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T Ogihara

Publications and source records attributed to T Ogihara.

At least 199 records · Page 11Linked to original sources
PubMed1999

A new Lp(a) assay that is unaffected by apo(a) size polymorphism.

We developed sandwich ELISA methods in which anti-apo(a) kringle 4 type 5 through protease (K4 x 5-Pro) domain monoclonal antibody (clone: 203E2) is employed in each instance as the capture antibody and one of the three species of monoclonal antibody [Mab] (clones: 108B8, 202A9, 2B3) is used as the labeled antibody. Using serum containing apo(a) with 34 repeats of kringle 4 as the calibrator, a commercial kit using anti-Lp(a) polyclonal antibody (Pab) or anti-apo(a) Mab overestimated the Lp(a) concentration in samples containing apo(a) with more than 34 repeats of kringle 4 and underestimated the Lp(a) concentration in samples containing apo(a) with fewer than 34 repeats of kringle 4. Moreover, it was demonstrated that the ratios of commercial kit values to anti-apo(a) K4 x 5-Pro Mab-based method values increased as the size of apo(a) increased. The ratios of apo(a) K5 x Pro Mab-based method values to anti-apo(a) K4 x 5-Pro Mab-based method values, however, remained almost constant regardless of the size polymorphism. Thus, we suggest that apo(a) size heterogeneity can significantly affect Lp(a) measurement in the Lp(a) assay using anti-Lp(a) Pab. The novel Lp(a) assay method, using only anti-apo(a) K4 x 5-Pro Mab, is not subject to this phenomenon.

Antibodies, Monoclonal↗
PubMed1999

Imidapril, an angiotensin-converting enzyme inhibitor, improves insulin sensitivity by enhancing signal transduction via insulin receptor substrate proteins and improving vascular resistance in the Zucker fatty rat.

Angiotensin-converting enzyme (ACE) inhibitors are antihypertensive agents, that inhibit the conversion of angiotensin I to angiotensin II, resulting in smooth-muscle relaxation and a reduction of vascular resistance. Recently, it has been suggested that ACE inhibitors improve insulin resistance in diabetic patients. To investigate the effect of an ACE inhibitor on insulin sensitivity, insulin signaling, and circulation, imidapril was administered orally or intraduodenally to Zucker fatty rats. Oral administration of imidapril improved insulin sensitivity based on the results of an oral glucose tolerance test (OGTT) and a decrease in urinary glucose secretion. Phosphatidylinositol 3-kinase (PI 3-kinase) activity associated with hepatic insulin receptor substrate-1 (IRS-1) in the insulin-stimulated condition was significantly enhanced 110% without a significant alteration in tyrosine phosphorylation of IRS-1 in the imidapril-treated group. In muscle, IRS-1 tyrosine phosphorylation and PI 3-kinase activity associated with IRS-1 in the insulin-stimulated condition were enhanced 70% and 20%, respectively, in the imidapril-treated group. In contrast, an alteration of the IRS-2 pathway was observed only in liver; a significant insulin-induced increase in the IRS-2-associated PI 3-kinase over the basal level was observed in the imidapril-treated group but not in the control. In addition, treatment with imidapril was shown to significantly reduce blood pressure and increase blood flow in the liver and muscle. These results suggest that the ACE inhibitor imidapril may improve insulin sensitivity not only by acting directly on the insulin signaling pathway but also by increasing blood flow in tissues via normalization of vascular resistance, a major cause of hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

An ACTH-producing pituitary carcinoma developing Cushing's disease.

An autopsy case of an ACTH-producing pituitary carcinoma in a 59-year-old man who developed Cushing's disease is reported. The surgically removed pituitary tumor was diagnosed as chromophobe adenoma, however, pulmonary metastases appeared 2 years after the operation. Autopsy revealed a residual pituitary tumor in the sella turcica with systemic metastases to the lungs, liver, pulmonary lymph nodes, hypothalamus, dura mater, and the subarachnoid space of the midbrain and spinal cord. Immunohistochemistry revealed ACTH positivity in the tumor cells. Further immunohistochemical study showed positive high expression of Ki-67 in the tumor removed at surgery as well as in the autopsied tumor. Ki-67 labeling index provided valuable information about the invasive and proliferative potential compared to noninvasive benign pituitary adenoma.

Adrenocorticotropic Hormone↗
PubMed1999

Reduction of risk of pneumonia associated with use of angiotensin I converting enzyme inhibitors in elderly inpatients.

