Publications (9)33.44 Total impact
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Article: Olmesartan reduces inflammatory biomarkers in patients with stable coronary artery disease undergoing percutaneous coronary intervention: results from the OLIVUS trial.
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ABSTRACT: The OLmesartan on the progression of coronary atherosclerosis: evaluation by IntraVascular UltraSound (OLIVUS) trial demonstrated that an angiotensin II receptor blocker, olmesartan, reduces the rate of coronary atheroma progression as evaluated by intravascular ultrasound in patients with stable angina pectoris undergoing percutaneous coronary intervention. This substudy examined the impact of olmesartan on serum biomarkers and the relationship between biomarker changes and atheroma progression. Patients in the OLIVUS trial (n = 247) were randomly assigned to a control group or the olmesartan group. A subgroup of these patients (n = 135, 55 %) was analyzed at baseline and at 14 months. Patients' characteristics and blood-pressure control were identical between the control group (n = 65) and the olmesartan group (n = 70), and also between the subpopulation and total population. The change in the level of high-sensitivity C-reactive protein (hs-CRP) (mg/l) and adiponectin (μg/ml) was significantly greater in the olmesartan group than in the control group (between-group differences: 0.5 and -0.7; 95 % confidence interval: 0.2-0.8 and -1.3 to -0.1; P = 0.001 and 0.02, respectively). Multiple regression analysis revealed that the nominal changes in total atheroma volume and percent atheroma volume were significantly associated with the nominal change in hs-CRP in the olmesartan group but not in the control group. Olmesartan reduced hs-CRP in patients with stable angina, and this correlated with the change in coronary atheroma.Heart and Vessels 04/2013; · 2.05 Impact Factor -
Article: Four-year clinical outcomes of the OLIVUS-Ex (impact of Olmesartan on progression of coronary atherosclerosis: evaluation by intravascular ultrasound) extension trial.
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ABSTRACT: The previous OLIVUS trial reported a positive role in achieving a lower rate of coronary atheroma progression through the administration of olmesartan, an angiotension-II receptor blocking agent (ARB), for stable angina pectoris (SAP) patients requiring percutaneous coronary intervention (PCI). However, the benefits between ARB administration on long-term clinical outcomes and serial atheroma changes by IVUS remain unclear. Thus, we examined the 4-year clinical outcomes from OLIVUS according to treatment strategy with olmesartan. Serial volumetric IVUS examinations (baseline and 14 months) were performed in 247 patients with hypertension and SAP. When these patients underwent PCI for culprit lesions, IVUS was performed in their non-culprit vessels. Patients were randomly assigned to receive 20-40mg of olmesartan or control, and treated with a combination of β-blockers, calcium channel blockers, glycemic control agents and/or statins per physician's guidance. Four-year clinical outcomes and annual progression rate of atherosclerosis, assessed by serial IVUS, were compared with major adverse cardio- and cerebrovascular events (MACCE). Cumulative event-free survival was significantly higher in the olmesartan group than in the control group (p=0.04; log-rank test). By adjusting for validated prognosticators, olmesartan administration was identified as a good predictor of MACCE (p=0.041). On the other hand, patients with adverse events (n=31) had larger annual atheroma progression than the rest of the population (23.8% vs. 2.1%, p<0.001). Olmesartan therapy appears to confer improved long-term clinical outcomes. Atheroma volume changes, assessed by IVUS, seem to be a reliable surrogate for future major adverse cardio- and cerebrovascular events in this study cohort.Atherosclerosis 11/2011; 220(1):134-8. · 3.79 Impact Factor -
Article: Significant relationship between changes in brachial-ankle pulse wave velocity relative to blood pressure elevation and coronary artery disease.
