Biomedical subjects

Naotaka Maeda

Publications and source records attributed to Naotaka Maeda.

7 recordsLinked to original sources

PubMed2006

Feasibility and safety of thrombectomy with TVAC aspiration catheter system for patients with acute myocardial infarction.

Early reperfusion with angioplasty and stenting is established as a central, effective treatment for acute myocardial infarction (AMI). The role of thrombectomy prior to angioplasty remains to be elucidated. To evaluate its feasibility, safety, and efficacy, thrombectomy using a TVAC aspiration catheter system was attempted prior to angioplasty and stenting in 40 consecutive patients with AMI. Fifty consecutive patients with AMI in whom angioplasty and stenting were performed without prior thrombectomy served as controls. Neither distribution of Killip classification nor culprit lesion was different between the two groups. In patients treated with the TVAC system, the procedure was successful in 39/40 patients (98%) and there were no procedure-related complications. In the final coronary angiogram, TIMI-3 (Thrombolysis in Myocardial Infarction) flow was obtained in 37/40 (93%) in patients treated with the TVAC system and 43/50 (86%) in control patients. Electrocardiograms before and after coronary intervention were analyzed in patients with ST elevation AMI (35 patients treated with the TVAC system and 41 control patients). ST elevation recovery >50% of the initial value was observed after coronary intervention in 26/35 (74%) in patients treated with the TVAC system and 26/41 (63%) in control patients (P = 0.33). In the case of anterior AMI, ST elevation recovery >50% of the initial value was observed in 13/17 (76%) in patients treated with the TVAC system and 8/20 (40%) in control patients (P = 0.045). Thus, thrombectomy using a TVAC system is feasible, safe, and may have the potential to enhance ST-segment resolution in patients with anterior AMI.

Aged↗

PubMed2006

Effect of vasoconstrictor coupling factor 6 on gene expression profile in human vascular endothelial cells: enhanced release of asymmetric dimethylarginine.

BACKGROUND: Coupling factor 6 (CF6), a component of ATP synthase, inhibits phospholipase A2 and induces vasoconstriction. However, because arachidonic acid acts in the widespread fields of vascular biology, CF6 might exert profound effects in addition to vasoconstriction. We investigated the effect of CF6 on the gene expression profile in human umbilical vein endothelial cells. METHODS AND RESULTS: The increased gene expression after 24-h exposure to CF6 at 10 mol/l, assessed by cDNA microarray (n = 3), included neuregulin-1 (1.84 +/- 0.07 fold compared with control, P < 0.05) and relaxin-1 (1.74 +/- 0.20, P < 0.05), both relating to congestive heart failure, urokinase type plasminogen activator receptor (1.77 +/- 0.24, P = 0.06) and estrogen receptor beta (1.74 +/- 0.36, P = 0.08), both relating to vascular inflammation and cell infiltration, and protein arginine methyltransferase (PRMT-1; 1.73 +/- 0.20, P < 0.05). Out of these genes, the enzyme relating to the synthesis (PRMT-1) of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), was further examined concomitantly with the degradation enzyme, dimethylarginine dimethylaminohydrolase 2 (DDAH-2). The ratio of PRMT-1 to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA, measured by real-time quantitative reverse transcription-polymerase chain reaction, was increased by 9 +/- 2% (n = 10, P < 0.01) at 48 h after CF6 at 10 mol/l, whereas the ratio of DDAH-2 to GAPDH was decreased by 12 +/- 2% (n = 8, P < 0.01). DDAH-2 protein and activity were decreased by 28 +/- 5% (n = 5, P < 0.01) and 19 +/- 2% (n = 6, P < 0.01) by CF6, respectively. ADMA release was enhanced by 20 +/- 8% and NOS activity was decreased by 13 +/- 1% (both n = 8, P < 0.05) by CF6. CONCLUSIONS: CF6 changes the gene expression profile to be proatherogenic and functions as a novel stimulator for ADMA release by enhancing its synthesis and suppressing its degradation.

Amidohydrolases↗

PubMed2005

Intracellular signaling for vasoconstrictor coupling factor 6: novel function of beta-subunit of ATP synthase as receptor.

