Biomedical subjects

Hideo Kimura

Publications and source records attributed to Hideo Kimura.

At least 19 recordsLinked to original sources

PubMed2007

Differentiated astrocytes acquire sensitivity to hydrogen sulfide that is diminished by the transformation into reactive astrocytes.

Hydrogen sulfide (H2S) enhances the induction of hippocampal long-term potentiation (LTP) and induces calcium waves in astrocytes. Based on these observations, H2S has been proposed to be a synaptic modulator in the brain. Here we show that differentiated astrocytes acquire sensitivity to H2S that is diminished by their transformation into reactive astrocytes. Although sodium hydrosulfide hydrate (NaHS), a donor of H2S, did not increase the intracellular concentration of Ca2+ in progenitors, exposure of progenitors to leukemia inhibitory factor (LIF), which induces differentiation into glial fibrillary acidic protein (GFAP)-positive astrocytes, greatly increased the sensitivity to NaHS. In contrast, epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), dibutyryl cyclic AMP (db cAMP) and interleukin-1beta (IL-1beta) induced the conversion to reactive astrocytes with diminished sensitivity to NaHS. This suppressive effect of EGF on the sensitivity to NaHS was inhibited by cycloheximide, indicating that de novo protein synthesis was required for the suppression of H2S sensitivity.

Animals↗

PubMed2006

Spontaneous transformation of cultured mouse bone marrow-derived stromal cells.

Bone marrow-derived stromal cells have engendered interest because of their therapeutic potential for promoting tissue vascularization and repair. When mononuclear cells isolated from mouse bone marrow were cultured in DMEM supplemented with 10% fetal bovine serum, cell populations arose that showed rapid proliferation and loss of contact inhibition. These cells formed invasive soft tissue sarcomas after i.m. injection into nude or scid mice. I.v. injection resulted in the formation of tumor foci in the lungs. The tumors were transplantable into syngeneic immunocompetent mice. Direct injection of cultured cells into immunocompetent mice also resulted in tumor formation. Karyotype analysis showed that increased chromosome number and multiple Robertsonian translocations occurred at passage 3 coincident with the loss of contact inhibition. The remarkably rapid malignant transformation of cultured mouse bone marrow cells may have important implications for ongoing clinical trials of cell therapy and for models of oncogenesis.

Animals↗

PubMed2006

Hydrogen sulfide is a novel prosecretory neuromodulator in the Guinea-pig and human colon.

BACKGROUND & AIMS: Hydrogen sulfide (H(2)S) has been suggested as a novel gasomediator. We explored its unknown neuromodulatory role in human and guinea-pig colon. METHODS: We used immunohistochemistry to detect H(2)S-producing enzymes cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS) in enteric neurons, Ussing chambers to measure mucosal ion secretion, and neuroimaging with voltage- and Ca(++)-sensitive dyes to record H(2)S effects on guinea-pig and human enteric neurons. RESULTS: More than 90% of guinea-pig and human submucous and myenteric neurons were colabeled for CSE and CBS. Myenteric interstitial cells of Cajal were CSE-immunoreactive. The exogenous H(2)S donor NaHS (0.2-2.5 mmol/L) concentration-dependently increased chloride secretion in human and guinea-pig submucosa/mucosa preparations, but not in the colonic epithelial cell line T84. The secretory response was reduced significantly by tetrodotoxin (0.5 micromol/L), capsaicin desensitization (10 micromol/L), and the transient receptor potentials vanilloid receptor 1 antagonist capsazepine (10 micromol/L). The endogenous H(2)S donor L-cysteine also induced secretion that was diminished significantly by capsaicin desensitization, the CBS inhibitor amino-oxyacetic acid, and the CSE inhibitor propargylglycine. NaHS increased spike discharge in 23% of guinea-pig and 36% of human submucous neurons, but had no effect on Ca(++) mobilization in cultured guinea-pig enteric neurons. This excitatory response was reduced significantly by capsaicin desensitization and capsazepine, but not by glibenclamide (10 micromol/L). CONCLUSIONS: The presence of H(2)S-producing enzymes in human and guinea-pig enteric neurons, the excitatory action on enteric neurons, and the prosecretory effects of NaHS suggest H(2)S as a novel gut-signaling molecule. Its action mainly involves transient receptor potentials vanilloid receptor 1 receptors on extrinsic afferent terminals, which in turn activate enteric neurons.

