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Biomedical subjects

Katsusuke Yano

Publications and source records attributed to Katsusuke Yano.

At least 19 recordsLinked to original sources

Fibrotic response to angiotensin II is blunted in the kidney, but not in the heart, in insulin-sensitive long-lived transgenic dwarf rats.

Insulin resistance is a characteristic feature of cardiovascular and renal diseases, and angiotensin II (Ang II) has been suggested to induce insulin resistance. The aims of this study were to elucidate the effect of chronic Ang II infusion on vascular reactivity and organ damage in insulin-sensitive rats. We confirmed the following three points. First, there was no significant difference in pressor response to chronic Ang II infusion (600 ng/kg/min) between insulin-sensitive transgenic rats (Tg) and control rats (C). Second, there was no significant difference in cardiac hypertrophy and fibrosis by chronic Ang II infusion between the two groups. However, third, fibrotic response to chronic Ang II infusion evaluated by histopathological scoring in the kidney was significantly decreased in insulin-sensitive transgenic rats (renal fibrosis and nephropathy score: C+Ang II vs Tg+Ang II; 2.5 vs 1.3; p<0.05). Furthermore, the expression of TGF-beta, a fibrosis indicator, was also significantly suppressed in the kidneys of the transgenic rats (TGF-beta1/GAPDH ratio: C+Ang II vs Tg+Ang II; 1.15 vs 0.81; p<0.05). This result indicates that the growth hormone/insulin-like growth factor-1 axis is critically involved in the development of renal injury and fibrosis, rather than hypertension, cardiac hypertrophy, and cardiac fibrosis induced by chronic Ang II administration.

Angiotensin II↗

Risk of development of abdominal aortic aneurysm and dissection of thoracic aorta in a postpartum woman with Marfan's syndrome.

A 24-year-old pregnant woman with Marfan's syndrome delivered by cesarean section during the 38th week of gestation. Although aortic root dilatation did not increase during pregnancy, three months after delivery, the patient noticed a pulsatile abdominal mass. Aortic aneurysm was diagnosed and surgical replacement of the infrarenal abdominal aorta to the common iliac arteries and reconstruction of the inferior mesenteric artery were performed. Moreover, the patient subsequently developed a Stanford type B thoracic aortic dissection, even after more than four months of beta-blockade.

Adrenergic beta-Antagonists↗

Glutaredoxin modulates platelet-derived growth factor-dependent cell signaling by regulating the redox status of low molecular weight protein-tyrosine phosphatase.

Glutaredoxin (GRX) is a glutathione-disulfide oxidoreductase involved in various cellular functions, including the redox-dependent regulation of certain integral proteins. Here we demonstrated that overexpression of GRX suppressed the proliferation of myocardiac H9c2 cells treated with platelet-derived growth factor (PDGF)-BB. After stimulation with PDGF-BB, the phosphorylation of PDGF receptor (PDGFR) beta was suppressed in GRX gene-transfected cells, compared with controls. Conversely, the phosphorylation was enhanced by depletion of GRX by RNA interference. In this study we focused on the role of low molecular weight protein-tyrosine phosphatase (LMW-PTP) in the dephosphorylation of PDGFRbeta via a redox-dependent mechanism. We found that depletion of LMW-PTP using RNA interference enhanced the PDGF-BB-induced phosphorylation of PDGFRbeta, indicating that LMW-PTP works for PDGFRbeta. The enhancement of the phosphorylation of PDGFRbeta was well correlated with inactivation of LMW-PTP by cellular peroxide generated in the cells stimulated with PDGF-BB. In vitro, with hydrogen peroxide treatment, LMW-PTP showed decreased activity with the concomitant formation of dithiothreitol-reducible oligomers. GRX protected LMW-PTP from hydrogen peroxide-induced oxidation and inactivation in concert with glutathione, NADPH, and glutathione disulfide reductase. This strongly suggests that retention of activity of LMW-PTP by enhanced GRX expression suppresses the proliferation of cells treated with PDGF-BB via enhanced dephosphorylation of PDGFRbeta. Thus, GRX plays an important role in PDGF-BB-dependent cell proliferation by regulating the redox state of LMW-PTP.

Animals↗

Effects of antiarrhythmic drugs on apoptotic pathways in H9c2 cardiac cells.

