Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Hepatocyte growth factor and 24-hour ambulatory blood pressure monitoring. 1245 15

Hepatocyte growth factor is a pleiotropic cytokine with cardioprotective properties. Its serum concentration is markedly raised in end-stage renal disease. This study assessed the relation of hepatocyte growth factor (HGF) with left ventricular mass and geometry in end-stage renal disease. Serum HGF measurements and echocardiographic studies were performed in 185 patients receiving hemodialysis. Patients with serum HGF above the median (1.85 ng/mL) had more frequent cardiovascular complications. This cytokine was directly related to mean left ventricular wall thickness (r=0.23, P=0.002) and relative wall thickness (r=0.25, P=0.0001); a multivariate analysis showed that this relation was independent of other risk factors. Accordingly, the prevalence of left ventricular concentric geometry (either concentric left ventricular hypertrophy or remodeling) was much higher (n=49, 53%) among patients with HGF values above the median that in those with values < or =1.85 ng/mL (n=31, 34%). Furthermore, the risk for left ventricular concentric geometry was higher in patients with HGF values above the median (odds ratio, 2.57; 95% CI, 1.33 to 4.98; P=0.005), and multiple logistic regression analysis confirmed that this association was independent of other risk factors. In patients receiving hemodialysis, elevated serum HGF is associated with concentric left ventricular geometry. This is consistent with reports that link this cytokine to arterial remodeling and survival in patients with end-stage renal disease and suggests that it is part of a counterregulatory response aimed at attenuating cardiovascular damage in this high-risk population.
Hypertension 2003 Jan
PMID:Hepatocyte growth factor and left ventricular geometry in end-stage renal disease. 1251 35

Risk factors for progression of kidney disease include hypertension, proteinuria, male sex, obesity, diabetes mellitus, hyperlipidemia, smoking, high-protein diets, phosphate retention, and metabolic acidosis. Angiotensin II production upregulates the expression of transforming growth factor-beta1, tumor necrosis factor-alpha, nuclear factor-kappaB, and several adhesion molecules and chemoattractants. In addition to angiotensin, other vasoactive compounds, such as thromboxane A(2), endothelin, and prostaglandins, are upregulated. Treatment with one of several growth factors may ameliorate the progression of kidney disease: insulin-like growth factor-1, hepatocyte growth factor, and bone morphogenetic protein-7.
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PMID:Progression of chronic renal disease. 1261 42

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.
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PMID:Effect of nifedipine on endothelial function in normotensive smokers: potential contribution of increase in circulating hepatocyte growth factor. 1507 89

Hepatocyte growth factor (HGF) is a growth factor which contributes to protection and/or repair of vascular endothelial cells. Serum HGF level is elevated in response to hypertensive organ damage, which suggests that blood pressure regulation may be affected by HGF gene polymorphisms via serum HGF. To examine the interaction between a HGF gene polymorphism and hypertension, we carried out a case-control study. The present study was conducted in outpatients of Osaka University Hospital. Subjects (n=654) who gave informed consent to the study protocol and genetic analysis were recruited. A C to A nucleotide substitution in intron 13 of the HGF gene was determined by the TaqMan polymerase chain reaction (PCR) method using an MGB (Minor Groove Binder) probe. The genotype distribution of the C/A polymorphism of the HGF gene in total subjects was as follows: CC, 83%; CA, 16%; and AA 1%. This distribution was not significantly different from the predicted by Hardy-Weinberg's equilibrium. The prevalence of hypertension was significantly higher in subjects with the CC genotype than in those with an A allele, and the positive association remained after adjustment for confounding factors, with the estimated odds ratio for hypertension (CC vs. CA+AA) being 1.71 (95% confidence interval: 1.02-2.93). A significant association with hypertension was observed in lean or female subjects but not in obese or male subjects. In conclusion, our data suggested that C/A polymorphism in intron 13 of the HGF gene is associated with susceptibility to essential hypertension in lean or female subjects.
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PMID:Association between hepatocyte growth factor gene polymorphism and essential hypertension. 1512 82