Adult↗

PubMed2006

Autotaxin expression is enhanced in frontal cortex of Alzheimer-type dementia patients.

We searched for genes differentially expressed in the frontal cortices of Alzheimer-type dementia (ATD) patients compared with those of non-ATD controls using DNA microarray and quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses. Here we show that the expression level of the autotaxin (also called lysophospholipase D or ecto-nucleotide pyrophosphatase/phosphodiesterase 2) gene was significantly greater in ATD cortices than in non-ATD cortices. In both ATD and non-ATD groups, the expression levels were greater in patients with the apoE epsilon3/epsilon4 genotype than in patients with the apoE epsilon3/epsilon3 genotype, although the differences were not statistically significant. These observations suggest that expression of the autotaxin gene and cell signaling by lysophosphatidic acid may be involved in the pathology of ATD, and that this cell signaling pathway may be a potential target of treatments for ATD.

Aged↗

PubMed2006

Spontaneous mesenteric hemorrhage associated with Ehlers-Danlos syndrome.

The vascular type of Ehlers-Danlos syndrome is a genetic disorder of connective tissue and is frequently associated with catastrophic arterial complications. Its surgical treatment is extremely difficult because of the fragility of vessels. This article describes three patients with vascular type of Ehlers-Danlos syndrome who developed mesenteric hemorrhage due to spontaneous arterial rupture. The clinical and molecular characteristics of the disease are briefly reviewed.

Abdominal Cavity↗

PubMed2006

Clinical outcome and complications of temporary inferior vena cava filter placement.

OBJECTIVE: We evaluated the current clinical experience of temporary inferior vena cava (IVC) filter placement and its related complications. METHODS: From January 2000 to December 2005, we enrolled 33 patients (8 men and 25 women) who underwent percutaneous insertion of a temporary IVC filter in the Department of Vascular Surgery of Tokyo University Hospital. Deep vein thrombosis (DVT) was proven in 78.8% of the patients. The indications for filter insertion were contraindication to anticoagulation therapy (9.1%), thrombolytic therapy (12.1%), perioperative prophylactic implantation (84.8%), pregnancy with DVT (3.0%), and prophylactic implantation in the absence of DVT (15.2%). A Neuhaus Protect was used in 13 patients, and an Antheor was used in 20 patients. RESULTS: The mean +/- SD duration of filter placement was 10.6 +/- 7.0 days. There was no case of pulmonary embolism during filter protection and retraction. Filter thrombosis (capture of thrombus) was observed in four patients (12.1%), who then received additional thrombolytic therapy. Thrombi were dissolved by thrombolysis in three, one of whom had replacement with a permanent filter. The thrombus was not dissolved in one patient and was removed under venotomy at the insertion site. Major filter-related complications occurred in nine patients (27.3%), including filter dislocation in four patients (12.1%), catheter fracture in three (9.1%), and catheter-related infection in one (3.0%). In a patient with giant ovarian cancer, the IVC was nearly occluded with massive thrombus around the filter 2 days after operation, and the vena cava was then ligated under open laparotomy. No patients died during filter protection and retraction. CONCLUSIONS: Temporary IVC filters were effective for the prevention of fatal pulmonary embolism. However, our experience of a high incidence of complications related to temporary filters suggests that this device has limited indications and supports the need for innovative design of temporary filters.

Adolescent↗

PubMed2006

Treatment of acute myeloid leukemia patients aged more than 75 years: results of the E-AML-01 trial of the Japanese Elderly Leukemia and Lymphoma Study Group (JELLSG).

The feasibility and effects of combination chemotherapy for very elderly patients with acute myeloid leukemia was examined in 65 patients (including previous myelodysplastic syndrome) aged 76 years or morewith a performance status of 0 - 3. Induction chemotherapy was performed with 30 mg/m2 daunorubicin on days 1 - 3, 150 mg/m2 behenoyl cytosine arabinoside on days 1 - 7, and 70 mg/m2 6-mercaptopurine with 300 mg allopurinol taken orally on days 1 - 7 (BHAC-DM). The complete remission (CR) rate was 38.5%, whereas overall survival at 2 and 5 years was 22.0% and 4.7%, respectively. Two- and 5-year survival of CR patients was 41.8% and 11.2%, respectively. The relapse rate of the 25 CR patients was 64.0% and disease-free survival at 2 and 5 years was 21.0% and 11.2%, respectively. The therapy-related mortality rate at induction was 13.8%. BHAC-DM is feasible and effective for selected very elderly acute myeloid leukemia patients.

