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。     

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0.321±0.125 ng/ml; 原发性高血压组为0.368±0.269 ng/ml,二组之间无显著性差异(P>0.05).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.     

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。     

高血压患者血肝细胞生长因子与血管内皮功能的关系及干预研究

目的研究高血压患者血清肝细胞生长因子(HGF)与血管内皮功能不全的相关性;氯沙坦/氢氯噻嗪复方片(海捷亚)是否可降低高血压患者血清HGF水平和改善血管内皮功能。方法高血压(HT)患者70例,包括1级高血压(HT1组)患者27例、2级高血压(HT2组)患者31例、3级高血压(HT3组)患者12例。选择其中30例HT患者行海捷亚干预治疗。20例健康体检者为正常对照组。分别测定基线及海捷亚治疗后血清HGF、血浆内皮素(ET)和血清一氧化氮(NO)水平。结果1)血HGF和ET水平:HT3组高于HT2组、HT1组和对照组(P均<0.05),HT2组和HT1组高于对照组(P均<0.05),HT2组和HT1组之间无显著性差异(P值分别为0.061和0.162);血清NO水平:HT各组均低于对照组,且随着血压级别的增高而降低(P均<0.05);2)相关分析结果显示:血清HGF与NO呈负相关、与ET呈正相关(相关系数分别为-0.633、0.741,P值均<0.01);3)海捷亚治疗8周后血清HGF和ET明显降低,而血清NO明显增高(P值均<0.01)。结论1)高血压患者血清HGF增高,其水平可能反映了血管内皮功能不全的严重程度;2)高血压患者应用海捷亚治疗后血清HGF水平下降、血管内皮功能改善。     

高血压患者血清肝细胞生长因子的表达及与血管内皮功能的关系

目的探讨高血压患者血清肝细胞生长因子(HGF)的表达及与血管内皮功能的关系。方法 60例高血压患者,按血压高低分级分为轻度组(n=21)、中度组(n=27)及重度组(n=12),另选取30例健康体检者作为对照组,比较各组受试者基线指标及HGF、血浆内皮素(ET)及血浆一氧化氮(NO)水平,同时分析HGF水平与ET及NO的相关性。结果各组受试者性别、年龄、空腹血糖(FBG)、甘油三酯(TG)比较差异无统计学意义(P>0.05)。各组高血压患者血清HGF、ET及NO水平与对照组差异显著(P<0.05);HGF及ET水平随血压的增高而增高,NO水平随血压的增高而下降,重度组各指标与轻度组及中度组差异显著(P<0.05);轻度组与中度组HGF及NO水平差异显著(P<0.05)。Spearman相关性分析显示,HGF与ET水平呈显著正相关(r=0.69,P<0.05),HGF与NO水平呈显著负相关(r=-0.60,P<0.05)。结论高血压患者血液中HGF的水平与血压水平及机体血管内皮功能受损程度具有显著相关性,可作为反映高血压患者内皮功能受损程度的一个新指标。     

高血压患者血肝细胞生长因子与血管内皮功能的关系及干预研究

目的 研究高血压患者血清肝细胞生长因子(HGF)与血管内皮功能不全的相关性;氯沙坦/氢氯噻嗪复方片(海捷亚)是否可降低高血压患者血清HGF水平和改善血管内皮功能.方法 高血压(HT)患者70例,包括1级高血压(HT1组)患者27例、2级高血压(HT2组)患者31例、3级高血压(HT3组)患者12例.选择其中30例HT患者行海捷亚干预治疗.20例健康体检者为正常对照组.分别测定基线及海捷亚治疗后血清HGF、血浆内皮素(ET)和血清一氧化氮(NO)水平.结果 1) 血HGF和ET水平:HT3组高于HT2组、HT1组和对照组(P均＜0.05),HT2组和HT1组高于对照组(P均＜0.05),HT2组和HT1组之间无显著性差异(P值分别为0.061和0.162);血清NO水平:HT各组均低于对照组,且随着血压级别的增高而降低(P均＜0.05);2)相关分析结果显示:血清HGF与NO呈负相关、与ET呈正相关(相关系数分别为-0.633、0.741,P值均＜0.01);3)海捷亚治疗8周后血清HGF和ET明显降低,而血清NO明显增高(P值均＜0.01).结论 1)高血压患者血清HGF增高,其水平可能反映了血管内皮功能不全的严重程度;2)高血压患者应用海捷亚治疗后血清HGF水平下降、血管内皮功能改善.     

