Biomedical subjects

Minoru Yoshiyama

Publications and source records attributed to Minoru Yoshiyama.

At least 73 records · Page 4Linked to original sources

PubMed2004

Noninvasive coronary flow velocity reserve measurement in the posterior descending coronary artery for detecting coronary stenosis in the right coronary artery using contrast-enhanced transthoracic Doppler echocardiography.

BACKGROUND: Coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) has been found to be useful for assessing left anterior descending coronary artery (LAD) stenosis. However, this method has been restricted only for the LAD. The purpose of this study was to detect severe right coronary artery (RCA) stenosis by CFVR measurement using contrast-enhanced TTDE. METHODS: In 60 consecutive patients with angina pectoris (mean (SD) age: 60 (11), 18 women), coronary flow velocities in the RCA were recorded in the postero-descending coronary artery by contrast-enhanced TTDE at rest and during hyperemia induced by intravenous infusion of adenosine triphosphate (140 mcg/ml/kg). CFVR was calculated as the ratio of hyperemic to basal peak and mean diastolic flow velocity. CFVR measurements by TTDE were compared with the results of coronary angiography performed within 1 week. RESULTS: Coronary flow velocity was successfully recorded in 49 (82%) of the 60 patients with contrast agent. CFVR (mean (SD)) was 1.4 (0.4) in patients with, and 2.6 (0.6) in patients without significant stenosis in the RCA (%diameter stenosis > 75%, P < 0.001). Using the cutoff value 2.0 for CFVR in the RCA, its sensitivity and specificity in detecting significant stenosis in the RCA were 88% and 91%, respectively. CONCLUSION: CFVR measurement in the postero-descending coronary artery by contrast enhanced TTDE is a new, noninvasive method to detect significant stenosis in the RCA.

Adenosine Triphosphate↗

PubMed2004

Long-term beneficial effect of infarct-related artery patency in acute anterior myocardial infarction in patients with poor myocardial viability in the region-at-risk.

BACKGROUND: Several studies have demonstrated the benefit of the patency of infarct-related artery (IRA) in acute myocardial infarction (AMI). However those studies have not been concerned with myocardial viability in the region-at-risk. In the present study the effect of the patency of IRA was investigated in the setting of anterior AMI with poor viable myocardium in the risk region. METHODS AND RESULTS: From 1993 to 1996 patients with a first time anterior AMI and poor viable myocardium in the region-at-risk at 1 month after onset were identified and enrolled. Patients with a totally occluded IRA were included in the Non-Open group (n=44), and patients with a reperfused IRA were included in the Open group (n=49). At 5 years after onset, left ventricular function was better preserved in the Open group than in the Non-Open group (p<0.05). Kaplan-Meier survival curves for cardiac mortality and event-free survival curves revealed poor prognoses in the Non-Open group over a 5-year period (p<0.05, respectively). The advantages of a patent IRA were further seen in health-related quality-of-life outcomes (p<0.05). CONCLUSIONS: Even in patients with poor myocardial viability after an anterior AMI, the patency of the IRA is strongly associated with improved long-term survival, independent of residual myocardium viability.

Aged↗

PubMed2004

Convalescent stage coronary flow reserve and late myocardial morphologic outcomes in patients with first anterior acute myocardial infarction.

BACKGROUND: Microvascular damage immediately after reperfusion therapy is an independent predictor of left ventricular function in patients with acute myocardial infarction (AMI). However, its recovery may vary among individuals and the relationship between convalescent stage microvasculature and late myocardial morphologic change is unclear. METHODS AND RESULTS: Patients treated with coronary angioplasty within 12 h of their first anterior AMI were enrolled in this study. Coronary flow reserve (CFR) was measured 3 weeks post AMI, in both branches of the left coronary artery: culprit (left anterior descending artery: LAD) and non-culprit (left circumflex artery: LCX). Left ventriculography was performed at 3 weeks and 6 months post AMI and compared. Seventeen patients showed abnormal CFR in the LAD (Group 1: CFR<2), whereas 20 patients showed normal CFR (Group 2: CFR >/=2). Percent changes of end-diastolic volume tended to be higher in Group 1 than in Group 2 (11.8+/-21.6% vs -1.3+/-14.4%, p=0.056), and %changes of end-systolic volume was significantly smaller in Group 2 (11.8+/-22.1% vs -8.7+/-25.1%, p<0.05). A statistically significant correlation was found between absolute and relative CFR in the LAD and %change of end-systolic volume (r=-0.58: p<0.001, and r=0.40: p<0.05, respectively). CONCLUSIONS: Microvascular function in the convalescent stage may be related to these favorable changes.