Aged↗

PubMed2006

Elevated levels of oxidative DNA damage in serum and myocardium of patients with heart failure.

BACKGROUND: Oxidative stress has been implicated in the pathogenesis of chronic heart failure. The present study investigated whether the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were elevated in the serum and myocardium of patients with dilated cardiomyopathy (DCM), and furthermore whether carvedilol, a vasodilating beta-blocker with antioxidant activity, could reduce the levels. METHODS AND RESULTS: Serum levels of 8-OHdG were measured by enzyme immunoassay in 56 patients with DCM and in 20 control subjects. DCM patients had significantly elevated serum levels of 8-OHdG compared with control subjects. Endomyocardial biopsy samples obtained from 12 DCM patients and 5 control subjects with normal cardiac function were studied immunohistochemically for the expression of 8-OHdG. Positive 8-OHdG staining was found in the nuclei of cardiomyocytes from DCM patients but not in those from control subjects. After treatment with carvedilol, the serum levels of 8-OHdG in DCM patients significantly decreased by 19%, together with amelioration of heart failure. CONCLUSIONS: Levels of 8-OHdG are elevated in the serum and myocardium of patients with heart failure. Treatment with carvedilol might be effective for decreasing the oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2006

Recurrent extramedullary relapse of acute promyelocytic leukemia after allogeneic stem cell transplantation: successful treatment by arsenic trioxide in combination with local radiotherapy.

Isolated extramedullary relapse is rare in patients with acute promyelocytic leukemia (APL) after allogeneic stem cell transplantation (SCT), and an optimal therapy for it has not been established. We describe a patient with APL who developed serially occurring extramedullary disease (EMD) after SCT. We confirmed that EMD had arisen from the recipient's APL blasts by detecting t(15;17) and PML/RARalpha from the tumor cell suspension. The patient displayed EMD 4 times at different sites. Administration of all-trans retinoic acid with local radiotherapy and with chemotherapy for the first to third EMDs resulted in regression of the tumors. However, these regimens did not prevent the subsequent occurrence of new EMD. For the fourth EMD, intravenous administration of arsenic trioxide followed by local radiotherapy resulted in the disappearance of EMD, and no further EMD has developed to date. In the present case, the bone marrow was in morphologic and molecular remission during the course of recurrent EMD. The accumulation of detailed cases is needed to elucidate the pathogenesis, predisposing factors, and optimal therapy for EMD in APL after SCT.

Antineoplastic Agents↗

PubMed2006

L-cysteine inhibits insulin release from the pancreatic beta-cell: possible involvement of metabolic production of hydrogen sulfide, a novel gasotransmitter.

Hydrogen sulfide (H(2)S) was historically recognized as a toxic gas generated by natural resources. However, its enzymatic production from L-cysteine has recently been demonstrated in mammals. Cystathionine beta-synthase and cystathionine gamma-lyase, both of which can produce H(2)S, were expressed in mouse pancreatic islet cells and the beta-cell line, MIN6. L-cysteine and the H(2)S donor NaHS inhibited glucose-induced insulin release from islets and MIN6 cells. These inhibitory effects were reproduced when insulin release was stimulated by alpha-ketoisocaproate, tolbutamide, or high K+. L-cysteine and NaHS inhibited glucose-potentiated insulin release in the copresence of diazoxide and high K+. Real-time imaging of intracellular Ca2+ concentration ([Ca2+](i)) demonstrated that both L-cysteine and NaHS reversibly suppressed glucose-induced [Ca2+](i) oscillation in a single beta-cell without obvious changes in the mean value. These substances inhibited Ca2+ - or guanosine 5'-0-3-thiotriphosphate-induced insulin release from islets permeabilized with streptolysin-O. L-cysteine and NaHS reduced ATP production and attenuated glucose-induced hyperpolarization of the mitochondrial membrane potential. Finally, L-cysteine increased H(2)S content in MIN6 cells. We suggest here that L-cysteine inhibits insulin release via multiple actions on the insulin secretory process through H(2)S production. Because the activities of H(2)S-producing enzymes and the tissue H(2)S contents are known to increase under diabetic conditions, the inhibition may participate in the deterioration of insulin release in this disease.