Coupling factor 6 (CF6), a component of adenosine triphosphate (ATP) synthase, is circulating and functions as an endogenous vasoconstrictor by inhibiting cytosolic phospholipase A2. We showed a high plasma level of CF6 in human hypertension. The present study focused on the identification and characterization of a receptor for CF6 and its post-receptor signaling pathway. Incubation of human umbilical vein endothelial cells (HUVECs) with an excess of free CF6 reduced by 50% the immunoreactivity for the antibody to beta-subunit of ATP synthase at the cell surface, but unaffected that for the alpha-subunit antibody. A significant displacement of radioligand was observed at 3x10(-9) through 10(-7) M unlabeled CF6, and the Kd was 7.6 nM. Adenosine diphosphate (ADP) at 10(-7) M and beta-subunit antibody suppressed the binding of (125)I-CF6 by 81.3+/-9.7% and 32.0+/-2.0%, respectively, whereas the alpha-subunit antibody unaffected it. The hydrolysis activity of ATP to ADP was increased by 1.6-fold by CF6 at 10(-7) M, and efrapeptin at 10(-5) M, an inhibitor of ATP synthase, blocked it. CF6 at 10(-7) M decreased intracellular pH in 2',7'-bis(carboxyethyl-5 (6))-carboxyfluorescein-loaded HUVEC. Amyloride at 10(-4) M augmented the pH decrease in response to CF6, whereas efrapeptin at 10(-5) M blocked it. Arachidonic acid release was suppressed by CF6, and it was reversed by efrapeptin at 10(-5) M or beta-subunit antibody or ADP at 10(-7) M. The beta-subunit antibody suppressed coupling factor 6-induced increase in blood pressure. These indicate that membrane-bound ATP synthase functions as a receptor for CF6 and may have a previously unsuspected role in the genesis of hypertension by modulating the concentration of intracellular hydrogen.

Arachidonic Acid↗

PubMed2005

Roxithromycin is an inhibitor of human coronary artery smooth muscle cells proliferation: a potential ability to prevent coronary heart disease.

Roxithromycin (RXM), a macrolide antibiotic, is used in clinical trials to address secondary prevention of coronary heart disease. However, the effects of RXM on human coronary artery smooth muscle cells (CASMC) proliferation remain unclear. Human CASMC were stimulated with growth medium containing 5% fetal bovine serum and growth factors. RXM at 1 or 10 microg/ml, which are relevant to the therapeutic plasma levels, significantly suppressed mitogen-induced CASMC proliferation, assessed by WST-1 assay and cell counting. Flow cytometry analysis demonstrated that RXM suppressed mitogen-induced G1 to S progression on cell cycle. Western blot showed that RXM inhibited phosphorylation of retinoblastoma gene products, reduced protein levels of cyclin D1 and A, and restored downregulation of cyclin-dependent kinase (CDK) inhibitor p27kip1. The activities of CDK4 and CDK2 were suppressed by RXM without affecting their protein levels. When transfected with both IkappaB kinase alpha and beta constructs as nuclear factor-kappa B (NF-kappaB) activator, CASMC entered S phase at 24 h, and RXM inhibited it. Electrophoretic mobility shift assay and immunostaining of NF-kappaB p65 demonstrated that RXM inhibited mitogen-induced NF-kappaB activation. These results indicate that RXM is an inhibitor of human CASMC proliferation through modulating cell cycle regulatory proteins and inhibiting NF-kappaB signaling pathway.

Anti-Bacterial Agents↗

PubMed2005

Troglitazone and 15-deoxy-delta(12,14)-prostaglandin J2 inhibit shear-induced coupling factor 6 release in endothelial cells.

OBJECTIVE: We previously showed that mitochondrial coupling factor 6 (CF6), an endogenous inhibitor of prostacyclin synthesis and a vasoconstrictor, is present on the surface of human umbilical vein endothelial cells (HUVEC) and is released outside of the cells by shear stress. We investigated the intracellular signaling mechanism for shear-induced release of CF6 in HUVEC and the effects of troglitazone and 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2), both peroxisome proliferator-activated receptor (PPAR)-gamma ligands, on it. METHODS AND RESULTS: The release and gene expression of CF6 in HUVEC were enhanced by shear stress at 25 dyn/cm2, measured by radioimmunoassay and real-time RT-PCR, respectively. The intracellular content of CF6 was decreased after exposure to shear stress at 25 dyn/cm2. Transfection experiments with deletional and mutational CF6 promoter constructs, and with dominant negative mutant IkappaB kinase alpha (K44M) demonstrated that shear-induced CF6 transcription was dependent on nuclear factor-kappa B (NF-kappaB) activation. Pretreatment with troglitazone or 15d-PGJ2 inhibited the shear-induced release and gene expression of CF6, whereas fenofibric acid, a PPAR-alpha ligand, had no influence on them. Western blot and immunostaining showed that troglitazone and 15d-PGJ2 inhibited the shear-induced, reactive oxygen species (ROS)-mediated activation of NF-kappaB at the level of IkappaB protein. CONCLUSIONS: The shear-induced gene expression and release of CF6 in HUVEC are mediated by the ROS-related activation of NF-kappaB signaling pathway. Troglitazone and 15d-PGJ2 inhibit them at the IkappaB protein level.