Antiarrhythmic drugs may induce cellular apoptosis in the heart. By using representatives of 5 different categories of antiarrhythmic drugs, that is, pilsicainide, propranolol, nifekalant, verapamil, and amiodarone, we investigated whether these ion channel blockers or beta-antagonists affect cardiac apoptosis in cell cultures. Cultured H9c2 cells were treated with the drugs at varying concentrations. To determine the degree of apoptosis, the percentage of hypodiploid cells, mitochondrial transmembrane potential (DeltaPsi(m)), and activities of caspases were measured quantitatively. At 24 h after administration, only amiodarone induced apoptosis in the H9c2 cells. Amiodarone at a concentration of 14.8 microM or higher decreased DeltaPsi(m) and activated caspase-2 within 3 h of administration, and it caused the appearance of hypodiploid cells and activation of caspases-3 and -9 at 6 h or later. Thus, amiodarone, but none of the other antiarrhythmic drugs tested, possesses a pro-apoptotic effect, mainly via the mitochondrial pathway, suggesting that this effect is distinct from the blocking action of Na+, K+, and Ca2+ channels or the beta-adrenergic receptor. Furthermore, induction of apoptosis in a dose-dependent manner by amiodarone indicates the importance of monitoring the serum concentration in order to avoid its adverse effects.

Amiodarone↗

Prognostic significance of incident complete left bundle branch block observed over a 40-year period.

This case-control study was designed to assess the incidence and mortality of complete left bundle branch block (LBBB). We investigated 17,361 subjects (6,663 men and 10,698 women) who underwent biennial health examinations, including electrocardiography and cardiothoracic ratio measurements from 1958 to 2002. A total of 110 incident LBBB cases (41 men and 69 women) were observed, and their basic characteristics were compared with those of 456 age- and gender-matched controls (156 men and 300 women). Also, the possible association between LBBB and all-cause and cause-specific mortality was examined using a Cox proportional hazard model adjusted for age, gender, and underlying disease. The average age at LBBB diagnosis was 69.6 +/- 10.0 years in men and 68.3 +/- 10.9 years in women, and the incidence of LBBB increased progressively with age. Also, underlying disease, hypertension, and ischemic heart disease were significantly associated with LBBB. The cardiothoracic ratio was significantly different at the diagnosis of LBBB between those with LBBB and controls. Electrocardiographic manifestations before LBBB diagnosis included a higher rate of left ventricular hypertrophy and ST-T abnormalities in patients with LBBB. On Cox analysis, LBBB did not predict for all-cause mortality, but it did predict for mortality from congestive heart failure. In conclusion, the mean patient age at LBBB diagnosis was relatively elderly, and the LBBB incidence increased progressively with advancing age. Hypertension, ischemic heart disease, left ventricular hypertrophy, ST-T abnormalities, and an increased cardiothoracic ratio were associated with LBBB. LBBB predicted for mortality from heart failure but not for all-cause mortality, independent of age, gender, and underlying disease.

Adult↗

Contribution of central nitric oxide to the regulation of blood pressure and sodium balance in DOCA-salt hypertension.

We examined whether central nitric oxide is involved in blood pressure (BP) regulation in deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt rats were intracerebroventricularly infused (ICV) NG-monomethyl L-arginine (L-NMMA) for 4 weeks at either low (0.08 mg/kg/d; n = 8) or high (0.16 mg/kg/d; n = 8) dose. Saline ICV (n = 9) and intraperitoneal infused L-NMMA (low, n = 6; high dose, n = 6) were served as controls. Also, L-NMMA ICV (low, n = 6; high dose, n = 6) was conducted in normal rats. At week 3 and after, DOCA-salt with low L-NMMA ICV showed a higher BP than saline ICV (at week 4: 167.4 +/- 3.6 vs. 150.3 +/- 3.9 mm Hg, P < 0.01); this difference of BP was cancelled after ganglionic block. High L-NMMA ICV did not affect the trend of BP; however, it caused a reduced amount of saline drinking and a less estimated sodium retention than saline or low L-NMMA ICV (for 3 wk; 47.5 +/- 1.1 vs. 66.0 +/- 3.7 and 61.7 +/- 2.5 mmol, P < 0.01). In normal rats, high, but not low, L-NMMA ICV elevated BP with no effect on drinking behavior. Intraperitoneal infused L-NMMA did not affect the development of hypertension and/or sodium balance. These data suggested that, in DOCA-salt, central nitric oxide is involved in BP regulation through the dual action on sympathetic nervous activity and sodium balance.

Animals↗

Angiotensin-converting enzyme inhibitor suppresses the incidence of prolonged and fractionated right atrial electrograms.