Animals↗

PubMed2005

Cystathionine beta-synthase is enriched in the brains of Down's patients.

Down's syndrome (DS) or trisomy 21 is the most common genetic cause of mental retardation, and adults with DS develop Alzheimer type of disease (AD). Cystathionine beta-synthase (CBS) is encoded on chromosome 21 and deficiency in its activity causes homocystinuria, the most common inborn error of sulfur amino acid metabolism and characterized by mental retardation and vascular disease. Here, we show that the levels of CBS in DS brains are approximately three times greater than those in the normal individuals. CBS is localized to astrocytes and those surrounding senile plaques in the brains of DS patients with AD. The over-expression of CBS may cause the developmental abnormality in cognition in DS children and that may lead to AD in DS adults.

Adolescent↗

PubMed2005

Constitutively active HIF-1alpha improves perfusion and arterial remodeling in an endovascular model of limb ischemia.

OBJECTIVE: Hypoxia-inducible factor 1 (HIF-1) regulates the expression of angiogenic growth factors. We analyzed the effect of intramuscular (i.m.) delivery of AdCA5, an adenovirus encoding a constitutively active form of the HIF-1alpha subunit, in a novel model of limb ischemia. METHODS: AdCa5 or AdLacZ (6 x 10(8) pfu) was injected into male New Zealand White rabbits that were untreated or subjected to occlusion of the left superficial femoral artery by endovascular coils. Expression of mRNAs was quantified 1, 3, and 7 days after adenovirus injection into rabbits without occlusion. Calf blood pressure (BP), angiography, and immunohistochemical analyses were performed 14 days after arterial occlusion and adenovirus injection. RESULTS: AdCA5 increased the expression of HIF-1alpha, monocyte chemotactic protein-1, placental growth factor, platelet-derived growth factor B, stromal-derived factor 1alpha, and vascular endothelial growth factor (VEGF) mRNA as well as HIF-1alpha and VEGF protein. On day 14, AdCA5-injected limbs showed improved calf BP ratios (0.89+/-0.13 vs. 0.51+/-0.05, p=0.02), angiographic perfusion scores (3.50+/-0.56 vs. 8.33+/-1.31, p=0.007), and distal deep femoral artery diameter ratio (1.84+/-0.25 vs. 0.93+/-0.22, p=0.02) relative to those receiving AdLacZ. The capillary/myocyte ratio (0.93+/-0.03 vs. 0.78+/-0.06, p=0.04) and arterial luminal area (0.32+/-0.05 mm2 vs. 0.21+/-0.03 mm2, p=0.04) were significantly increased in the AdCA5 group. CONCLUSION: In a model that resembles atherosclerotic obstruction of peripheral arteries in patients, the i.m. administration of AdCA5 promoted arteriogenic and angiogenic responses.

Adenoviridae↗

PubMed2005

Cystathionine beta-synthase, a key enzyme for homocysteine metabolism, is preferentially expressed in the radial glia/astrocyte lineage of developing mouse CNS.

Cystathionine beta-synthase (CBS; EC 4.2.1.22) is a key enzyme in the generation of cysteine from methionine. A deficiency of CBS leads to homocystinuria, an inherited human disease characterized by mental retardation, seizures, psychiatric disturbances, skeletal abnormalities, and vascular disorders; however, the underlying mechanisms remain largely unknown. Here, we show the regional and cellular distribution of CBS in the adult and developing mouse brain. In the adult mouse brain, CBS was expressed ubiquitously, but it is expressed most intensely in the cerebellar molecular layer and hippocampal dentate gyrus. Immunohistochemical analysis revealed that CBS is preferentially expressed in cerebellar Bergmann glia and in astrocytes throughout the brain. At early developmental stages, CBS was expressed in neuroepithelial cells in the ventricular zone, but its expression changed to radial glial cells and then to astrocytes during the late embryonic and neonatal periods. CBS was most highly expressed in juvenile brain, and a striking induction was observed in cultured astrocytes in response to EGF, TGF-alpha, cAMP, and dexamethasone. Moreover, CBS was significantly accumulated in reactive astrocytes in the hippocampus after kainic acid-induced seizures, and cerebellar morphological abnormalities were observed in CBS-deficient mice. Taken together, these results suggest that CBS plays a crucial role in the development and maintenance of the CNS and that radial glia/astrocyte dysfunction might be involved in the complex neuropathological features associated with abnormal homocysteine metabolism.