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ABSTRACT: Based on well-established physiological theories, we studied correlations between changes in brachial-ankle pulse wave velocity (baPWV) relative to blood pressure (BP) elevation (elasticity of large-to-medium-sized arteries), and coronary artery disease (CAD). The baPWV (in centimeters/second) and BP (in millimeters of mercury) were determined in 101 patients before, during, and/or after a cold pressor test using a volume-plethysmographic system. Significantly higher rates of increase in PWV relative to changes in BP were observed in the CAD(+) group than in the CAD(-) group when mean BP [median (25th-75th percentiles): 14.8 (8.3-24.9) vs. 8.6 (5.7-11.4) cm/s/mmHg, P<0.0001], and systolic [10.1 (6.0-17.5) vs. 6.4 (4.4-10.6) cm/s/mmHg, P=0.0023] and diastolic BP [21.0 (14.0-34.4) vs. 10.8 (6.8-16.1) cm/s/mmHg, P<0.0001] were used as BP indices. Similarly, the rates of increase in baPWV showed a significant correlation with the extent of CAD. The rate of increase in baPWV obtained using the mean, systolic and diastolic BP as indices showed an area under the receiver operating characteristic curve of 0.68-0.76, sensitivity of 65-75%, and specificity of 65-75% for the detection of CAD. The area under the receiver operating characteristic curve, sensitivity, and specificity for the rate of increase were slightly higher than those for baseline baPWV and baseline baPWV/baseline BP ratio, but not to a significant degree. The rate of increase in baPWV relative to BP elevation determined by cold pressor test is significantly and moderately correlated with CAD. To identify patients with CAD, the rate of increase in baPWV relative to changes in BP can provide considerable, but limited, information.Coronary artery disease 11/2010; 21(7):407-13. · 1.56 Impact Factor -
Article: Impact of olmesartan on progression of coronary atherosclerosis a serial volumetric intravascular ultrasound analysis from the OLIVUS (impact of OLmesarten on progression of coronary atherosclerosis: evaluation by intravascular ultrasound) trial.
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ABSTRACT: The aim of this study was to evaluate the impact of olmesartan on progression of coronary atherosclerosis. Prior intravascular ultrasound (IVUS) trial results suggest slowing of coronary atheroma progression with some medicines but have not shown convincing evidence of regression with angiotension-II receptor blocking agents. A prospective, randomized, multicenter trial-OLIVUS (Impact of OLmesartan on progression of coronary atherosclerosis: evaluation by IntraVascular UltraSound)-was performed in 247 stable angina pectoris patients with native coronary artery disease. When these patients underwent percutaneous coronary intervention for culprit lesions, IVUS was performed in their nonculprit vessels (without angiographically documented coronary stenosis [<50%]). Patients were randomly assigned to receive 10 to 40 mg of olmesartan or control and treated with a combination of beta-blockers, calcium channel blockers, diuretics, nitrates, glycemic control agents, and/or statins per physician's guidance. Serial IVUS examinations (baseline and 14-month follow-up) were performed to assess coronary atheroma volume. Volumetric IVUS analyses included lumen, plaque, vessel volume, percent atheroma volume (PAV), percent change in total atheroma volume (TAV) and PAV. Patient characteristics and blood pressure control were identical between the 2 groups. However, follow-up IVUS showed significantly decreased TAV and percent change in PAV in the olmesartan group (5.4% vs. 0.6 % for TAV and 3.1% vs. -0.7% for percent change in PAV, control vs. olmesartan, p < 0.05 for all). These observations suggest a positive role in a potentially lower rate of coronary atheroma progression through the administration of olmesartan, an angiotension-II receptor blocking agent, for patients with stable angina pectoris.Journal of the American College of Cardiology 03/2010; 55(10):976-82. · 14.16 Impact Factor -
Article: Higher incidence and serum levels of minor cardiac biomarker elevation in sirolimus-eluting stent (Cypher) than bare metal stent implantations.
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ABSTRACT: Minor cardiac biomarker elevation after percutaneous coronary intervention has long-term prognostic significance. The sirolimus-eluting stent (Cypher) has been reported to require high postinflation pressure for optimal implantation. We examined the incidence of minor cardiac biomarker elevation induced by Cypher implantation. We measured the serum concentration of cardiac troponin-I (cTnI) 24 h after stenting and those of creatine kinase isoenzyme MB and creatine kinase before, immediately after, and 6, 12 and 24 h after implantation in patients who underwent Cypher stent (CS group; n=53) or bare metal stent (BMS group; n=57) implantation. No significant difference in clinical background was observed between the two groups. When a cutoff cTnI value of 0.50 ng/ml was used, the CS group showed a significantly higher incidence of cTnI elevation (35.8%, 19/53) than the BMS group (14.0%, 8/57) (P<0.05). Similarly, the incidence of cTnI > or = 0.03 ng/ml tended to be higher in the CS group (88.7%, 47/53) than in the BMS group (73.7%, 42/57: 0.05<P<0.10). Furthermore, the CS group showed significantly higher cTnI levels than the BMS group (1.32+/-2.38 vs. 0.34+/-0.91 ng/ml. P<0.001). Essentially, similar results were obtained for serum creatine kinase isoenzyme MB and creatine kinase. Among clinical, lesion and procedural characteristics, postinflation pressure for stenting was significantly higher only in the CS group (18.2+/-2.8 atm) than in the BMS group (14.0+/-2.7 atm) (P<0.001). The results demonstrated that CS implantation increases the incidence of minor cardiac biomarker elevation compared with BMS. The difference in postinflation pressure could account for the results.Coronary Artery Disease 04/2008; 19(2):63-9. · 1.24 Impact Factor -
Article: Concomitant expression of heparin-binding epidermal growth factor-like growth factor mRNA and basic fibroblast growth factor mRNA in myocardial infarction in rats.