Aged↗

PubMed2004

Effects of aldosterone receptor antagonist and angiotensin II type I receptor blocker on cardiac transcriptional factors and mRNA expression in rats with myocardial infarction.

BACKGROUND: Because the effects of an aldosterone receptor antagonist on transcriptional factors and mRNA expression have not been fully examined in myocardial infarction (MI), the present study examined the effects of spironolactone (SPIRO) and candesartan cilexitil (CAN) on activation of activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB) and mRNA expression in the non-ischemic myocardium after MI. METHODS AND RESULTS: MI was induced by ligation of the coronary artery in Wistar rats, which were separated into (1) vehicle-treated group, (2) CAN-treated group (10 mg/kg per day), (3) SPIRO-treated group (100 mg/kg per day) and (4) CAN + SPIRO-treated group. The activity of both AP-1 and NF-kappaB was significantly increased at 4 weeks after MI. CAN or SPIRO significantly prevented the cardiac remodeling and activity of AP-1 and NF-kappaB. Furthermore, CAN + SPIRO prevented the cardiac remodeling and activation of AP-1 and NF-kappaB, compared with CAN or SPIRO alone. Myocardial atrial natriuretic peptide, brain natriuretic peptide, collagen I and III mRNAs were enhanced by MI, and CAN or SPIRO alone significantly reduced the mRNAs. CAN + SPIRO significantly prevented these mRNAs, compared with CAN or SPIRO alone. CONCLUSIONS: Both aldosterone and angiotensin II are involved in the myocardial transcriptional activation of AP-1, NF-kappaB and the cardiac remodeling-related mRNAs. The combination of CAN and SPIRO may be a potent therapeutic strategy for preventing cardiac remodeling after MI.

Animals↗

PubMed2004

Effects of cellular cardiomyoplasty on ventricular remodeling assessed by Doppler echocardiography and topographic immunohistochemistry.

BACKGROUND: Myocardial infarction (MI) promotes deleterious remodeling of the myocardium, resulting in ventricular dilation and pump dysfunction. Supplementing infarcted myocardium with neonatal myocyte would attenuate deleterious remodeling and so the present study used Doppler echocardiography and histology to analyze the cardiac function and histological regeneration of the damaged myocardium after cellular cardiomyoplasty. METHODS AND RESULTS: Experimental MI was induced by 24-h coronary ligation followed by reperfusion in adult male Lewis rats and neonatal myocytes were injected directly into the infarct and peri-infarct regions. Three groups of animals were studied at 4 weeks after cellular cardiomyoplasty: noninfarcted control (control), MI plus sham injection (MI), and MI plus cell injection (MI + cell). Ventricular remodeling and cardiac performance were assessed by Doppler echocardiography or contrast echocardiography. At 4 weeks after cellular cardiomyoplasty, MI + cell hearts exhibited attenuation of global ventricular dilation and cardiac function compared with MI hearts not receiving cellular cardiomyoplasty. Immunohistochemically, connexin-43-positive small cells were observed in the vicinity of the infarction in MI + cell heart. By electron microscopy, these cells contained myofilaments with Z-bands and poorly developed intercalated disks, suggesting neonatal myocardial cells. Furthermore, the myocardial cells were often making close contact with interstitial cells. CONCLUSIONS: Implanted neonatal myocytes form viable grafts after MI, resulting in attenuated ventricular dilation and enhanced contractile function. Echocardiography, electron microscopy, and immunohistochemistry are useful methods for assessing the functional and histological regeneration of the damaged myocardium.

Actin Cytoskeleton↗

PubMed2004

Detecting viable myocardium and predicting functional improvement: comparisons of positron emission tomography, rest-redistribution thallium-201 single-photon emission computed tomography (SPECT), exercise thallium-201 reinjection SPECT, I-123 BMIPP SPECT and dobutamine stress echocardiography.