Pneumonia is a major direct cause of death in the elderly. Although aspiration based on a reduced cough reflex is one of the causes of pneumonia in the elderly, there are few studies of angiotensin-I converting enzyme inhibitors (ACE inhibitors), which are antihypertensive drugs that induce cough, as a factor influencing the incidence of pneumonia in institutionalized elderly subjects. To assess the effect of ACE inhibitors and dihydropiridine calcium-channel blockers on the incidence of pneumonia, we conducted a hospital-based case-control study. Cases were 55 pneumonia patients aged > or = 65 years during a 1-year period. The controls were elderly subjects, frequency matched to the cases by age and gender (n = 220). Data were collected on known risk factors and on medication for hypertension, consisting of ACE inhibitors, calcium-channel blockers, and nonantihypertensive medication. The significance of differences in risk factors was analyzed using univariate and multivariate comparisons of cases and controls. After adjustment for potential confounding factors, the relative risk estimates for pneumonia were 0.38 (95% confidence interval [CI], 0.15-0.97) and 1.84 (95% CI, 0.89-3.78) for ACE inhibitors and calcium-channel blockers, respectively, relative to nonantihypertensive medication. The preventive effect of ACE inhibitors on pneumonia was apparent in long-acting ACE inhibitor users (0.24; 95% CI, 0.07-0.88). We conclude that ACE inhibitor use is an independent factor reducing risk of pneumonia among elderly inpatients.

Aged↗
PubMed1999

Structural characterization of substrates for the anion exchange transporter in Caco-2 cells.

The present study was conducted to characterize the structural specificity of an anion exchange transporter in intestinal epithelial cells. The transport of carboxylic acids with hydroxyl group(s) at the 2, 3, 4, and/or 5 positions with respect to carboxylate was examined by using Caco-2 cells in the presence of bicarbonate ions on the basolateral side to enhance the activity of the anion-exchange transporter. In the presence of the bicarbonate ion gradient, transport of L-lactic acid consisted of a saturable process and a nonsaturable process as judged from the Eadie-Hofstee plot. The transport of L-lactic acid at 1 microM was reduced by sodium azide, dinitrophenol, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). It was also reduced by 2-, 4-, and 5-hydroxycarboxylic acids such as hydroxyacetic acid, 4-hydroxybutyric acid, and 5-hydroxydecanoic acid, but not by 3-hydroxycarboxylic acids such as 3-hydroxypropionic acid and 3-hydroxybutyric acid. Transport of both 2- and 4-hydroxybutyric acids involved saturable and nonsaturable processes, whereas that of 3-hydroxybutyric acid was nonsaturable and was not inhibited by DIDS. These results indicate that 3-hydroxycarboxylic acids might not be substrates for this anion exchange transporter in intestinal epithelial cells, suggesting that the position of hydroxylation is significant for molecular recognition by the transporter.

Antiporters↗
PubMed1999

Intratumoral injection of oligonucleotides to the NF kappa B binding site inhibits cachexia in a mouse tumor model.

Cancer cachexia, characterized by anorexia, weight loss and progressive tissue wasting, has been postulated to be mediated by various cytokines. However, the precise mechanism of cachexia induction is not fully explained. We have developed synthetic double-stranded oligodeoxynucleotides (ODN) as 'decoy' cis-elements that block the binding of nuclear factors to promoter regions of targeted genes, resulting in the inhibition of gene transactivation in vivo as well as in vitro. This novel molecular strategy could be useful for treating a broad range of human diseases including cancer. In this study, we injected decoy ODN targeting the transcriptional factor, NF-kappa B (NF kappa B) binding cis-elements, which are essential for transactivation of gene expression of cytokines, directly into tumors of adenocarcinoma colon26 in mice, in order to examine whether or not cachexia is alleviated by inhibiting the action of cytokines. Tumor growth was not affected by transfection of NF kappa B decoy ODN as compared with scrambled decoy ODN. Nevertheless, transfection of NF kappa B decoy, but not scrambled decoy, ODN resulted in attenuation of the reductions in body weight, epididymal fat, gastrocnemius muscle mass and food intake, which were induced by the tumor presence. Interleukin 6 mRNA in the tumor was also markedly decreased by the transfection of NF kappa B decoy ODN. It is known that the transcriptional factor E2F plays a pivotal role in the coordinated transactivation of cell cycle regulatory genes. Therefore, we hypothesized that the introduction of synthetic double-stranded DNA with high affinity for E2F in vivo as 'decoy' cis-elements might inhibit the tumor growth of colon26, resulting in turn in inhibition of cachexia induction. However, injection of E2F decoy ODN failed to inhibit tumor growth and cachexia induction, as compared with mismatched decoy ODN. Overall, the present study demonstrated that cachexia induced by adenocarcinoma colon26 was inhibited by blocking of NF kappa B, using a novel molecular decoy strategy, without an effect on tumor growth, and also that tumor growth and cachexia induction in the colon26 model were not affected by E2F decoy ODN. These results suggest that cytokines regulated by NF kappa B may play a pivotal role in the induction of cachexia by colon26, providing a new therapeutic strategy for cancer cachexia.