Animals↗

PubMed2005

Determination of oxidized and reduced nicotinamide adenine dinucleotide in cell monolayers using a single extraction procedure and a spectrophotometric assay.

While many investigations measuring oxidized nicotinamide adenine dinucleotide (NAD+) and reduced nicotinamide adenine dinucleotide (NADH) have been carried out on several mammalian tissues and blood cells, few reports have dealt with monolayers of cultured cells. Here we show a novel method to measure NAD+ and NADH in monolayers of a neuroblastoma cell line. The method was established by modifying a single extraction procedure originally developed for erythrocytes and an enzymatic cycling assay using a dye that absorbs in visible range. The following modifications were made. (i) Addition of 0.05% of a detergent, Triton X-100, to carbonate-bicarbonate extraction buffer enabled us to accurately measure cellular [NADH]/([NAD+]+[NADH]). (ii) Addition of N-ethyldibenzopyrazine ethyl sulfate salt (phenazine ethosulfate) immediately before the incubation suppressed the gradual decline of the sensitivity of the assay. The procedure presented here provides a simple and inexpensive measurement of NAD+ and NADH in cell monolayers.

Animals↗

PubMed2005

Functional characterization of five novel CYP2C8 variants, G171S, R186X, R186G, K247R, and K383N, found in a Japanese population.

Cytochrome P450 2C8 is one of the primary enzymes responsible for the metabolism of a wide range of drugs such as paclitaxel, cerivastatin, and amiodarone. We have sequenced the CYP2C8 gene from 201 Japanese subjects and found five novel nonsynonymous single nucleotide polymorphisms (SNPs): 511G>A (G171S), 556C>T (R186X; X represents the translational stop codon), 556C>G (R186G), 740A>G (K247R), and 1149G>T (K383N), with the allele frequency of 0.0025. The CYP2C8 variants were heterologously expressed in COS-1 cells and functionally characterized in terms of expression level, paclitaxel 6alpha-hydroxylase activity, and intracellular localization. The prematurely terminated R186X variant was undetectable by Western blotting and inactive toward paclitaxel 6alpha-hydroxylation. The G171S, K247R, and K383N variants exhibited properties similar to those of the wild-type CYP2C8. Paclitaxel 6alpha-hydroxylase activity of the R186G transfectant was only 10 to 20% that of wild-type CYP2C8. Furthermore, the R186G variant displayed a lower level of protein expression in comparison to the wild type, which was restored by the addition of a proteasome inhibitor (MG-132; Z-Leu-Leu-Leu-aldehyde). The reduced CO-difference spectral analysis using recombinant proteins from an insect cell/baculovirus system revealed that the R186G variant has a minor peak at 420 nm in addition to the characteristic Soret peak at 450 nm, suggesting the existence of improperly folded protein. These results indicate that the novel CYP2C8 SNPs, 556C>T (R186X) and 556C>G (R186G), could influence the metabolism of CYP2C8 substrates such as paclitaxel and cerivastatin.

Animals↗

PubMed2005

Haplotype structures of EPHX1 and their effects on the metabolism of carbamazepine-10,11-epoxide in Japanese epileptic patients.