BACKGROUND: Low-dose dobutamine stress echocardiography (LDDE) has become a useful and safe method for identifying hibernating or stunned myocardium and for predicting improvement in wall motion after coronary revascularization. METHODS AND RESULTS: In the present study, fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), rest-redistribution thallium-201 ((201)Tl) single-photon emission computed tomography (RR-Tl SPECT), (123)I-15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid (BMIPP) and LDDE were performed in 30 patients with acute myocardial infarction (AMI) at 10+/-3 days after the onset of AMI. Also, exercise (201)Tl reinjection SPECT (RI-Tl SPECT) was performed at 14+/-2 days. Follow-up echocardiography was performed 5+/-3 months later in all patients after interventional therapy for the assessment of functional recovery. Of the 390 segments analyzed by echocardiography, 110 (28%) had abnormal wall motion. There were no significant differences between RR-Tl SPECT and LDDE in sensitivity, specificity, positive predictive value and negative predictive value using the chi(2)-test; however, in akinetic segments, there was a significant difference in sensitivity. Among FDG-PET, RI-Tl SPECT, BMIPP and LDDE, there were significant differences in 3 variables. In akinetic segments, LDDE is superior to RR-Tl SPECT in sensitivity and to FDG-PET in specificity. In hypokinetic segments, LDDE is superior to RI-Tl SPECT and BMIPP in sensitivity, and to FDG-PET and BMIPP in specificity. CONCLUSIONS: LDDE could detect functional recovery of viable myocardium in the early period of AMI and can be performed easily and safely.

Aged↗

PubMed2004

Additive improvement of left ventricular remodeling by aldosterone receptor blockade with eplerenone and angiotensin II type 1 receptor antagonist in rats with myocardial infarction.

We investigated the effects of the aldosterone blocker eplerenone alone and in combination with angiotensin II type 1 receptor antagonist on ventricular remodeling in rats with left ventricular (LV) dysfunction after extensive myocardial infarction (MI). Adding an aldosterone antagonist to an ACE inhibitor reduces mortality and morbidity in heart failure. Starting 1 day after MI, rats were treated with placebo, eplerenone (100 mg/kg/day), the angiotensin type 1 receptor antagonist candesartan (1 mg/kg/day), or a combination of both for nine weeks. Both monotherapies attenuated the rise in LV end-diastolic dimension (LVDd) and LV end-diastolic volume (LVEDV) compared with placebo, whereas combined treatment further attenuated LVDd and LVEDV and significantly improved LV function. Increased collagen type I and III gene expressions in the noninfarcted LV myocardium from MI placebo rats was attenuated by candesartan, but almost completely prevented by eplerenone and eplerenone/candesartan. The addition of eplerenone to candesartan prevented the increases in LV gene expression of ANP and BNP more effectively than either monotherapy. The aldosterone blocker eplerenone improved LV remodeling in rats with LV dysfunction after extensive MI. Combination therapy with an candesartan substantially potentiates this effect by a complementary prevention of LV fibrosis, cardiac hypertrophy, and molecular alterations.

Angiotensin Receptor Antagonists↗

PubMed2004

Cardioprotective effect of SEA0400, a selective inhibitor of the Na(+)/Ca(2+) exchanger, on myocardial ischemia-reperfusion injury in rats.

In this study, we investigated whether the Na(+)/Ca(2+) exchanger (NCX) inhibitor SEA0400 (2-[4-[(2,5-difluorophenyl)methoxy]phenoxy-5-ethoxyaniline) might have a protective effect against myocardial ischemia-reperfusion injury in rats. In particular, we focused on cardiac function using Doppler echocardiography and cardiac gene expression. We intravenously administered either SEA0400 and delivery vehicle or only the vehicle (as a control) to Wistar rats 5 min before ischemia was induced. Reperfusion was performed after 30 min of ischemia. At 1 week after ischemia-reperfusion injury, we assessed hemodynamics by inserting a polyethylene-tubing catheter, cardiac function by Doppler echocardiography, and myocardial mRNA expression was determined by Northern blot analysis. Left ventricular (LV) end-diastolic dimensions (LVDd) and LV end-diastolic volume (LVEDV) were significantly increased in the ischemia-reperfusion rat model group compared to the control group. The SEA0400-treated group had a significantly attenuated LVDd (P<0.05) and LVEDV (P<0.01) increase, compared to the vehicle-treated group. A decrease in the LV ejection fraction (P<0.05) was significantly prevented in the SEA0400-treated group compared to the vehicle-treated group. Moreover, mRNA expression of plasminogen activator inhibitor-1 in the non-infarcted LV of the SEA0400-treated group was significantly lower than in the vehicle-treated group (P<0.05). This study demonstrates that the NCX is an important mechanism for cell death in myocardial ischemia and reperfusion in rats. SEA0400 may prove to be a promising new drug in the clinical treatment of myocardial ischemia and reperfusion.

