烟的程度.根据这个标准86人中有吸烟组48人,对照组38人.所有研究对象于调查当日清晨空腹采集静脉血5 mL,静置20 min后取上清液保存于-20℃冰箱待测.血清血管内皮生长因子采用酶联免疫吸附法检测,试剂盒购于北京中杉金桥试剂公司(进口分装),按操作说明书操作,并将检测结果与吸烟指数进行相关分析.结果 两组年龄分别为吸烟组39.62±6.74岁;对照组41.21±8.38岁;两组比较差异无统计学意义(P＞0.05).吸烟组血清血管内皮生长因子为376.2±23.1 ng/L,对照组为307.9±19.7 ng/L;两组比较,吸烟者血清血管内皮生长因子浓度明显高于不吸烟的对照者,差异有极显著统计学意义(P＜0.01).经相关分析发现,血清血管内皮生长因子浓度与吸烟指数无相关性(r=0.31,P＞0.05).结论 吸烟者血清血管内皮生长因子浓度高于不吸烟者,且与吸烟程度无相关性.血清血管内皮生长因子浓度升高可能是吸烟者易患心脑血管疾病的因素之一.     

血清肝细胞生长因子与高血压患者合并急性冠脉综合征的相关性

目的 探讨肝细胞生长因子（HGF）在原发性高血压及急性冠脉综合征（ACS）患者血清中的表达水平及其临床意义.方法 采用双抗体夹心酶联免疫荧光吸附法（ELISE）测定25例单纯高血压患者、20例高血压合并不稳定型心绞痛（UA）患者、25例高血压合并急性心肌梗死（AMI）患者、25名健康者的HGF血清浓度.结果 单纯高血压组、高血压合并UA组和高血压合并AMI组血清HGF浓度较正常对照组明显高,差异有统计学意义（P＜0.01）;高血压合并UA组、高血压合并AMI组血清HGF浓度较单纯高血压组明显高,差异有统计学意义（P＜0.05）;高血压合并AMI组血清HGF浓度较高血压合并UA组明显高,差异有统计学意义（P＜0.05）.结论 高浓度的HGF与血管内皮损伤和修复以及不稳定的粥样斑块破裂有关.测定HGF浓度将成为早期诊断高血压及其分级的重要指标和早期筛查不稳定冠状动脉粥样硬化斑块的新手段.     

血清肝细胞生长因子测定对急性冠脉综合征患者的临床意义

目的探讨急性冠脉综合征(ACS)患者血清肝细胞生长因子(HGF)水平变化的临床意义。方法入选59例ACS患者(急性心肌梗死组n=36,发病12h以内;不稳定型心绞痛组n=23)于入院时肝素注射前取静脉血,通过酶联免疫法测定血清HGF浓度。同时对与之性别及年龄相匹配的27例正常人测定相同指标。结果血清HGF浓度在AMI组[(1572.9±229.0)pg/ml]、UAP组[(899.2±63.9)pg/ml]较正常对照组[(619.5±31.1)pg/ml]明显增高;AMI发病3h内血清HGF水平也比正常对照组增高[(893.2±61.6)pg/mlvs(619.5±31.1)pg/ml];A-MI组血清HGF浓度与入院时cTnI、CK-MB及CK-MB峰值均无相关性;ACS患者血清HGF浓度与入院时CRP呈显著相关性。结论ACS患者血清HGF浓度增高,且与疾病的严重性呈正比;HGF的产生可能与ACS的炎症反应有关;血清HGF有可能成为临床上诊断早期AMI的一个新指标。     