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ABSTRACT: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is mitogenic and chemotactic for many cell types. HB-EGF is induced in pathological states which require cell mitogenesis and proliferation, including angiogenesis, and has been reported to interact functionally with basic fibroblast growth factor (bFGF). To test our hypothesis that HB-EGF mRNA expression is increased in myocardial infarction, we used Northern hybridization in rats to investigate the expression of HB-EGF and EGF receptor mRNAs expression in the infarct zone compared to the expression of bFGF and FGF receptor mRNAs. We also performed in situ hybridization to identify the cells responsible for HB-EGF mRNA production. HB-EGF mRNA rapidly increased after ligation (mean +/- SE, 5.6+/-0.23-fold increase at 6 hours compared to the preligation heart levels) and reached a maximum level (9.1+/-0.42-fold increase) around 12 hours. HB-EGF mRNA then gradually decreased on day 1 (5.8+/-1.0-fold increase), day 2 (3.2+/-0.94-fold increase) and day 3 (1.9+/-0.33-fold increase) after ligation. Parallel changes in bFGF mRNA expression were observed (6, 12 hours, days 1, 2 and 3; 3.6+/-0.42-, 5.3+/-0.12-, 2.3+/-0.12-, 1.7+/-0.03- and 0.95+/-0.03-fold increase, respectively). EGF receptor (ErbB-1) mRNA was gradually increased on day 2 (2.4+/-0.53-fold increase), day 7(4.0+/-0.61-fold increase) and day 14 (7.0+/-0.61-fold increase). Similarly, FGF receptor (FGF receptor-1) mRNA was gradually increased (days 2,7 and 14; 1.3+/-0.13-, 1.5+/-0.17- and 2.3+/-0.15-fold increase, respectively). Reperfusion after a 2-hour ligation (too late to salvage myocytes) enhanced HB-EGF (12 hours, 16.8+/-1.8-fold increase) and bFGF (12 hours, 10.4+/-1.1-fold increase) mRNA expression. The cells responsible for the increased production of HB-EGF mRNA were shown by in situ hybridization to be surviving myocytes located in the infarct peripheral zone around infarct necrotizing tissue. In conclusion, our results demonstrated a rapid increase in HB-EGF mRNA expression concomitant with an increase in bFGF mRNA expression, suggesting that HB-EGF and bFGF might play some role in the course of pathological changes in the infarct in the early inflammatory phase. Reperfusion at times too late to salvage myocytes accelerated sequential changes in the expression of both HB-EGF and bFGF mRNAs.Archiv für Kreislaufforschung 06/2002; 97(3):214-22. · 7.35 Impact Factor -
Article: Reperfusion accelerates the distribution of type I and III collagen messenger RNA expression after acute myocardial infarction: in situ hybridization in experimental infarction in rats
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ABSTRACT: Background: The effects of reperfusion on the time-dependent appearance and distribution of type I and III collagen messenger RNA (mRNA) expression had not hitherto been examined. Objective: To compare the sequential changes in the extent of distribution of type I and III collagen mRNA expression in reperfused infarct hearts of rats with those in unreperfused infarct hearts. Methods: Using an experimental rat model of infarction, we examined type I and III collagen mRNA expression with specific rat pro [alpha]1(I) and human pro [alpha]1(III) collagen riboprobes by in-situ hybridization. Reperfusion was established after a 2h coronary ligation that produced complete necrosis of the myocytes. Results: Positive signals both for [alpha]1(I) and for [alpha]1(III) collagen mRNA appeared in the infarct peripheral zone 12h after coronary ligation both of the reperfused and of unreperfused hearts. The spread of signal into the infarct central zone occurred 1-2 days earlier for the reperfused hearts than it did for the unreperfused hearts. The difference between the distributions of signals for the reperfused and unreperfused hearts became obscure on day 14. No notable difference between the extents of signal distribution for [alpha]1(I) and [alpha]1 (III) collagen mRNA was obtained. We observed intense signals from spindle-shaped mesenchymal cells (myofibroblasts and fibroblasts) located between surviving myocytes in the marginal zone of the infarct. No myocyte exhibited signals both for [alpha]1(I) and for [alpha]1(III) collagen mRNA. Conclusion: In the present study, using in-situ hybridization, we demonstrated that reperfusion accelerates the distribution of expression both of [alpha]1(I) and of [alpha](III) collagen mRNA in the infarct zone after acute myocardial infarction in rats. (C) 1999 Lippincott Williams & Wilkins, Inc.Coronary Artery Disease 08/1999; 10(2). · 1.24 Impact Factor -
Article: Spatially and temporally different expression of osteonectin and osteopontin in the infarct zone of experimentally induced myocardial infarction in rats.