Aniline Compounds↗

PubMed2004

Additive beneficial effects of the combination of a calcium channel blocker and an angiotensin blocker on a hypertensive rat-heart failure model.

The present study was undertaken to examine the effects of a calcium channel blocker, azelnidipine (1 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, temocapril (10 mg/kg/day), an angiotensin II type 1 (AT1) receptor blocker (ARB), olmesartan (5 mg/kg/day), and their combination on Dahl salt-sensitive rats (DS rats) developing heart failure with preserved systolic function. DS rats were fed a high-salt diet (8% NaCl) from 7 weeks of age and progressively developed hypertension. Although monotherapy with azelnidipine lowered the blood pressure of DS rats to a greater extent than monotherapy with temocapril or olmesartan, the three drugs had similar effects on cardiac hypertrophy, cardiac fibrosis, the expressions of brain natriuretic peptide, transforming growth factor-beta1, collagen I, collagen III and monocyte chemoattractant protein-1 mRNA (as estimated by Northern blot analysis), and cardiac diastolic dysfunction (as estimated by echocardiography). These results show that ACE and AT1 receptor, as well as hypertension, are involved in the development of heart failure with preserved systolic function in DS rats. The combination of azelnidipine with olmesartan or temocapril produced no additive hypotensive effect in DS rats and no additive effect on cardiac hypertrophy or gene expressions. However, the combination therapy prolonged the survival rate of DS rats more than azelnidipine (p <0.01) or temocapril alone (p <0.05), and this additive beneficial effect by the combination therapy was associated with a greater reduction of cardiac fibrosis, urinary albumin excretion and serum creatinine. Our results thus showed that the combination of a calcium channel blocker with an ARB or an ACE inhibitor had additive preventive effects on a rat model of hypertensive heart failure with preserved systolic function. Thus, combination therapy with these agents seems to be a useful therapeutic strategy for the prevention of hypertensive heart failure.

Albuminuria↗

PubMed2004

New noninvasive diagnosis of myocardial ischemia of the left circumflex coronary artery using coronary flow reserve measurement by transthoracic Doppler echocardiography: comparison with thallium-201 single photon emission computed tomography.

OBJECTIVES: The usefulness of coronary flow reserve measurement in the left circumflex coronary artery by transthoracic Doppler echocardiography to detect myocardial ischemia was compared with exercise thallium-201 single photon emission computed tomography (SPECT). METHODS: Transthoracic Doppler echocardiography was performed in 110 patients with suspected coronary artery disease. Color Doppler signals of the left circumflex coronary artery flow in the apical four-chamber view were identified, and the velocities at rest and during hyperemia recorded for calculation of coronary flow reserve by the pulsed Doppler method. All patients underwent SPECT within 1 week of the transthoracic Doppler echocardiographic study. RESULTS: Coronary flow reserve in the left circumflex coronary artery was measured in 79 (72%) of 110 patients. SPECT revealed reversible perfusion defect in the left circumflex coronary artery territories in 12 of 69 patients excluding those with multivessel disease. Coronary flow reserve < 2.0 had a sensitivity of 92% and specificity of 96% for reversible perfusion defect detected by SPECT. CONCLUSIONS: Noninvasive coronary flow reserve measurement in the left circumflex coronary artery by transthoracic Doppler echocardiography can estimate myocardial ischemia in the left ventricular lateral regions.

Aged↗

PubMed2004

Antecedent hypertension interacts with adverse ventricular remodeling after myocardial infarction.