关于高血压患者血清HGF、sICAM-1水平的研究（英文）

目的：探讨高血压患者血清肝细胞生长因子（HGF）,可溶性细胞间黏附分子-1（sICAM-1）水平的变化及其意义。方法：选择59例高血压患者,其中高血压1级组20例,高血压2级组19例,高血压3级组20例,并选择30例健康体检者作为正常对照组。用酶联免疫双抗体夹心法检测各组血清HGF和sICAM-1浓度,并进行比较。结果：与正常对照组相比,高血压患者血清HGF[（641.65±142.90）pg/ml比（998.15±241.38）pg/ml]、sI-CAM-1[（161.70±32.36）ng/ml比（327.17±31.28）ng/ml]水平明显升高（P〈0.01）,血压越高,其变化越显著（P〈0.01）,HGF浓度与sICAM-1浓度呈正相关（r=0.317,P〈0.01）。结论：HGF与sICAM-1可能参与了高血压的发病过程,而且HGF在高血压内皮细胞损伤的修复中可能具有重要作用。     

结直肠癌患者血清中血管内皮生长因子的水平及其意义

目的:测定结直肠癌患者血清血管内皮生长因子(VEGF)的含量,分析其与临床病理指标间的关系。方法:采用ELISA法测定42例初治结直肠癌患者血清VEGF含量,正常对照30例。结果:结直肠癌患者血清VEGF浓度为274.21±218.38 pg/ml,明显高于正常对照组浓度(169.06±68.01 pg/ml,P<0.02),结肠癌患者血清VEGF浓度为346.52±168.57 pg/ml明显高于直肠癌患者(237.31±124.10 pg/ml,P<0.05)。Dukes B、C、D期组患者血清VEGF浓度与对照组相比均有明显差异(P<0.05),Dukes D期组与Dukes A、B、C期组亦均有明显差异(P<0.05)。结直肠癌患者血清VEGF浓度与年龄、性别无相关性(P>0.05)。结论:VEGF与结直肠癌的发生发展及癌肿部位有关,对探讨结直肠癌的发生机制,病情判断,预后及指导治疗有一定价值,对早期诊断似无帮助。     

原发性高血压赖诺普利治疗前后血清胰岛素样生长因子-Ⅰ的变化

目的观察原发性高血压(EH)患者服用赖诺普利治疗前后血清胰岛素样生长因子-Ⅰ(IGF-Ⅰ)的变化,探讨IGF-Ⅰ在EH的发生发展过程中所起的可能作用.方法47例EH患者均行超声心动图检查,用放免法测定赖诺普利治疗前、治疗后半年及23例正常对照者血清IGF-Ⅰ水平.结果EH患者血清IGF-Ⅰ水平明显高于对照组分别为(22.23±10.06)ng/ml对(15.91±7.59)ng/ml,P＜0.01.Ⅰ～Ⅲ级间比较也有显著性差异(F=3.53,P＜0.05),Ⅲ级(28.61±13.10)ng/ml高于Ⅱ级(22.64±9.94)ng/ml,Ⅱ级高于Ⅰ级(18.09±6.11)ng/ml.EH伴左心室肥厚(LVH)者高于无LVH者(25.95±11.20)ng/ml对(18.68±7.43)ng/ml,P＜0.05.IGF-Ⅰ与左心室重量指数中度相关(r=0.54).赖诺普利治疗6个月后,血清IGF-Ⅰ水平由(22.23±10.06)ng/ml降至(16.82±7.93)ng/ml,P＜0.05.结论EH LVH患者IGF-Ⅰ水平升高,赖诺普利治疗后IGF-Ⅰ水平下降,IGF-Ⅰ可能参与EH LVH的形成.     

原发性高血压患者肝细胞生长因子、血管紧张素Ⅱ、内皮素的变化及苯那普利的干预作用

目的:探讨原发性高血压(EH)患者血清肝细胞生长因子(HGF)及血管紧张素Ⅱ(AngⅡ)、内皮素(ET)的浓度与原发性高血压进展的关系及苯那普利对其生成的影响.方法:以20例健康人做对照(正常对照组),另选择1、2级原发性高血压患者40例(为1级原发性高血压组18例,2级原发性高血压组22例),分别采用酶联免疫吸附法和放射免疫法测定苯那普利治疗前及治疗6周后血清中HGF、AngⅡ和ET浓度.结果:1、2级原发性高血压组治疗前血清HGF、ET和AngⅡ水平明显高于正常对照组(P＜0.05～0.01);并与平均动脉压呈正相关(r分别为0.568、0.460、0.623);血清HGF与ET、AngⅡ亦有良好相关性(r分别为0.512、0.563).治疗后血压下降,同时血清HGF、ET和AngⅡ水平较治疗前明显下降(P＜0.05).结论:HGF、AngⅡ及ET水平与高血压有关.苯那普利在降压的同时能降低HGF及AngⅡ、ET水平.     