Adenocarcinoma↗
PubMed1999

Clinical efficacy and tolerability of candesartan cilexetil. Candesartan Study Groups in Japan.

Clinical trials of candesartan cilexetil conducted in Japan are reviewed. Candesartan cilexetil inhibited the pressor response to intravenous angiotensin II in healthy volunteers, with peak effects observed at 4 or 8 h after oral dosing; suppressing effects persisted up to 24 h. In 14 multicentre studies with 928 hypertensive patients treated for 8 to 12 weeks, candesartan cilexetil had an efficacy rate (reduction of systolic/diastolic blood pressure > or = 20/10 mm Hg and/or mean blood pressure > or = 13 mm Hg) of 72% and 63%, and an adverse effect rate of 9.9% and 7.3%, in patients with mild-to-moderate essential hypertension and those with impaired renal function, respectively. When data for elderly patients were analysed, there was no difference in efficacy and tolerability compared to non-elderly patients. In a double-blind comparative study, candesartan cilexetil was superior to enalapril in hypertensive patients: efficacy rate, 74% vs 66% (NS); adverse symptom rate, 10.4% vs 27.3% (P < 0.01); incidence of cough, 1.5% vs 14.8% (P < 0.01). Treatment with 2-8 mg of candesartan cilexetil once daily for 8 to 12 weeks reduced the left ventricular mass index without deterioration of cardiac function. In conclusion, 4-12 mg of candesartan cilexetil once daily is effective and well tolerated in patients with essential hypertension, including elderly patients, those with severe hypertension, and hypertensive patients with renal insufficiency. Its improved tolerability profile over angiotensin-converting enzyme inhibitors, as well as its end-organ protective effects, suggest that candesartan cilexetil is useful as a first-line antihypertensive drug.

Administration, Oral↗
PubMed1999

Effect of propranolol on central neurotransmitter release in Wistar rats analysed by brain microdialysis.

1. The effect of propranolol on amino acid neurotransmitter release in the rostral ventrolateral medulla (RVLM) was examined in urethane-anaesthetized male Wistar rats. 2. Amino acids released in the RVLM in response to intravenous administration of propranolol (0.4 mg/kg per min; n = 6) or nitroglycerin (0.02 mg/kg per min; n = 5) were determined by the brain microdialysis method. 3. Amino acids in dialysates were analysed by high-performance liquid chromatography and were quantified by ultraviolet absorbance. 4. Administration of both intravenous propranolol and nitroglycerin significantly decreased arterial blood pressure. Heart rate was decreased only by propranolol. 5. The reduction in arterial blood pressure produced by intravenous propranolol was accompanied by a decrease in the release of the excitatory amino acid glutamate in the RVLM. 6. The reduction in arterial blood pressure following intravenous nitroglycerin was not accompanied by a release of glutamate. 7. There were no significant changes in the levels of other amino acids (glycine, taurine, GABA) following either propranolol or nitroglycerin. 8. The decrease in glutamate release in the RVLM may account, in part, for the central depressor mechanism of propranolol.

Adrenergic beta-Antagonists↗
PubMed1999

Association of plasma fibrinogen level and blood pressure with diabetic retinopathy, and renal complications associated with proliferative diabetic retinopathy, in Type 2 diabetes mellitus.