Therapeutic angiogenesis using angiogenic growth factors is expected to be a new treatment for patients with critical limb ischemia (CLI). Because hepatocyte growth factor (HGF) has potent angiogenic activity, we investigated the safety and efficiency of HGF plasmid DNA in patients with CLI as a prospective open-labeled clinical trial. Intramuscular injection of naked HGF plasmid DNA was performed in ischemic limbs of 6 CLI patients with arteriosclerosis obliterans (n=3) or Buerger disease (n=3) graded as Fontaine III or IV. The primary end points were safety and improvement of ischemic symptoms at 12 weeks after transfection. Severe complications and adverse effects caused by gene transfer were not detected in any patients. Of particular importance, no apparent edema was observed in any patient throughout the trial. In addition, serum HGF concentration was not changed throughout the therapy period in all patients. In contrast, a reduction of pain scale of more than 1 cm in visual analog pain scale was observed in 5 of 6 patients. Increase in ankle pressure index more than 0.1 was observed in 5 of 5 patients. The long diameter of 8 of 11 ischemic ulcers in 4 patients was reduced >25%. Intramuscular injection of naked HGF plasmid is safe, feasible, and can achieve successful improvement of ischemic limbs. Although the present data are conducted to demonstrate the safety as phase I/early phase IIa, the initial clinical outcome with HGF gene transfer seems to indicate usefulness as sole therapy for CLI.
Hypertension 2004 Aug
PMID:Safety evaluation of clinical gene therapy using hepatocyte growth factor to treat peripheral arterial disease. 1523 69

Hepatocyte growth factor (HGF) is a potent angiogenic and antifibrotic factor. Cardioprotective effects of HGF for idiopathic dilated cardiomyopathy were examined in hamsters with electroporation of plasmid DNA into skeletal muscle. We used hamster skeletal muscle as a protein producer of HGF gene. A plasmid vector encoding HGF (HGF group, n=12) or empty plasmid (placebo group, n=12) was transferred with in vivo electroporation into tibialis anterior muscles of hamsters with inherited dilated cardiomyopathy (TO-2 strain). The HGF group had greater serum HGF levels (21.6+/-2.2 versus 0.11+/-0.07 ng/mL, P<0.05), higher left ventricular ejection fraction (47.9+/-9.4% versus 28.8+/-11.2%, P<0.05), and greater wall thickening (31.6+/-6.3% versus 19.7+/-6.1%, P<0.05) when compared with the placebo group. The HGF group had smaller areas of ventricular fibrosis (11.8+/-3.4% versus 17.1+/-3.5%, P<0.05) and lower hydroxyproline content (3.7+/-0.7 versus 5.1+/-0.9 micromol/g, P<0.05) than did the placebo group. The HGF group also had higher capillary density (1885+/-232 versus 1447+/-182 vessel/mm(2), P<0.05) and higher matrix metalloprotease-1 activity (13.1+/-3.5 versus 8.1+/-3.6 microg/collagen degraded per hour per gram tissue, P<0.05) than did the placebo group. Exogenous HGF might improve the deleterious changes in myocardial function and structure in the hamster with dilated cardiomyopathy. Systemic delivery of gene products with in vivo electroporation into skeletal muscle seemed to be an alternative means of direct gene delivery.
Hypertension 2004 Sep
PMID:Treatment of dilated cardiomyopathy with electroporation of hepatocyte growth factor gene into skeletal muscle. 1528 69