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ABSTRACT: Osteonectin and osteopontin, two secreted matricellular proteins, have a variety of functions that are exerted through interaction with matrix components. These proteins appear in response to tissue injury. To test our hypothesis that osteopontin and osteonectin are expressed with spatially and temporally different patterns in myocardial infarct tissue, we investigated osteonectin and osteopontin expression in experimentally induced myocardial infarction in rats, in comparison with Type I collagen expression. Northern blotting demonstrated that osteonectin mRNA did not markedly increase on Day 2 after the infarction, but it increased on Days 7 and 14 by 1.7+/-0.12- and 1.8+/-0.01-fold compared to that in preligation hearts. In contrast, osteopontin mRNA was increased on Day 1 (41.9+/-11.3-fold increase) and on Day 2 (58.3+/-7.6-fold increase), and then it declined on Days 7 and 14 (24.8+/-9.0- and 13.5+/-4.7-fold increase, respectively). In situ hybridization revealed that osteonectin mRNA signals were observed in fibroblasts, myofibroblasts and macrophages around infarct necrotic tissue on Days 7 and 14. Osteopontin mRNA signals were observed in macrophages in the infarct marginal zone on Day 2. Immunopositive staining for both osteonectin and osteopontin showed the same pattern as that obtained by in situ hybridization. The time course of osteonectin mRNA was almost parallel with that of Type I collagen mRNA, while that of osteopontin was not. These results demonstrated spatially and temporally different expression patterns of osteonectin and osteopontin in myocardial infarction and suggest that osteonectin appears to be involved in the pathological course in the late phase after infarction concomitantly with Type I collagen, while osteopontin may play a role in the early phase.Cardiovascular Pathology 12(4):186-94. · 2.07 Impact Factor -
Article: Expression of Perlecan Proteoglycan in the Infarct Zone of Mouse Myocardial Infarction
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ABSTRACT: M. Nakahama, T. Murakami, S. Kusachi, I. Naito, K. Takeda, H. Ohnishi, I. Komatsubara, T. Oka, Y. Ninomiya and T. Tsuji. Expression of Perlecan Proteoglycan in the Infarct Zone of Mouse Myocardial Infarction. Journal of Molecular and Cellular Cardiology (2000) 32, 1087–1100. Perlecan, a basal lamina proteoglycan, has been shown to interact with other extracellular matrix (ECM) components, especially type IV collagen, and is thus involved in ECM formation. Perlecan has also been postulated to promote growth factor-receptor interactions, including the binding of basic fibroblast growth factor (bFGF) to its receptor, and to enhance mitogenesis and angiogenesis. To test our hypothesis that perlecan is increased in the myocardial infarct zone, we examined perlecan expression after experimentally induced myocardial infarction in BALb/c mice by the methods of in situ hybridization, Northern blotting, and immunohistochemistry. In situ hybridization revealed mRNA signals for perlecan in the infarct marginal zone on day 2 and in the infarct interior zone around infarct granulation tissue on day 7. On day 14 the signals were observed at the center point of the infarct. The signals were detected in spindle-shaped mesenchymal cells (fibroblasts and myofibroblasts). Some surviving myocytes in the infarct marginal zone also showed positive signals. The sequential changes in the perlecan mRNA signal distribution paralleled those for type IV collagen mRNA. Northern blotting demonstrated increased expression of perlecan consistent with the observations of in situ hybridization. Immunopositive staining for perlecan was observed in the infarct zone around granulation tissue on day 7 and in the entire infarct zone on days 14–28. Immunostaining for bFGF was localized surrounding the infarct granulation tissue on day 7 and overlapped with perlecan immunostaining. The present results demonstrated the expression of perlecan by spindle-shaped mesenchymal cells (fibroblasts and myofibroblasts) and some surviving myocytes in the myocardial infarct, indicating the contribution of perlecan to the pathological course of myocardial infarction.Journal of Molecular and Cellular Cardiology.