BACKGROUND: Ventricular remodeling is an independent predictor of left ventricular function in patients with myocardial infarction (MI). Accelerated ventricular remodeling is a probable contributor to the increased mortality observed after MI in hypertensive patients. The purpose of this study is to assess the relationship of antecedent hypertension to ventricular remodeling after MI. METHODS: Seventy-nine patients presenting with a first acute MI (AMI) who were treated and attained Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 with re-perfusion therapy within 12 hours of their symptom onset were enrolled in this study. All of them underwent left ventriculography (LVG) immediately after re-perfusion therapy and again at 6 months after the occurrence of MI. Patients were divided into two groups; hypertensive group and normotensive group. End-diastolic volume index (EDVI), end-systolic volume index (ESVI), and EF were compared between acute phase and 6 months after AMI in each group. RESULTS: The hypertensive group showed a significant increase in both EDVI and ESVI after 6 months, whereas the normotensive group did not. In addition, there was no change in EF in the hypertensive group, whereas EF increased significantly after 6 months in the normotensive group. As a result, percent change in ESVI and EF showed significantly differences between the hypertensive group and normotensive group, whereas percent change in EDVI showed no significant difference between the two groups. CONCLUSIONS: Antecedent hypertension interacts with ventricular remodeling after MI.

Aged↗

PubMed2004

Impact of HMG-CoA reductase inhibitors for non-treated coronary segments.

BACKGROUND: HMG-CoA reductase inhibitors (statin) have been reported to decrease coronary artery events in several angiographic studies. However, the mechanism by which statin achieve this is still unclear. The purpose of this study was to identify the effect of statin on coronary plaque using serial intravascular ultrasound analysis. METHODS AND RESULTS: In this study, 48 patients with 48 lesions were divided into the prescribed group (statin group, n = 22) or the non-prescribed group (control group, n = 26) after successful coronary artery stenting. IVUS images were obtained at consecutive 5 mm segments, 5 mm from the proximal stent edge, immediately after stenting and at 6 months follow up. External elastic membrane volume (EEMV), lumen volume (LV) and plaque volume (PV) were measured using Simpson's method. The control group revealed no significant serial change in EEMV, PV, and LV during 6 months. On the other hand, the statin group revealed significant reductions of PV (35.5 +/- 12.7 mm3 vs 30.9 +/- 15.6 mm3, p = 0.001), resulting in increase of LV (47.7 +/- 19.8 mm3 vs 52.5 +/- 22.2 mm3, p = 0.003) without EEMV change (82.8 +/- 21.8 mm3 vs 83.9 +/- 25.7 mm3, p = NS). Although percent EEMV and percent LV changes showed no differences between the two groups, a larger percent PV change was observed in the statin group compared to the control group (control; 5.8 +/- 20.3% vs statin; -20.4 +/- 21.8%, p = 0.02). CONCLUSION: The results of this study suggest that statin administration for 6 months reduces coronary plaque without positive vessel remodeling.

Aged↗

PubMed2004

The relationship between left ventricular geometric remodeling and cardiac function in essential hypertension.

BACKGROUND: Abnormal left ventricular (LV) diastolic relaxation is an early sign of hypertensive heart disease. Whether diastolic dysfunction differs between LV geometric patterns remains controversial. METHODS AND RESULTS: We examined 220 hypertensive patients by echocardiography to assess the relationship between diastolic function and LV geometric pattern. We identified four LV geometric patterns: normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Diastolic function was evaluated by the E/A ratio, E wave deceleration time (Dct), and isovolumic relaxation time (IRT). The E/A ratio was below one and Dct was prolonged in each group. The duration of IRT in the concentric and eccentric hypertrophy groups was significantly longer than that in normal geometry and concentric remodeling groups (p < 0.05). CONCLUSIONS: Hypertensive patients may be possible to have diastolic dysfunction, regardless of the differences in their structural geometry. The degree of impairment of cardiac diastolic function differed between hypertensive patients with different LV geometric patterns.

Aged↗

PubMed2004

The impact of IVUS guided bare metal stent implantation for non-small vessel.