INTRODUCTION: Although prolonged and fractionated right atrial electrograms have been reported as predictors of the development of chronic atrial fibrillation in patients with paroxysmal atrial fibrillation (PAF), the effects of angiotensin-converting enzyme inhibitor (ACEI) on these electrophysiologic abnormalities remain unknown. The purpose of this study was to evaluate whether ACEI influences these electrophysiologic abnormalities of atrial muscle in patients with PAF. METHODS: While taking oral ACEI for hypertension, 12 patients (ACEI group) with PAF underwent electrophysiologic study (EPS). Catheter mapping of 12 right atrial sites and right atrial extrastimulation were performed during sinus rhythm. Twenty-four age-matched patients with PAF but not taking oral ACEI were included as a control group. RESULTS: The longest duration of the right atrial electrogram was significantly shorter and the maximum number of fragmented deflections per patient was significantly lower in the ACEI group than in the control group (79 +/- 15 ms vs 100 +/- 15 ms, P < 0.005; 5.5 +/- 1.9 vs 7.9 +/- 2.4, P < 0.001, respectively). The number of abnormal atrial electrograms per patient was significantly lower in the ACEI group than in the control group (0.5 +/- 1.4 vs 2.1 +/- 1.8, P < 0.05). The percentage of patients with at least one abnormal atrial electrogram was significantly lower in the ACEI group than in the control group (16.7% vs 79.2%, P < 0.0005). CONCLUSIONS: ACEI use is associated with a decrease in the incidence of prolonged and fractionated right atrial electrograms in patients with PAF. In addition, we suggest that ACEI may help prevent PAF from becoming chronic.

Angiotensin-Converting Enzyme Inhibitors↗

Pravastatin decreases blood pressure in hypertensive and hypercholesterolemic patients receiving antihypertensive treatment.

BACKGROUND: Previous studies have suggested that the lipid-lowering agents, statins, may help reduce blood pressure (BP). The goal of the present study was to characterize the effect of pravastatin on BP in hypercholesterolemic and hypertensive patients already receiving antihypertensive drugs. METHODS AND RESULTS: Eighty-two patients with hypercholesterolemia were retrospectively studied before and after 3 months of treatment with pravastatin. Forty-four patients had hypertension (HT group) and were receiving antihypertensive treatment, while the remaining 38 patients were normotensive (NT group). Patients in the HT group were further subdivided into those with uncontrolled or controlled BP. Pravastatin treatment significantly reduced systolic BP (SBP) in the HT group (134+/-16 to 130+/-13 mmHg, p<0.005) but not in the NT group (124+/-10 to 123+/-9 mmHg, p=0.52), despite the fact that treatment significantly reduced low-density lipoprotein cholesterol in both groups (HT group 178+/-27 to 132+/-17 mg/dl, p<0.0001; NT group 169+/-27 to 125+/-21 mg/dl, p<0.0001). Further, pravastatin significantly decreased SBP in the uncontrolled BP group (148+/-7 to 138+/-12 mmHg, p<0.005) but not in the controlled BP group (122+/-10 to 123+/-9 mmHg, p=0.72). CONCLUSION: Concomitant use of statins and antihypertensive drugs could result in improved BP control in hypertensive patients with hypercholesterolemia.

Adult↗

Predictors of sub-acute stent thrombosis in acute myocardial infarction patients following primary coronary stenting with bare metal stent.

BACKGROUND: The aim of the present study was to identify the relationship between sub-acute stent thrombosis (SAT) and acute-phase inflammatory reactants, such as high-sensitivity C-reactive protein (hs-CRP) and serum amyloid-A protein (SAA), in patients with acute myocardial infarction (AMI) successfully treated with primary coronary stenting. METHODS AND RESULTS: The 381 consecutive AMI subjects were reperfused by primary coronary stenting within 24 h of onset. SAT was confirmed angiographically in 10 patients (2.6%). There were no significant differences between the patients with or without SAT in terms of patient characteristics, Killip classification on admission, or stent diameter, nor were there significant differences between the 2 groups in terms of left ventricular function soon after stenting (left ventricular ejection fraction) or end-diastolic volume index. The plasma levels of both hs-CRP and SAA were significantly higher in the SAT patients than in the others (hs-CRP: 6.7+/-6.7 mg/dl vs 3.3+/-3.8 mg/dl, p=0.007; SAA: 699+/-812 mug/dl vs 208+/-273 mug/dl, p<0.0001). Multivariate analysis identified SAA as an independent predictor of SAT (risk ratio: 4.9, 95% confidence interval: 1.7-14.9, p<0.05). CONCLUSION: In patients with AMI who are treated with primary coronary stenting, inflammation may be closely related to SAT, for which SAA is a useful predictor.

Acute Disease↗

Serum amyloid a protein as a predictor of cardiac rupture in acute myocardial infarction patients following primary coronary angioplasty.