原发性高血压赖诺普利治疗前后血清胰岛素样生长因子-I的变化

目的观察原发性高血压(EH)患者服用赖诺普利治疗前后血清胰岛素样生长因子-I(IGF-I)的变化,探讨IGF-I在EH的发生发展过程中所起的可能作用。方法47例EH患者均行超声心动图检查,用放免法测定赖诺普利治疗前、治疗后半年及23例正常对照者血清IGF-I水平。结果EH患者血清IGF-I水平明显高于对照组分别为(22.23±10.06)ng/ml对(15.91±7.59)ng/ml,P<0.01。I~Ⅲ级间比较也有显著性差异(F=3.53,P<0.05),Ⅲ级(28.61±13.10)ng/ml高于Ⅱ级(22.64±9.94)ng/ml,Ⅱ级高于I级(18.09±6.11)ng/ml。EH伴左心室肥厚(LVH)者高于无LVH者(25.95±11.20)ng/ml对(18.68±7.43)ng/ml,P<0.05。IGF-I与左心室重量指数中度相关(r=0.54)。赖诺普利治疗6个月后,血清IGF-I水平由(22.23±10.06)ng/ml降至(16.82±7.93)ng/ml,P<0.05。结论EHLVH患者IGF-I水平升高,赖诺普利治疗后IGF-I水平下降,IGF-I可能参与EHLVH的形成。     

Hepatocyte growth factor (HGF) as a potential index of severity of hypertension.

Hepatocyte Growth Factor (HGF) is a mesenchyme-derived pleiotropic factor that regulates cell growth, cell motility, and morphogenesis of various cells, and is thus considered a humoral mediator of epithelial-mesenchymal interactions. We previously identified HGF as a novel member of the family of endothelium-specific growth factors. Moreover, the presence of a local HGF system (HGF and its specific receptor, c-met) has been demonstrated in vascular cells both in vitro and in vivo. HGF might contribute to the protection and/or repair of vascular endothelial cells injured by high blood pressure. If so, serum HGF level might be elevated in response to endothelial cell damage. To test this hypothesis, we measured serum levels of HGF in hypertensive and normotensive patients. Serum HGF concentration in hypertensive patients without any complications was significantly higher than that in normal subjects. Interestingly, serum HGF concentration in hypertensive patients with complications was significantly higher than that in either hypertensive patients without complications or normotensive subjects. Of importance, hypertensive patients treated with antihypertensive drugs showed the same level of serum HGF concentration as normotensive subjects. In contrast, serum HGF concentration in diabetic patients without hypertension was significantly lower than that in normal subjects, whereas serum HGF concentration in diabetic patients with hypertension was significantly higher than that in normal subjects. Moreover, serum HGF concentration in diabetic patients with hypertensive complications was even higher than that in diabetics without complications. This review discusses the possibility that HGF may be considered as a new index of the severity of hypertension.     