UNLABELLED: Previous studies have shown larger target vessel or greater stent area contribute to reduced restenosis rate. Thus, intravascular ultrasound (IVUS)-guided bare metal stent (BMS) implantation for selected lesions might achieve drug-eluting stent-like outcomes. The aim was to examine the long-term outcomes of BMS using IVUS-guided optimization. METHODS: Consecutive 103 coronary artery lesions suitable for IVUS were enrolled. Using IVUS, final stent balloon size selected was 90 percent of media-to-media diameter at the lesion or distal reference. The balloon size was listed as follows: group A (3.0-3.5 mm, n = 15), group B (3.5-3.75 mm, n = 64), and group C (3.75-4.5 mm, n = 24). RESULTS: At post-intervention, average stent area increased by the balloon size (A: 7.2 +/- 1.4 mm2, B: 8.9 +/- 1.5 mm2, and C: 12.1 +/- 2.0 mm2, respectively p < 0.001). At 6 month follow up, the average lumen area increased by balloon size (A: 4.1 +/- 1.7 mm2, B: 5.7 +/- 1.2 mm2, and C: 8.1 +/- 2.0 mm2, respectively p < 0.001). Accordingly, group B and C revealed lower restenosis, compared to group A (A: 46.7%, B: 10.9%, C: 8.3%, A vs B: p = 0.001; C vs A: p = 0.015). Moreover, target lesion revascularization was less in group B and C than group A (A 26.6%, B 3.1%, C 0%, A vs B: p = 0.011; C vs A: p = 0.017). CONCLUSIONS: For non-small vessels, IVUS-guided BMS implantation showed less restenosis and target lesion revascularization compared to small vessels, mainly due to larger initial gain. These study results suggest that IVUS-guided optimal BMS implantation for selected lesions might result in favorable long-term outcomes similar to those seen using drug-eluting stents. For a decade, coronary stenting has become a standard therapy for coronary artery disease due to favorable long-term outcomes and simple treatment procedure. Furthermore, for the last two years, drug-eluting stents (DES), releasing antiproliferative agents from bare metal backbone, revealed the restenosis rates less than half of those seen using conventional bare metal stents (BMS). While target lesions especially suitable for DES continue to be identified, earlier BMS studies showed that larger target vessel or greater stent area contributed to less restenosis. Thus, optimal IVUS-guided BMS implantation for selected lesions might achieve DES-like long-term outcomes. This study was designed to examine the long-term outcomes of BMS with intravascular ultrasound (IVUS)-guided optimization, using coronary angiography and IVUS data.

Aged↗

PubMed2003

Involvement of apoptosis signal-regulating kinase-1 on angiotensin II-induced monocyte chemoattractant protein-1 expression.

OBJECTIVE: Monocyte chemoattractant protein 1 (MCP-1) could contribute to enhanced leukocyte recruitment and activation resulting in chronic tissue damage. However, little is known about the molecular mechanisms of cardiac MCP-1 expression. To elucidate these molecular mechanisms, angiotensin II-induced expression of MCP-1 was examined in cultured rat neonatal ventricular cardiomyocytes and fibroblasts by adenovirus gene transfer. METHODS AND RESULTS: MCP-1 mRNA increased 3.6-fold in cardiac fibroblasts at 3 hours after 100 nmol/L angiotensin-II stimulation (P<0.01), whereas MCP-1 mRNA in cardiomyocytes was unchanged. Angiotensin II significantly enhanced JNK, p38MAPK, and nuclear factor-kappaB (NF-kappaB) activities of cardiac fibroblasts. Wild-type ASK-1 increased MCP-1 expression of cardiac fibroblasts, whereas dominant negative mutant of ASK-1 (DN-ASK), dominant negative mutant of p38MAPK (DN-p38MAPK), and pyrrolidine dithiocarbamate significantly inhibited such expression. The increased MCP-1 mRNA expression in wild-type ASK-1 transfected fibroblasts was inhibited by cotransfection with adenovirus expressing DN-p38MAPK. On the contrary, the decreased MCP-1 mRNA expression in DN-ASK transfected cells was increased by cotransfection with adenovirus expressing constitutively active MKK6. CONCLUSIONS: Angiotensin II induced MCP-1 gene expression in cardiac fibroblasts. The angiotensin II-induced activation of ASK-1 followed by p38MAPK and NF-kappaB signaling in cardiac fibroblasts is partially involved in myocardial MCP-1 expression.

Adenoviridae↗

PubMed2003

Cut-off value of coronary flow velocity reserve by transthoracic Doppler echocardiography for diagnosis of significant left anterior descending artery stenosis in patients with coronary risk factors.