BACKGROUND: The predictors of cardiac rupture (CR) in patients with acute myocardial infarction (AMI) treated with successful primary coronary angioplasty have not been identified. METHODS AND RESULTS: Of 433 consecutive AMI subjects who underwent reperfusion by primary coronary angioplasty within 24 h of onset, CR occurred in 11 (2.5%), free wall rupture in 9, and ventricular septal perforation in 2. Rates of females, diabetes mellitus and anterior infarction were higher in the group of CR patients than in the others (p < 0.05). There were no significant differences between the 2 groups in terms of left ventricular (LV) function soon after recanalization, such as LV ejection fraction, regional wall motion, or end-diastolic volume index. Plasma levels of both high-sensitivity C-reactive protein (hsCRP) and serum amyloid-A protein (SAA) were significantly higher in the CR patients than in the others (hsCRP: 6.7 +/- 6.7 mg/dl vs 3.3 +/- 3.8 mg/dl, p = 0.007; SAA: 699 +/- 812 microg/dl vs 208 +/- 273 microg/dl, p < 0.0001). Multivariate analysis identified SAA as an independent predictor of CR (risk ratio: 8.8, 95% confidence interval: 1.7-25.6, p < 0.05). Conclusions In patients with AMI treated with primary coronary angioplasty, inflammation may be closely related to CR, for which SAA is a useful predictor.

Aged↗

Accumulation of risk factors increases risk of thromboembolic events in patients with nonvalvular atrial fibrillation.

BACKGROUND: Accumulation of risk factors could increase thromboembolic event rates in patients with nonvalvular atrial fibrillation (NVAF). To validate this hypothesis, a post hoc analysis was performed to determine the relationship of risk levels and thromboembolic events in patients with NVAF from our previous prospective study. METHODS AND RESULTS: Risk levels were quantified using the CHADS2 index in 509 patients with NVAF (66.3+/-10.3 years old). One point each was given for patients with advanced age (>or=75 years), hypertension, congestive heart failure, and diabetes mellitus, and 2 points, to those with prior ischemic stroke or transient ischemic attack. Patients with a CHADS2 score of 0 were classified as low risk, 1 to 2 a moderate risk and 3 or more were high risk. Because hypertrophic cardiomyopathy had emerged as an independent risk factor for thromboembolism, the original CHADS2 score was modified by adding 1 point to patients with hypertrophic cardiomyopathy. Warfarin was given to 263 patients (mean international normalized ratio (INR) at enrollment, 1.86), antiplatelets (aspirin or ticlopidine) to 163 patients and no antithrombotic therapy to 83. During a mean follow-up period of 2 years, 31 thromboembolic events occurred. As the risk level (modified CHADS2 score) increased, the event rate increased for both the patient groups receiving warfarin (p=0.035) and those not receiving warfarin (p=0.048). When a thromboembolic event occurred in patients who had been treated with warfarin, the mean INR level was 1.41. Twelve (75%) of 16 patients complicated with thromboembolism during warfarin treatment had INR levels below the optimal levels (1.6-2.6) for Japanese patients. CONCLUSION: Accumulation of risk factors could increase risk of thromboembolic events in patients with NVAF. Adherence to the guidelines for anticoagulation therapy is recommended.

Aged↗

Long-Term follow-up of the circadian rhythm of heart rate and heart rate variability in healthy elderly patients.

BACKGROUND: The long-term age-related changes in circadian rhythm of heart rate variability (HRV), that is, autonomic nervous activity, remain unknown in elderly people. METHODS AND RESULTS: Holter monitoring was conducted twice at an interval of 15 years in 15 healthy elderly patients (age: 70.0 +/- 4.1 years, at first monitoring, female: 10) and assessed the age-related changes in 24-h mean and hourly mean normal sinus R-R interval (mean NN), HRV (high frequency (HF) component, low frequency (LF) component and LF/HF) and the circadian rhythms. As a result, 24-h mean mean NN (0.976 +/- 0.115 vs 0.903 +/- 0.117 (s), p = 0.0019), LF/HF (1.681 +/- 0.731 vs 0.962 +/- 0.442, p = 0.0022), and LF (278.88 +/- 176.43 vs 179.19 +/- 132.33 (ms2), p = 0.0039) significantly decreased 15 years later, although 24-h mean HF (221.20+/-138.89 vs 310.78+/-296.73 (ms2), p = 0.1102) increased slightly. The hourly mean NN closely correlated with hourly HF and LF/HF throughout circadian rhythms both at first and second monitoring. In the morning hours, amplitude rates of all HRV indices increased significantly 15 years later. CONCLUSION: In elderly people, age-related changes in the 24-h mean heart rate (HR) were conversely dissociated from those of the 24-h mean HRV. However, the close correlation between hourly HR and HRV was preserved, even in very elderly patients. Additionally, the amplitude rates in HRV in the morning increased with age. These age-related changes of HR and HRV might be characteristic of elderly people.