OBJECTIVE: Microsomal epoxide hydrolase (mEH) is an enzyme that detoxifies reactive epoxides and catalyzes the biotransformation of carbamazepine-10,11-epoxide (CBZ-epoxide) to carbamazepine-10,11-diol (CBZ-diol). Utilizing single nucleotide polymorphisms (SNPs) of the EPHX1 gene encoding mEH, we identified the haplotypes of EPHX1 blocks and investigated the association between the block haplotypes and CBZ-epoxide metabolism. METHODS: SNPs of EPHX1 were analyzed by means of polymerase chain reaction amplification and DNA sequencing using DNA extracted from the blood leukocytes of 96 Japanese epileptic patients, including 58 carbamazepine-administered patients. The plasma concentrations of CBZ and its four metabolites were determined using high-performance liquid chromatography. RESULTS: From sequencing all 9 exons and their surrounding introns, 29 SNPs were found in EPHX1. The SNPs were separated into three blocks on the basis of linkage disequilibrium, and the block haplotype combinations (diplotypes) were assigned. Using plasma CBZ-diol/CBZ-epoxide ratios (diol/epoxide ratios) indicative of the mEH activity, the effects of the diplotypes in each EPHX1 block were analyzed on CBZ-epoxide metabolism. In block 2, the diol/epoxide ratios increased significantly depending on the number of haplotype *2 bearing Y113H (P=0.0241). In block 3, the ratios decreased depending on the number of haplotype *2 bearing H139R (P=0.0351). Also, an increasing effect of a *1 subtype, *1c, was observed on the ratio. CONCLUSION: These results show that some EPHX1 haplotypes are associated with altered CBZ-epoxide metabolism. This is the first report on the haplotype structures of EPHX1 and their potential in vivo effects.

Adolescent↗

PubMed2005

Association study of the chemokine, CXC motif, ligand 1 (CXCL1) gene with sporadic Alzheimer's disease in a Japanese population.

Inflammation is profoundly involved in the development of Alzheimer's disease (AD) and other neurodegenerative diseases. Chemokine, CXC motif, ligand 1 (CXCL1; or GRO1) is an inflammatory cytokine and appears to be implicated in the pathogenesis of AD. It is of interest and importance to see if the CXCL1 gene, mapped on chromosome 4q12-q13, has potential for conferring the predisposition to AD. Here we report on an association study of the CXCL1 gene with sporadic AD patients in a Japanese population; three single nucleotide polymorphisms (SNPs) in the CXCL1 locus were investigated in 103 AD patients and 130 healthy individuals. The results indicate that neither genotype frequencies nor allele frequencies of the examined SNPs attained statistical significance even after being stratified by the presence or absence of the Apolipoprotein E epsilon4 allele. Therefore, the data presented here suggests that the CXCL1 gene could not be associated with the susceptibility to AD in a Japanese population.

Aged↗

PubMed2005

Endovascular model of rabbit hindlimb ischemia: a platform to evaluate therapeutic angiogenesis.

PURPOSE: Current animal hindlimb ischemia models involve surgical ligation of the femoral artery and delivery of therapeutic angiogenic agents into the adductor compartment. The authors hypothesize that an endovascular model of hindlimb ischemia would be a more appropriate platform, closely resembling atherosclerosis by occluding the vessel from within, causing less inflammation, wound healing and subsequent collateralization. MATERIALS AND METHODS: The left superficial femoral artery in 17 rabbits was occluded by endovascular coil embolization (n=9) or surgical ligation (n=8). Animals (n=3; in each group) were sacrificed on day 3 to determine the arteriolar luminal area, number of arterioles, microsphere determined perfusion, and degree of inflammation. On day 28, the remaining animals underwent calf blood pressure measurements and angiography to determine the number of collaterals and diameter of vessels supplying the hindlimb. RESULTS: Immediate postprocedure (day 0) and presacrifice (day 3 or 28) occlusion rates were 89% (eight of nine rabbits) and 100% for the endovascular model; 100% and 100% for the surgical model, respectively. Hindlimb paralysis and muscle atrophy was found in one surgical animal. On day 3, there was an increase in hindlimb perfusion (surgery, 0.04+/-0.01; endovascular, 0.02+/-0.01; P=.02), an increase in arteriolar luminal area (surgery, 481 microm+/-240; endovascular, 345 microm+/-151; P=.04), and a trend toward more inflammation (surgery, 5.5+/-3.8; endovascular, 2.5+/-3.0; P=.08) in the surgical group. There was no difference in number of vessels between both groups. On day 28 there was no difference in the calf blood pressure ratios or in the number of collaterals. However, there was enlargement of the distal profunda femoris artery, the vessel closest to the surgical incision, in the surgical group (L/R ratio: immediate post-occlusion, 1.06+/-0.11; day 28, 1.27+/-0.08; P=.02). CONCLUSION: The endovascular model was efficacious in providing occlusion of the superficial femoral artery, and induced less of an arteriogenic response compared with the surgical model. The authors believe that this endovascular model is a superior platform for studying therapeutic angiogenic agents.

Angiogenesis Inducing Agents↗