替米沙坦联合养血清脑颗粒对老年原发性高血压患者的影响

目的探讨替米沙坦联合养血清脑颗粒对老年原发性高血压(EH)患者的影响。方法选取2013年1月—2016年11月苏州市吴江区第一人民医院收治的老年EH患者120例,随机分为对照组和观察组,每组60例。对照组患者予以常规治疗,观察组患者在对照组基础上予以替米沙坦联合养血清脑颗粒治疗;两组患者均持续治疗2个月。比较两组患者临床疗效,治疗前后血压,血清肝细胞生长因子(HGF)、血管内皮生长因子(VEGF)水平及生活质量。结果观察组患者临床疗效优于对照组(P<0.05)。治疗前两组收缩压(SBP),舒张压(DBP),血清HGF、VEGF水平,精神状态评分,情感职能评分,社会功能评分,健康状况评分比较,差异无统计学意义(P>0.05);治疗后观察组患者SBP,DBP,血清HGF、VEGF水平低于对照组,精神状态评分、情感职能评分、社会功能评分、健康状况评分高于对照组(P<0.05)。结论替米沙坦联合养血清脑颗粒治疗老年EH的临床疗效确切,可有效降低患者血压及血清HGF、VEGF水平,提高患者生活质量。     

高血压患者血清肝细胞生长因子水平与血管内皮功能的关系及坎地沙坦酯的干预效果

目的探讨高血压患者血清肝细胞生长因子(HGF)水平与血管内皮功能的关系及坎地沙坦酯的干预效果。方法选择该院心血管内科2013年10月至2014年12月收治的高血压患者60例为病例组,同时选取30例健康体检者(血压正常)为对照组,检测血清HGF、内皮素(ET)、一氧化氮(NO)指标,分析血清HGF水平与血管内皮功能的关系及坎地沙坦酯的干预效果。结果病例组中随着病情加重HGF、ET-1水平逐渐升高,NO水平逐渐降低(P0.05);病例组各级别中NO、ET-1、HGF水平与对照组相比差异显著(P0.05)。病例组干预前经过检测HGF、NO、ET-1水平分别为(1 543.23±24.67)pg/ml、(12.38±2.36)μmol/L、(89.90±14.38)ng/L;HGF水平与NO呈负相关(r=-0.456,P=0.005),与ET-1呈正相关(r=0.765,P=0.001)。干预12 w后HGF与ET-1水平明显降低,NO水平明显升高,与干预前相比均具有统计学差异(P0.05)。结论高血压患者血清HGF明显升高,HGF水平变化与血管内皮功能密切相关,坎地沙坦酯干预后HGF水平下降,改善了血管内皮功能。     

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.     

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.     

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.     

Hepatocyte growth factor as cardiovascular hormone: role of HGF in the pathogenesis of cardiovascular disease

Hepatocyte growth factor (HGF) is a mesenchyme-derived pleiotropic factor which regulates cell growth, cell motility, and morphogenesis of various types of cells, and is thus considered a humoral mediator of epithelial-mesenchymal interactions responsible for morphogenic tissue interactions during embryonic development and organogenesis. Although HGF was originally identified as a potent mitogen for hepatocytes, HGF has also been identified as a member of angiogenic growth factors. Interestingly, the presence of its specific receptor, c-met, is observed in vascular cells, endothelial cells and cardiac myocytes. In addition, the mitogenic action of HGF on human endothelial cells was most potent among growth factors. Recent studies have demonstrated the potential application of HGF to treat cardiovascular disease such as peripheral vascular disease, myocardial infarction and restenosis after angioplasty. On the other hand, serum HGF concentration was significantly correlated with blood pressure. These results suggest that HGF secretion might be elevated in response to high blood pressure as a counter-system against endothelial dysfunction, and may be considered as an index of severity of hypertension. In this review, we discussed the potential role of HGF in cardiovascular disease.     

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.     