Hormone replacement therapy causes a decrease in hepatocyte growth factor in hypertensive women

OBJECTIVE: Serum hepatocyte growth factor (HGF) is associated with blood pressure. We investigated whether the serum HGF level differs between hypertensive and normotensive postmenopausal women (PMW) and whether hormone replacement therapy (HRT) alters the serum HGF level and blood pressure in hypertensive and normotensive PMW. DESIGN: Prospective observational study. METHODS: A total of 33 PMW with mild to moderate essential hypertension controlled by antihypertensive treatment (mean age, 57 +/- 6 years) and 23 normotensive PMW (mean age, 57 +/- 7 years) received continuous HRT (0.625 mg of conjugated equine estrogen combined with 2.5 mg of medroxyprogesterone acetate) once a day orally for 12 months, and we measured serum HGF levels and blood pressure before and 12 months after the start of HRT. RESULTS: The baseline serum HGF level was significantly higher in hypertensive PMW than in normotensive PMW. HRT significantly decreased the serum HGF level in hypertensive subjects, from 2.85 +/- 0.64 pmol/l to 2.49 +/- 0.65 pmol/l (P < 0.001), but not in normotensive subjects. HRT did not change blood pressure in either group. CONCLUSIONS: Serum HGF level before the start of HRT was higher in the hypertensive PMW than in the normotensive PMW. Furthermore, HRT decreases serum HGF without decreasing blood pressure in hypertensive PMW. The HRT-induced decrease in serum HGF was greater in hypertensive PMW than in normotensive PMW, and the decrease was independent of blood pressure changes.     

Hepatocyte growth factor and 24-hour ambulatory blood pressure monitoring.

In recent years, many growth factors and cytokines have been shown to be related to arteriosclerosis, and hepatocyte growth factor (HGF) has been reported to be associated with hypertension. In the present study, we investigated the relationship between HGF and hypertension by measuring the serum HGF concentration and performing 24-h ambulatory blood pressure monitoring (ABPM) in 47 randomly selected male and female subjects who underwent a medical examination for cardiovascular disease. The results were as follows. 1) The mean serum HGF concentration in the subjects was 0.35+/-0.14 ng/ml. 2) The serum HGF concentration was positively correlated with both the nighttime systolic and diastolic blood pressures (r=0.42, p<0.05 and r=0.47, p<0.01, respectively). 3) No correlation was found between serum HGF concentration and daytime systolic or diastolic blood pressure. 4) When subjects were divided into two groups based on the difference between daytime and nighttime systolic blood pressure, i.e., a group in which the difference was less than 10 mmHg and a group in which the difference was 10 mmHg or more, the HGF concentration was significantly higher in the former group (0.39+/-0.14 vs. 0.30+/-0.12 ng/ml, p<0.05); similarly, when subjects were divided into a group in which the difference between daytime and nighttime diastolic blood pressure was 5 mmHg and a group in which the difference was 5 mmHg or more, the HGF concentration was significantly higher in the former group (0.42+/-0.15 vs. 0.31+/-0.12 ng/ml, p<0.05). The results indicated that there is a relationship between blood pressure measured by ABPM and serum HGF concentration, and that this relationship might be an index of damage to blood vessels in patients with hypertension.     

肝细胞生长因子在内皮细胞和高血压中的研究进展

肝细胞生长因子(HGF)是一种内皮细胞特异性生长因子,促进内皮细胞的增殖和移行,抑制内皮细胞的凋亡。高血压患者血清HGF水平与血压高低、靶器官损害程度和血压节律异常有关,可能成为反映高血压内皮功能不全的一个新指标。一些药物能降低高血压患者血清HGF水平。     

Effect of nifedipine on endothelial function in normotensive smokers: potential contribution of increase in circulating hepatocyte growth factor