The purpose of this study was to evaluate the adequate cut-off value of coronary flow velocity reserve (CFVR) with transthoracic Doppler echocardiography for diagnoses of significant left anterior descending (LAD) artery stenosis in a large study population with various coronary risk factors. CFVR, which has been used for evaluation of significant coronary artery stenosis, can be reduced despite angiographically normal coronary arteries in patients with various coronary risk factors. However, the adequate cut-off value of CFVR for diagnosing significant LAD stenosis has not been fully established in patients with coronary risk factors. We examined 138 consecutive patients who underwent coronary angiography. Clinical histories of coronary risk factors were determined from interviews or medical records. CFVR assessment in the LAD artery by transthoracic Doppler echocardiography was performed in all patients. Of the 138 patients, 30 had significant stenosis, and the remainder had no stenotic lesions in the LAD artery. Receiver-operating characteristic curves for detection of significant LAD stenosis showed that a cut-off value of <2.0 was extremely precise. A cut-off value <2.0 of CFVR had a sensitivity of 90%, a specificity of 93%, a positive predictive value of 77%, and a negative predictive value of 97% for the presence of significant LAD stenosis. A cut-off value <2.0 of CFVR by transthoracic Doppler echocardiography was adequate for the diagnosis of significant LAD stenosis in a population that included patients with coronary risk factors.

Blood Flow Velocity↗

PubMed2003

Activation of apoptosis signal-regulating kinase 1 in injured artery and its critical role in neointimal hyperplasia.

BACKGROUND: Apoptosis signal-regulating kinase 1 (ASK1), recently identified as one of the mitogen-activated protein kinase kinase kinases, is activated by various extracellular stimuli and involved in a variety of cellular function. Therefore, we first examined the role of ASK1 in vascular remodeling. METHODS AND RESULTS: We used rat balloon injury model and cultured vascular smooth muscle cells (VSMCs). Arterial ASK1 activity was rapidly and dramatically increased after balloon injury. To specifically inhibit endogenous ASK1 activation, dominant-negative mutant of ASK1 (DN-ASK1) was transfected into rat carotid artery before balloon injury. Gene transfer of DN-ASK1 significantly prevented neointimal formation at 14 days after injury. Bromodeoxyuridine labeling index at 7 days after injury showed that DN-ASK1 remarkably suppressed VSMC proliferation in both the intima and the media. We also examined the role of ASK1 in cultured rat VSMCs. Infection with DN-ASK1 significantly attenuated serum-induced VSMC proliferation and migration. We also compared neointimal formation after cuff placement around the femoral artery between mice deficient in ASK1 (ASK1-/- mice) and wild-type (WT) mice. Neointimal formation at 28 days after cuff injury in ASK1-/- mice was significantly attenuated compared with WT mice. Furthermore, we compared the proliferation and migration of VSMCs isolated from ASK1-/- mice with WT mice. Both proliferation and migration of VSMCs from ASK1-/- mice were significantly attenuated compared with VSMCs from WT mice. CONCLUSIONS: ASK1 activation plays the key role in vascular intimal hyperplasia. ASK1 may provide the basis for the development of new therapeutic strategy for vascular diseases.

Adenoviridae↗

PubMed2003

Apoptosis signal-regulating kinase 1 plays a pivotal role in angiotensin II-induced cardiac hypertrophy and remodeling.

Multiple lines of evidence establish that angiotensin II (Ang II) induces not only hypertension but also directly contributes to cardiac diseases. Apoptosis signal-regulating kinase 1 (ASK1), one of mitogen-activated protein kinase kinase kinases, plays a key role in stress-induced cellular responses. However, nothing is known about the role of ASK1 in cardiac hypertrophy and remodeling in vivo. In this study, by using mice deficient in ASK1 (ASK1-/- mice), we investigated the role of ASK1 in cardiac hypertrophy and remodeling induced by Ang II. Left ventricular (LV) ASK1 was activated by Ang II infusion in wild-type mice, which was mediated by angiotensin II type 1 receptor and superoxide. Although Ang II-induced hypertensive effect was comparable to wild-type and ASK1-/- mice, LV ASK1 activation by Ang II was not detectable in ASK1-/- mice, and p38 and c-Jun N-terminal kinase (JNK) activation was lesser in ASK-/- mice than in wild-type mice. Elevation of blood pressure by continuous Ang II infusion was comparable between ASK1-/- and wild-type mice. However, Ang II-induced cardiac hypertrophy and remodeling, including cardiomyocyte hypertrophy, cardiac hypertrophy-related mRNA upregulation, cardiomyocyte apoptosis, interstitial fibrosis, coronary arterial remodeling, and collagen gene upregulation, was significantly attenuated in ASK1-/- mice compared with wild-type mice. These results provided the first in vivo evidence that ASK1 is the critical signaling molecule for Ang II-induced cardiac hypertrophy and remodeling. Thus, ASK1 is proposed to be a potential therapeutic target for cardiac diseases.

Angiotensin II↗