AIM: To clarify the association of several clinical parameters, including plasma fibrinogen level, with diabetic retinopathy in patients with Type 2 diabetes mellitus (DM). METHODS: A total of 294 Japanese patients with Type 2DM were studied; 53 patients with no diabetic retinopathy (NDR), 90 with background diabetic retinopathy (BDR), and 151 with proliferative diabetic retinopathy (PDR). Multiple logistic regression analysis was performed to assess variables independently associated with diabetic retinopathy in two settings: presence of retinopathy of any severity and presence of advanced retinopathy. RESULTS: The following parameters were identified as independent factors associated with the presence of diabetic retinopathy (NDR vs. BDR + PDR): type of therapy (P<0.0005), log-transformed plasma fibrinogen level (P < 0.05), mean blood pressure (P < 0.05), and duration of diabetes (P < 0.05). The independent variables associated with advanced retinopathy were type of therapy (P<0.00005), age (P<0.0005) and nephropathy (P<0.05). Body mass index, smoking and hypertensive status, HbA1c and total cholesterol levels were not independently associated. CONCLUSIONS: These data suggest that in patients with Type 2 DM, an increased blood viscosity due to high fibrinogen level as well as an elevated intravessel pressure play a role in the development of diabetic retinopathy, and that the progression to PDR is influenced or accompanied by the deterioration of renal status.

Aged↗
PubMed1999

Length rather than a specific allele of dinucleotide repeat in the 5' upstream region of the aldose reductase gene is associated with diabetic retinopathy.

AIMS: To assess the possible contribution of a genetic factor to diabetic retinopathy. METHODS: (CA)n repeat length was investigated in the 5' upstream region of the gene coding for aldose reductase (AR), which is a key enzyme of the polyol pathway and plays a role in hyperglycaemia-induced tissue damage, in Japanese patients with Type 2 DM. RESULTS: The dinucleotide repeat length was significantly associated with proliferative diabetic retinopathy (PDR) (P= 0.029, Mann-Whitney U-test); i.e. shorter alleles were more prevalent in the PDR group than in the control group. CONCLUSIONS: (CA)n repeat length, rather than a specific allele, in the 5' upstream region of the AR gene is associated with diabetic retinopathy. These data suggest that the AR locus plays a role in genetic susceptibility to diabetic retinopathy and that dinucleotide repeats in genomic DNA may be related to disease predisposition.

Aged↗
PubMed1999

Deletion polymorphism in the gene for angiotensin-converting enzyme is not a risk factor predisposing to abdominal aortic aneurysm.

OBJECTIVE: to establish whether deletion of the angiotensin-converting enzyme (ACE) gene is a risk factor predisposing to abdominal aortic aneurysm (AAA) or not. METHODS: the study included 125 patients with AAA and 153 controls randomly selected from 328 individuals. The control subjects were confirmed not to have an AAA, but matched with the AAA group for age, sex, hypertension, diabetes mellitus, and hyperlipidaemia. The presence of ACE polymorphism was detected by a polymerase chain reaction using DNA extracted from blood. RESULTS: the distribution of ACE genotypes and allele frequencies in the control and AAA groups was not significantly different. CONCLUSION: the deletion polymorphism in the ACE gene is not a risk factor for AAA.

Aged↗
PubMed1999

Upregulation of renin-angiotensin system during differentiation of monocytes to macrophages.

BACKGROUND: We have demonstrated that accumulated macrophages in human coronary arteries strongly express angiotensin converting enzyme in accordance with the development of atheromatous plaques. However, there are few reports on the regulation of the renin-angiotensin system in macrophages and in monocytes as their source. OBJECTIVE: To examine whether the renin-angiotensin system is upregulated during the differentiation of monocytes to macrophages, and whether it is further regulated by angiotensin II and cytokines. MATERIALS AND METHODS: We used a human leukemia cell line, THP-1, for monocytes. Differentiated THP-1, induced by adding phorbol 12-myristate 13-acetate for 24 h, were used as macrophages. Expression of messenger RNA of the renin-angiotensin system components was measured by quantitative reverse-transcriptase polymerase chain reaction. Angiotensin converting enzyme activity and subtype-specific angiotensin-binding sites of cultured cells, and angiotensin II production in the culture medium were measured. RESULTS: Macrophages expressed all components of the renin-angiotensin system except chymase. Cellular angiotensin converting enzyme activity and angiotensin II in the medium were increased 3.2- and 4.5-fold during differentiation, respectively. Expression of angiotensin II type 1 (AT1) and type 2 (AT2) receptors was increased 6.2-and 6.4-fold during differentiation, and was sustained for 7 days. Incubation with angiotensin II for 24 h caused downregulation of both AT1 and AT2 receptor messenger RNA, but the expression levels were still more than threefold higher compared with monocytes. The density of binding sites of AT1 and AT2 receptors in macrophages was 0.26 +/- 0.02 and 0.15 +/- 0.01 fmol/10(6) cells, respectively. CONCLUSION: The renin-angiotensin system is markedly activated during monocyte/macrophage differentiation, and may participate in the development of atherosclerosis.