Serum hepatocyte growth factor concentration is correlated with the forearm vasodilator response in hypertensive patients

To evaluate the clinical importance of serum hepatocyte growth factor (HGF) concentration, we designed two clinical investigations. The first study analyzed the correlation between serum HGF concentration and clinical arterial stiffness or the vasodilator response to reactive hyperemia in hypertensive patients. The second study investigated the correlation between changes in serum HGF concentration and clinical arterial stiffness or reactive hyperemia during treatment with cilazapril or atenolol. A total of 210 hypertensive patients were analyzed in the first study, and 25 patients with essential hypertension were evaluated in the second study. Pulse wave velocity (PWV), strain gauge plethysmography, and serum HGF concentration were measured in the first study. We also evaluated these factors before and after treatment with either cilazapril (2.0 mg/day) or atenolol (25 mg/day) for 6 months in the second study. Serum HGF concentration was negatively correlated to reactive hyperemia in overall (r = 0.434, P < .0001) and nontreatment (r = 0.452, P < .0001) hypertensive patients. Arterial stiffness was weakly related to serum HGF concentration (P < .05) after adjusting for age and mean blood pressure (BP). By multiple regression analysis, only serum HGF concentration showed a strong independent correlation with reactive hyperemia, age and mean BP with PWV. Moreover, a relationship between endothelium-dependent vasodilation and serum HGF concentration was observed during treatment with cilazapril or atenolol (r = 0.406, P < .005). These results suggest that in evaluation of serum HGF concentration, the forearm vasodilator response to reactive hyperemia and PWV might be useful for managing hypertension in patients who are receiving antihypertensive therapy.     

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.     

Peritoneal fluid contains high concentration of hepatocyte growth factor and vascular endothelial growth factor after resection for hepatocellular carcinoma

BACKGROUND/AIMS: Surges in blood growth factor levels is a typical response to surgical stress. However, growth factor profiles in peritoneal fluid after hepatectomy for hepatocellular carcinoma (HCC) have not been clarified. We evaluated hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) in blood and peritoneal fluid preoperatively and postoperatively. METHODOLOGY: Serial blood and peritoneal fluid samples were collected from 47 patients who underwent curative hepatectomy for primary HCC at a university hospital. Blood samples were collected postoperative days 0, 1, 3, 5, and 7; peritoneal fluid was collected at the same time except day 0. VEGF and HGF concentrations were determined, and correlations between concentrations and clinical parameters of HCC were analyzed. RESULTS: HGF surges appeared postoperatively in blood and peritoneal fluid; concentrations paralleled each other. There was no postoperative surge of VEGF in blood, but peritoneal fluid VEGF concentration was remarkably high after hepatectomy. Both HGF and VEGF levels in blood and peritoneal fluid correlated with some clinical parameters. The difference in HGF and VEGF patterns in blood and peritoneal fluid imply that the origins of these two growth factors differ. CONCLUSIONS: Post-hepatectomy, VEGF and HGF levels surged in peritoneal fluid, whereas only HGF surged in blood, suggesting independent origins for the two growth factors. Both VEGF and HGF concentrations correlated with some clinical parameters.     

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.     

Identification of 21 single nucleotide polymorphisms in human hepatocyte growth factor gene and association with blood pressure and carotid atherosclerosis in the Japanese population

It has been suggested that circulating concentrations of hepatocyte growth factor (HGF) are increased in individuals with vascular endothelial damage, such as in hypertensive patients and subjects with atherosclerosis. Because the influence of genetic variation of HGF has not been examined, we identified single nucleotide polymorphisms (SNPs) in the HGF gene, and investigated the association between these SNPs and blood pressure or carotid atherosclerosis in the Japanese general population. We identified 21 SNPs in the HGF gene by direct sequencing in a test population of 32 Japanese subjects. Among them, considering allele frequency and linkage disequilibrium, three SNPs, C-1652T in the promoter, T43839A in intron 8, and T44222C in intron 9, were genotyped in 2412 members of the Japanese general population randomly selected from the residents in Suita city. None of the three SNPs were significantly associated with blood pressure. After adjusting for age, smoking habits, consumption of alcohol, and the presence of diabetes mellitus and dyslipidemia, female subjects with the T allele of T43839A had more severe carotid atherosclerosis compared to individuals with the A allele. This study provides the first evidence that HGF may be a candidate susceptibility loci that affects the progression of atherosclerosis in Japanese subjects.