Blotting, Western↗

PubMed2005

Enalapril suppresses ventricular remodeling more effectively than losartan in patients with acute myocardial infarction.

BACKGROUND: Ventricular remodeling after acute myocardial infarction (AMI) is associated with increased morbidity and mortality. ELITE II study showed that losartan, an angiotensin receptor blocker, shows a survival benefit to the same degree as captopril, an angiotensin-converting enzyme inhibitor, does in patients with heart failure. However, recent OPTIMAAL study showed that clinical outcomes after losartan are not superior to those after captopril in patients with AMI. We examined the effect of losartan on ventricular remodeling after AMI comparatively with that of enalapril. METHODS: We enrolled 203 consecutive patients with AMI (mean age 62 +/- 11 years). All patients underwent primary percutaneous coronary intervention and were randomly assigned to losartan (25-50 mg, n = 101) or enalapril (2.5-10 mg, n = 102) treatment. Biplane left ventriculography was performed just after primary percutaneous transluminal coronary angioplasty (acute phase) and 6 months after the onset of AMI. RESULTS: Any of the maximal creatine kinase level, left ventricular end-diastolic volume index, end-systolic volume index, and ejection fraction measured at acute phase was not different between losartan and enalapril groups. However, changes in left ventricular end-diastolic index (18 +/- 25 vs 8 +/- 24 mL/m2) and left ventricular end-systolic volume index (10 +/- 20 vs 2 +/- 18 mL/m2) from acute phase to 6 months were significantly greater in losartan than in enalapril group. Change in left ventricular ejection fraction (0.2% +/- 10.3% vs 3.4% +/- 11.6%) from acute phase to 6 months was significantly smaller in losartan than in enalapril group. The plasma level of brain natriuretic peptide at 6 months was significantly higher in losartan than in enalapril group (all P < .05). CONCLUSION: These indicate that enalapril suppresses ventricular remodeling after AMI more effectively than losartan.

Angioplasty, Balloon, Coronary↗

PubMed2005

Nocturnal blood pressure decrease is associated with increased regional cerebral blood flow in patients with a history of ischemic stroke.

BACKGROUND: It remains controversial whether there is a J-shaped relationship between blood pressure and recurrent stroke among patients with a recent history of ischemic stroke. OBJECTIVE: To investigate the relationship between regional cerebral blood flow (rCBF) and the dipping of nocturnal blood pressure in patients receiving antihypertensive treatment after ischemic stroke. METHODS AND RESULTS: Forty-seven patients with a previous history of ischemic stroke and 37 patients with a history of non-ischemic stroke underwent 24-h ambulatory blood pressure monitoring and rCBF measurement with single photon emission computed tomography. Of the 47 patients with ischemic stroke, 30 were diagnosed as having suffered atheromatous or embolic stroke, and 37 had an ischemic lesion in the territory of the carotid artery. Systolic and diastolic blood pressures during daytime and night-time were controlled at less than 140/90 mmHg by a low-salt diet or long-acting antihypertensive agents, or both. In patients with ischemic stroke, there were significant negative correlations between the percentage change in nocturnal blood pressure and rCBFs in the thalamus (r = -0.33, P = 0.02), putamen (r = -0.34, P = 0.02) and cerebral cortex (r = -0.31, P = 0.03). Multivariate analysis revealed that only the percentage change in nocturnal blood pressure was related to rCBF. There was a significant positive correlation between rCBFs in the thalamus and the cerebral cortex (r = 0.74, P < 0.05). In patients with non-ischemic stroke, there was no significant correlation between the percentage change in nocturnal blood pressure and rCBFs. CONCLUSIONS: These findings indicate that the decrease in nocturnal blood pressure is associated with the increase in rCBF in patients with a history of ischemic stroke in the territory of the carotid artery.

Adult↗