Angiotensin II↗
PubMed1999

Relative localization of angiotensin-converting enzyme, chymase and angiotensin II in human coronary atherosclerotic lesions.

BACKGROUND: Studies using cell cultures and animal models have indicated an important role for angiotensin II in atherosclerosis. In humans, at least two major enzymes are involved in the conversion of angiotensin I to angiotensin II: so-called angiotensin-converting enzyme (ACE) and chymase. Enhanced activation of chymase in atherosclerotic tissue homogenates has been reported in animal models, but its contribution to the generation of angiotensin II has not been studied. OBJECTIVE: To clarify the localization of chymase and its pathophysiologic role in the formation of angiotensin II, using human coronary arteries. DESIGN AND METHODS: Twenty-four coronary artery segments obtained from 14 autopsied patients were characterized histologically into the following categories: normal coronary arteries with diffuse intimal thickening, hypercellular lesions, atheromatous plaques and fibrosclerotic plaques. We compared the cellular localization of chymase, ACE and angiotensin II expression using immunocytochemical techniques. RESULTS: Chymase was expressed only in the cytosole of mast cells in all segments. On the basis of the histologic study, the number of chymase-positive cells in the intima of atheromatous plaques was significantly higher than that in normal coronary arteries with diffuse intimal thickening. The expression of angiotensin II in the intima was enhanced in hypercellular lesions and atheromatous plaques. Localization of angiotensin II in the intima was associated with that of ACE. Immunodouble staining did not show colocalization of angiotensin II and chymase. CONCLUSIONS: These results suggest an important role for the production of angiotensin II by ACE in the progression of atherosclerosis in human coronary arteries. Enhanced expression of chymase appears not to be involved in angiotensin II production in the intima.

Adolescent↗
PubMed1999

How useful is the detection kit for antibody to Helicobacter pylori in urine (URINELISA) in clinical practice?

OBJECTIVE: Increased knowledge of the significance of Helicobacter pylori (H. pylori) infection in gastric disorders has accelerated the trend of screening patients with dyspepsia for its infection. Serological examination of antibody for H. pylori has been widely performed. Recently, a urine-based enzyme-linked immunosorbent assay (URINELISA) kit for detection of antibody for H. pylori has been developed. Accordingly, we evaluated its diagnostic accuracy in clinical practice. METHODS: Subjects of this study were 132 patients who presented at our university hospital because of dyspeptic symptoms (81 men, 51 women; age, 41.5+/-1.4 yr). 13C urea breath test, blood drawing for serological antibody for H. pylori infection by four different kits, and urine collection for the URINELISA test for detection of the antibody were performed. Diagnostic accuracy of the commercially available antibodies in serum and in urine were investigated using the results of the 13C urea breath test as the gold standard. RESULTS: Sensitivity, specificity, and accuracy of URINELISA were 86.3% (95% confidence intervals [CI], 76-93%), 91.5% (95% CI, 81-97%), and 88.6% (95% CI, 82-93%), respectively, which were comparable to those of imported serological kits. CONCLUSIONS: The URINELISA kit for detecting anti-H. pylori antibody in urine provides diagnostic accuracy comparable to that of imported kits for detecting antibodies in serum and is considered to be clinically useful for the diagnosis of H. pylori infection.

Adult↗
PubMed1999

Raised concentrations of aldehyde lipid peroxidation products in premature infants with chronic lung disease.

AIM: To indicate the extent of lipid peroxidation induced by oxidative stress, by measuring aldehyde end products in biological samples. METHODS: A highly specific gas chromatography and mass spectrometry (GC/MS) method was used to measure plasma concentrations of aliphatic aldehydes within the first week of life in 13 premature infants who subsequently developed chronic lung disease (CLD) and 11 infants without CLD (non-CLD). The oxime-tert-butyldimethylsilyl derivatives of aldehydes were analysed using 2,2,6,6-d4-cyclohexanone as the internal standard. RESULTS: All of the aldehydes measured were raised in those infants with CLD compared with non-CLD infants. Plasma concentrations of heptanal, 2-nonenal, and 4-hydroxynonenal (HNE) were significantly increased in CLD infants on the day of birth, while the differences in all aldehydes between the two groups were not significant at 4-6 days of age. Logistic regression analysis showed that the increase in these three aldehydes within the first 24 hours of life independently showed significant associations with the development of CLD. In particular, an HNE concentration of > or = 200 nM on day 0 was the best predictor for the early detection of CLD (odds ratio = 32.0), followed by a 2-nonenal concentration of > or = 150 nM (odds ratio = 16.0). CONCLUSIONS: These findings suggest that lipid peroxidation may have a role in the pathogenesis of neonatal CLD.