The pathophysiological role of endothelial cells is important in the mechanism of progression of atherosclerosis and improvement of endothelial function may be important for cardiovascular morbidity. Calcium antagonists are reported to have protective effects on the endothelium in vitro and in vivo. In this clinical study, we investigated the effect of calcium antagonist, benidipine, on endothelial function in the patients with essential hypertension, which causes endothelial dysfunction. Twenty-five patients with hypertension without other risk factors for atherosclerosis were treated with monotherapy (8 mg benidipine, n=25) for 8 weeks. Blood pressure was reduced significantly. Endothelial function was evaluated using forearm blood flow by strain-gauge plethysmography after 8 weeks of treatment. Changes in vasodilator response to reactive hyperemia were significantly improved (p<0.01), while the response to nitroglycerin was not changed, suggesting the improvement of endothelial function. Moreover, we focused on hepatocyte growth factor (HGF), which is a novel angiogenic growth factor with an anti-apoptotic action on endothelial cells, and evaluated involvement of HGF in improvement of endothelial function. Serum HGF concentration in subjects treated with benidipine was significantly elevated at 8 weeks (p<0.05). Overall, these results demonstrated that benidipine improved endothelial dysfunction in patients with hypertension. Interestingly, an increase in serum HGF concentration by benidipine might contribute to the improvement of endothelial dysfunction.
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PMID:A calcium-channel blocker, benidipine, improves forearm reactive hyperemia in patients with essential hypertension. 1606 Apr 15

There is no specific treatment to improve the functional recovery in the chronic stage of ischemic stroke. To provide the new therapeutic options, we examined the effect of overexpression of hepatocyte growth factor (HGF) in the chronic stage of cerebral infarction by transferring the HGF gene into the brain using hemagglutinating virus of Japan envelope vector. Sixty rats were exposed to permanent middle cerebral artery occlusion (day 1). Based on the sensorimotor deficits at day 7, the rats were divided equally into control vector or HGF-treated rats. At day 56, rats transfected with the HGF gene showed a significant recovery of learning and memory in Morris water maze tests (control vector 50+/-4 s; HGF 33+/-5 s; P<0.05) and passive avoidance task (control vector 132.4+/-37.5 s; HGF 214.8+/-26.5 s; P<0.05). Although the total volume of cerebral infarction was not related to the outcome, immunohistochemical analysis for Cdc42 and synaptophysin in the peri-infarct region revealed that HGF enhanced the neurite extension and increased synapses. Immunohistochemistry for glial fibriary acidic protein revealed that the formation of glial scar was also prevented by HGF gene treatment. Additionally, the number of the arteries was increased in the HGF group at day 56. These data demonstrated that HGF has a pivotal role for the functional recovery after cerebral infarction through neuritogenesis, improved microcirculation, and the prevention of gliosis. Our results also provide evidence for the feasibility of gene therapy in the chronic stage of cerebral infarction.
Hypertension 2006 Apr
PMID:Gene transfer of hepatocyte growth factor gene improves learning and memory in the chronic stage of cerebral infarction. 1650 98

Embryonic stem (ES) cells are highlighted as promising cell sources for regenerative medicine. Here, we focused on providing the platform that forced ES cells to reproduce the vascular organization process, leading to efficiency and safety evaluation as preclinical testing of biological agents. Murine ES cell-derived embryoid bodies on matrigel, but not collagen or gelatin, could be differentiated into sprouting blood vessels without the addition of growth factors. The expression of endothelial cell marker CD31 and smooth muscle marker alpha-smooth muscle actin was partially colocalized and started to increase 7 days after culture on matrigel, accompanied by the induction of a number of growth factors, such as vascular endothelial growth factor, fibroblast growth factor-2, hepatocyte growth factor, transforming growth factor-beta, and angiopoietin-1. Moreover, notch-related genes, such as Del1 or Del4 (delta-like 1/4) and hey1 or hey2 (hairy/enhancer of split related TRPW motif 1/2), were upregulated in a similar time course. The treatment of neutralizing antibodies against these growth factors failed to inhibit the differentiation into the sprouting blood vessels, whereas arginine-glycine-aspartic peptide, a selective inhibitor for the alphavbeta3-integrins, did inhibit differentiation. An anticancer drug to inhibit angiogenesis, TNP-470, also blocked the vascular formation in this model. ES cells could reproduce the vascular organization process on the biosynthetic scaffolds, such as matrigel, without the addition of growth factors. In the future, a human ES-based tissue model would be an optional tool for the screening of pharmaceutical drugs for vascular disease.
Hypertension 2006 Jul
PMID:Model of vasculogenesis from embryonic stem cells for vascular research and regenerative medicine. 1675 88


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