Calcium antagonists are reported to have protective effects on the endothelium in vitro and in vivo. Especially, nifedipine, among many calcium antagonists, was shown to improve endothelial dysfunction in patients with hypertension. However, no report has determined whether the improvement of endothelial dysfunction by nifedipine is due to direct effects or indirect effects such as its hypotensive effect. Thus, in this study, we evaluated the direct effects of nifedipine on smoking-induced endothelial dysfunction, since cigarette smoking itself is a major factor in damage of endothelial cells, as well as hypertension. We examined whether nifedipine improves endothelial function in 10 normotensive smokers without any risk factors for atherosclerosis. The subjects were treated with 20 mg nifedipine monotherapy (n = 10) or placebo (n = 10) for 4 weeks. Nifedipine did not affect blood pressure and heart rate of normotensive smokers. We measured forearm blood flow (FBF) by strain-gauge plethysmography after 2 and 4 weeks of treatment. Changes in vasodilator response to reactive hyperaemia were significantly improved in nifedipine-treated subjects (P < 0.05), while there was no significant change in FBP response in control subjects. Response to nitroglycerin was not changed in either group. Moreover, to evaluate the mechanisms of the direct effects of nifedipine on the endothelium, we focused on hepatocyte growth factor (HGF), which is a novel angiogenic growth factor with an antiapoptotic action on endothelial cells. Interestingly, serum HGF concentration in smokers treated with nifedipine was significantly elevated both at 2 and 4 weeks (P < 0.05). Overall, these results demonstrated direct effects of nifedipine in the improvement of endothelial dysfunction in normotensive smokers. The increase in serum HGF concentration by nifedipine might contribute to the improvement of endothelial dysfunction.     

老年高血压病患者血清肿瘤坏死因子-α、白介素-6和C-反应蛋白水平的变化研究

目的 探讨在老年高血压病患者中,血清肿瘤坏死因子-α(TNF-α)、C-反应蛋白(CRP)和白细胞介素-6( IL-6)水平变化及意义.方法 24例正常血压老年人和28例老年高血压病患者,常规测量血压,抽取空腹静脉血检测其空腹血糖、血脂、血清胰岛素、IL-6、CRP和TNF-α水平.结果 与正常老年人群相比,在老年高血压者中,血清总胆固醇、三酰甘油、IL-6[(15.56±5.36)vs(26.86±2.49)μg/ml,P＜0.05]、CRP[(1.58±1.14)vs(2.29±1.42)mg/ml,P＜0.05]和TNF-α[(34.58±14.54)vs(56.82±32.14)ng/ml,P＜0.05]水平均高于正常血压人群.在老年高血压病患者中,血清CRP和TNF-α水平均与收缩压呈正相关,与舒张压无相关性.结论 老年高血压病患者中血清IL-6、CRP和TNF-α水平均增高并与收缩压呈正相关,提示高血压病与炎症密切相关.     

Circulating adhesion molecules levels in type 2 diabetes mellitus and hypertension

BACKGROUND: Risk factors for atherosclerosis such as hypertension, type 2 diabetes, obesity and dyslipidemia affect endothelial function and stimulate adhesion molecules expression. The aim of the study was to examine endothelial activation in type 2 diabetes and hypertension as indicated by adhesion molecule levels and further to investigate whether the coexistence of the above conditions has a different effect. METHODS: Serum levels of soluble E-selectin, ICAM-1 and VCAM-1 were measured in 17 hypertensive type 2 diabetic patients (DM-HY), 32 normotensive type 2 diabetic patients (DM), 11 hypertensive nondiabetic patients (HY) and 15 healthy subjects. RESULTS: In diabetic patients (either DM-HY or DM), soluble E-selectin levels were significantly increased compared to healthy subjects (p<0.001). In HY patients, both sE-selectin (66.44+/-71.59 vs. 29.42+/-15.56 ng/ml, p=0.033) and sVCAM-1 (1529+/-433.33 vs. 1027+/-243.56 ng/ml, p=0.03) levels were found significantly higher compared to healthy subjects (p<0.05). The coexistence of diabetes and hypertension (DM-HY) did not have an additive effect on circulating adhesion molecules levels compared with the levels observed in either diabetes or hypertension. Systolic and diastolic blood pressure (BP) were independent factors correlated respectively with sE-selectin and sVCAM-1 levels (R=0.454, p=0.034 and R=0.578, p=0.005) in nondiabetic subjects (hypertensive and normotensive). CONCLUSIONS: Type 2 diabetes mellitus and hypertension induce endothelial activation as indicated by elevated levels of soluble adhesion molecules. This effect is not different when comorbidity is present.     