Aldehydes↗
PubMed1999

Angiotensin II type 1 receptor-mediated peroxide production in human macrophages.

Our previous experiments demonstrated upregulation of the renin-angiotensin system in macrophages, including angiotensin II type 1 (AT1) and type 2 (AT2) receptors, during transformation from monocytes. We investigated the role of angiotensin II in oxidative stress of monocytes/macrophages, which plays a role in the advance of atherosclerosis. THP1, a human monocytic leukemia cell line, was differentiated to macrophages by adding of phorbol 12-myristate 13-acetate for 24 hours. The intracellular production of peroxide was measured by a cytofluorometric assay with 2', 7'-dichlorofluorescein-diacetate with a flow cytometer scan. Peroxide was detected in monocytes and upregulated during the transformation to macrophages by 3.18+/-0.52 times in relative fluorescein of peak value (P<0.01). Angiotensin II (1 micromol/L) induced oxidative stress in macrophages, with the peak at 15 minutes by 451+/-223%, and returned to the control level within 1 hour. EC50 was 5.4x10(-9) mol/L. AT1 antagonist (CV11974, 1 micromol/L) significantly decreased angiotensin II-induced oxidative stress in macrophages, but AT2 antagonist (PD123319, 1 micromol/L) did not. Of interest, AT1 antagonist also decreased basal levels of peroxide production in macrophages in a dose-dependent manner. These results suggest that upregulation of the expression of AT1 receptor in macrophages contributes in part to upregulation of peroxide production. AT1 receptor antagonists may be useful to suppress oxidative stress of macrophages in atherosclerotic lesions.

Angiotensin II↗
PubMed1999

Therapeutic angiogenesis induced by human recombinant hepatocyte growth factor in rabbit hind limb ischemia model as cytokine supplement therapy.

Hepatocyte growth factor (HGF) exclusively stimulates the growth of endothelial cells without replication of vascular smooth muscle cells and acts as a survival factor against endothelial cell death. Therefore we hypothesized that a decrease in local vascular HGF might be related to the pathogenesis of peripheral arterial disease. We initially evaluated vascular HGF concentration in the vessels of patients with arteriosclerosis obliterans. Consistent with in vitro findings that hypoxia downregulated vascular HGF production, vascular HGF concentration in the diseased segments of vessels from patients with arteriosclerosis obliterans was significantly decreased as compared with disease-free segments from the same patients (P<0.05), accompanied by a marked reduction in HGF mRNA. On the other hand, a novel therapeutic strategy for ischemic diseases that uses angiogenic growth factors to expedite and/or augment collateral artery development has recently been proposed. Thus in view of the decreased endogenous vascular HGF, rhHGF (500 micrograms/animal) was intra-arterially administered through the internal iliac artery of rabbits in which the femoral artery was excised to induce unilateral hind limb ischemia, to evaluate the angiogenic activity of HGF, which could potentially have a beneficial effect in hypoxia. Administration of rhHGF twice on days 10 and 12 after surgery produced significant augmentation of collateral vessel development on day 30 in the ischemic model as assessed by angiography (P<0.01). Serial angiograms revealed progressive linear extension of collateral arteries from the origin stem artery to the distal point of the reconstituted parent vessel in HGF-treated animals. In addition, we examined the feasibility of intravenous administration of rhHGF in a moderate ischemia model. Importantly, intravenous administration of rhHGF also resulted in a significant increase in angiographic score as compared with vehicle (P<0.01). Overall, a decrease in vascular HGF might be related to the pathogenesis of peripheral arterial disease. In the presence of decreased endogenous HGF, administration of rhHGF induced therapeutic angiogenesis in the rabbit ischemic hind limb model, as potential cytokine supplement therapy for peripheral arterial disease.

Aged↗