Adolescent↗

Basic characteristics of chronic hypotension cases: a longitudinal follow-up study from 1958 through 1999.

Few epidemiological studies have been conducted on the prevalence, blood pressure trends by age, and basic characteristics of chronic hypotension. Among 13,370 subjects (5,094 men and 8,276 women) examined from 1958 to 1999 in Japan, 92 were identified as chronic hypotensives (11 men and 81 women) whose systolic blood pressure (SBP, mmHg) was lower than 100 mmHg for 8 or more years. Trends of SBP and body mass index (BMI, kg/m2) were determined over a 16-year period in this group of chronic hypotensives and 276 age- and sex-matched controls (33 men and 243 women); during this 16-year period, the chronic hypotensives and controls ranged in age from 19 to 75 years. BMI, heart rate (HR, bpm), body temperature (degrees C), Hb (g/dl), and creatinine (Cre, mg/dl) were compared between the chronic hypotensives and the controls at the last examination. The chronic hypotensives had a female preponderance (0.2% in men and 1.0% in women, p=0.001), and their SBP and BMI increased little with increasing age. BMI (20.2+/-3.4), BMI-adjusted SBP (101+/-19), HR (63+/-10), body temperature (36.7+/-0.3), Hb (12.5+/-1.1), and Cre (0.81+/-0.13) were lower in the chronic hypotensives than those (22.9+/-3.4, 126+/-20, 68+/-10, 36.8+/-0.3, 12.9+/-1.1, and 0.86+/-0.12, respectively) in controls (p<0.05). The present results clearly show that chronic hypotensives have a female preponderance and low BMI, HR, body temperature, Hb, and Cre in addition to low SBP that does not increase with age.

Age Factors↗

Longitudinal age-related changes in 24-hour total heart beats and premature beats and their relationship in healthy elderly subjects.

The aim of this study was to conduct a longitudinal follow-up on age-related changes in 24-hour total heart beats (THBs) and total premature beats and their correlations in healthy elderly subjects. In 15 healthy elderly subjects (mean age, 70.0 +/- 4.1, age range at 1st recording, 64 to 80 years, 10 females, 5 males), we conducted Holter monitoring twice at an interval of 15 years and analysed age-related changes in THBs, atrial premature beats (APBs), and ventricular premature beats (VPBs), as well as their correlations. The results indicated that THBs, APBs, and VPBs all significantly increased with age in the healthy elderly subjects at a mean age of 70.0 +/- 4.1 (THB: 91074.1 +/- 11515.3 versus 99457.5 +/- 12131.0; P = 0.0004, APB:119.2 +/- 97.8 versus 884.4 +/- 1193.8; P = 0.0008, VPB: 15.2 +/- 53.6 versus 140.7 +/- 228.9; P = 0.0328). Moreover, we divided the subjects into increase and nonincrease groups based on the age-related changes in APB and VPB for 15 years ([n]; Inc-APB: Noninc-APB = 6 : 9, Inc-VPB: Noninc-VPB = 5 : 10). In the increase groups, premature beats tended to increase in proportion to changes in THBs with age (APB: Y = 207.488 + 0.136 X, r = 0.848, P = 0.0303; VPB: Y = -27.594 + 0.028 X, r = 0.727, P = 0.1921). In conclusion, this 15-year follow-up of Holter recordings in healthy elderly subjects revealed that THBs, APBs, and VPBs increased with age, and that the increases in premature beats, especially APBs, were in proportion to those in THBs.

Adolescent↗

[Plasma B-type natriuretic peptide (BNP) measuring].

Brain or B-type natriuretic peptide (BNP) is a potent natriuretic, diuretic and vasorelaxant peptide and inhibits sympathetic tone, the renin-angiotensin-aldosterone system, and synthesis of vasoconstrictive molecules. The major source of plasma BNP is the cardiac ventricles. Elevated plasma BNP concentrations correlate with increased left ventricular (LV) filling pressure. Therefore BNP is a useful biomarkers as a screening tool for LV dysfunction. It also is a strong diagnostic indicator for both systolic and diastolic LV dysfunction. Measurement of plasma BNP is proved to be not only an efficient but also a cost effective screening tool for identifying patients with acute dyspnea of unknown etiology.

Biomarkers↗