Serum hepatocyte growth factor predicts ventricular remodeling following myocardial infarction.

Hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) stimulate endothelial cell proliferation and induce angiogenesis, but the timing and significance of their release in patients with acute myocardial infarction (AMI) are unknown in relation to future left ventricular remodeling. Venous blood samples were obtained at admission and up to 3 weeks later in 40 patients with AMI and in 40 age- and sex-matched control subjects. Blood samples were also taken from the coronary sinus (CS) in 20 patients on day 7 following AMI. Left ventricular end-diastolic volume in the subacute (1 week) and chronic (3 months) phases was assessed by left ventriculography to identify the remodeling group (n=15), which was defined as an increase in left ventricular end-diastolic volume index > or =5 ml/m(2) relative to the baseline value. Serum HGF and VEGF concentrations were higher in newly admitted patients with AMI than in the controls (HGF, 0.33 +/-0.09 vs 0.24+/-0.08 ng/ml, p<0.01; VEGF, 92.2+/-43.1 vs 67.2+/-29.8 pg/ml, p<0.01), peaking on day 7 (HGF, 0.41+/-0.12; VEGF, 161.7+/-76.9), and gradually decreasing between days 14 and 21. The HGF concentration in the CS did not differ from the concentration in the periphery, but the VEGF concentration was significantly more abundant in the CS than in the peripheral sample on day 7 (p<0.05). The serum HGF concentration on day 7 was higher in the remodeling group than in the nonremodeling group (0.47 +/-0.13 vs 0.36+/-0.09 ng/ml, p<0.01), but there was no difference between the groups on admission, day 14 and day 21. The serum VEGF concentration did not differ between the remodeling and nonremodeling groups at any time. Thus, the serum HGF concentration on day 7 after AMI is mostly from noncardiac sources and predicts left ventricular remodeling.     

Increase in peripheral blood flow by intravenous administration of prostaglandin E1 in patients with peripheral arterial disease, accompanied by up-regulation of hepatocyte growth factor.

Since endothelial damage is a trigger for the progression of atherosclerosis, we evaluated the clinical utility of prostaglandin E1 (PGE1) in relation to peripheral blood flow and regulation of hepatocyte growth factor (HGF), an angiogenic growth factor, in patients with peripheral arterial disease (PAD). Fourteen male patients with PAD who showed the characteristic symptoms of arteriosclerosis obliterans (Fontaine I: n=2; Fontaine II: n=4; Fontaine III: n=2; Fontaine IV: n=6), confirmed by angiography, were enrolled in this study. Patients were administrated synthetic PGE1 at a dose of 120 microg per day for 14 consecutive days. Measurement of peripheral blood flow and serum HGF concentration was performed before PGE1 treatment and after 14 days of administration. Interestingly, intravenous administration of PGE1 for 2 weeks significantly increased the blood flow as assessed by a laser Doppler imager (p<0.01). In patients with Fontaine III and IV, serum HGF concentration was significantly higher than that in patients with Fontaine I or II and normal subjects. Of importance, administration of PGE1 further increased serum HGF concentration as compared to that before treatment (p<0.01). The increase in circulating HGF might work as a compensatory mechanism to decrease local HGF expression in patients with PAD, since HGF acts as an angiogenic growth factor with anti-apoptotic actions on endothelial cells. Moreover, to confirm the stimulatory effect of PGE1 on HGF in vessels, we employed an in vitro culture system. PGE1 increased HGF production and the growth of human cultured vascular endothelial cells. The stimulatory effect of PGE1 on HGF production might be due to an increase in cAMP, since forskolin and 8-bromo-cAMP induced HGF production. In conclusion, we demonstrated that administration of PGE1 stimulated peripheral blood flow, accompanied by an increase in systemic HGF concentration. Also, our in vitro data suggested that PGE1 augmented not only the systemic HGF level, but also local HGF production, probably through cAMP accumulation, resulting in improvement of endothelial function and blood flow.