[Therapeutic guidelines for heart failure].
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Chronic Disease↗
Biomedical subjects
Hiroyuki Daida
Publications and source records attributed to Hiroyuki Daida.
Pravastatin may prevent disease progression in normocholesterolemic people with coronary artery disease. Commentary.
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Comment↗
Adeno-associated virus 2-mediated intratumoral prostate cancer gene therapy: long-term maspin expression efficiently suppresses tumor growth.
Maspin is a member of the serine protease inhibitors and the maspin gene, a tumor suppressor gene, is down-regulated in a large fraction of prostate cancers. We evaluated the use of adeno-associated virus (AAV, serotype 2) vector encoding maspin as a means for in vivo gene therapy for human prostate cancer. TUNEL assay of subcutaneously formed LNCaP or DU145 tumors in nude mice showed that intratumoral AAV-mediated maspin expression significantly upregulated the number of apoptotic cells compared with AAV-LacZ treatment. Immunofluorescence double staining for maspin protein and apoptosis in LNCaP tumors showed that the percentage of apoptotic cells in AAV-maspin-mediated maspin-expressing cells was significantly high compared with that in AAV-GFP-mediated GFP-expressing cells. Moreover, significantly fewer CD31-positive microvessels were observed in AAV-maspin-treated tumors compared with the control tumors. These therapeutic responses were highly correlated to persistent maspin expression in tumors, confirmed by Western blot analysis until at least day 56 after treatment. Finally, intratumoral delivery of AAV-maspin significantly suppressed growth of LNCaP and DU145 tumors and improved survival of mice. We conclude that AAV-mediated prolonged maspin expression efficiently suppresses human prostate tumor growth in vivo by apoptosis induction and inhibition of angiogenesis.
Animals↗
Hepatocyte growth factor receptor is a coreceptor for adeno-associated virus type 2 infection.
After the first attachment of virus to the cell surface through a primary receptor, efficient entry of virus requires the presence of a coreceptor. For adeno-associated virus type 2 (AAV2) infection, heparan sulfate proteoglycan is supposed as the primary receptor, and alphavbeta5 integrin and FGFR1 are reported to act as coreceptors. In this study, we were able to demonstrate that hepatocyte growth factor receptor, c-Met, is also a coreceptor for AAV2 infection. AAV2-mediated transgene analyses revealed that c-Met expression significantly up-regulated transgene expression without increasing AAV2 cell binding. Moreover, a viral overlay assay elucidated the physical interaction between AAV2 and the beta subunit of c-Met. These data suggest that c-Met plays the role of coreceptor for AAV2 infection by facilitating AAV2 internalization into the cytoplasm.
3T3 Cells↗
Conversion and maintenance of sinus rhythm by bepridil in patients with persistent atrial fibrillation.
BACKGROUND: Bepridil has multiple ion-channel blocking effects similar to amiodarone and is expected to have anti-arrhythmic effects that are useful for the management of atrial fibrillation (AF). The aim of this study was to clarify the conversion of persistent AF and maintenance of sinus rhythm (SR) by oral bepridil. METHODS AND RESULTS: Oral bepridil was administered to 112 patients (83 males, 29 females; age: 59.0+/-10.8 years) with persistent AF lasting an average of 5 months. The conversion effects and maintenance of SR after pharmacological or direct current (DC) cardioversion, as well as the incidence of adverse complications, were evaluated. In 65 of 112 (58%) patients, SR was restored within 6 months (average: 2.1 months) following bepridil administration. DC cardioversion was carried out for 21 of the remaining 47 patients with unsuccessful pharmacological conversion, and all had restoration of SR. Eventually, of the 86 patients in total who were restored to SR by either bepridil or DC cardioversion, 70 (81%) patients maintained SR after a mean follow-up of 18 months. No serious adverse complications were observed, except for marked QT prolongation in 2 cases. CONCLUSION: Bepridil showed favorable conversion effects in patients with persistent AF and was highly effective for maintaining SR after pharmacological or electrical cardioversion. However, careful follow-up is necessary for the prevention of torsade de pointes caused by QT prolongation.
Adult↗
Effect of pravastatin on progression of coronary atherosclerosis in patients after coronary artery bypass surgery.
BACKGROUND: Although the anti-atherosclerotic effects of HMG-CoA reductase inhibitors are well known, their specific effect on saphenous vein grafts after coronary artery bypass graft (CABG) operation is not well documented and has not been studied in Japan, so the aim of the present prospective randomized controlled study involving 27 Japanese institutions was to investigate the effects of pravastatin on the progression of atherosclerosis in such grafts and native coronary arteries after CABG. METHODS AND RESULTS: A total of 303 patients who had undergone CABG were randomly assigned to either the pravastatin group (n =168) or the control group (n = 167). Paired coronary angiograms were obtained at baseline and at the end of 5-year follow-up in 182 (60%) patients. The low-density lipoprotein cholesterol concentration significantly decreased in the pravastatin group from 141.4 mg/dl to 113.7 mg/dl (-19.6%), compared with 141.1 mg/dl to 133.7 mg/dl (-5.2%) in the control group (p < 0.001). Although there was no significant difference in the quantitative coronary angiography measurements between the 2 groups, the global change score indicated a significant pravastatin-mediated reduction in plaque progression (p < 0.01). CONCLUSIONS: Pravastatin can potentially reduce atherosclerotic progression in both the bypass graft and native coronary arteries of patients after CABG.
Aged↗
Sinus node dysfunction concomitant with Brugada syndrome.
BACKGROUND: A genetic correlation between Brugada syndrome (BS) and sinus node dysfunction (SND) has been proposed, although the clinical and electrophysiologic characteristics of this concomitant condition are unknown. METHODS AND RESULTS: The study comprised 5 patients with symptomatic BS (4 with spontaneous episodes of ventricular fibrillation (VF) and 1 with syncope) of whom 3 had a documented sinus pause > 3 s (a 42- and 62-year-old man, and a 49-year-old woman). Only 1 of them had a family history of sudden death; 2 of them had also had an episode of atrial fibrillation or flutter. Electrophysiologic study demonstrated prolonged sinus node recovery time in 2 patients (2.6 s and > 5 s), in whom a cardiac pacemaker had been implanted before the diagnosis of BS was made after episodes of VF. Finally, all 3 patients received an implantable cardioverter defibrillator, including 2 upgrades from pacemaker. CONCLUSIONS: SND is not a rare concomitant disorder in BS and there is a possible genetic connection.
Adult↗
A Japanese case of familial cardiac myxoma associated with a mutation of the PRKAR1alpha gene.
Familial cardiac myxoma is inherited as an autosomal dominant syndrome. Here, we report a Japanese case of familial cardiac myxoma identified as a genetic abnormality. The mother experienced multiple recurrence of tumors in the left atrium and left ventricle 40 months after surgical resection of a left atrial myxoma. All recurrent tumors were successfully resected. Her daughter also had a solitary myxoma in the left atrium, but she had no recurrence after the operation. Both patients had lentigines in their face but no endocrine abnormality. Molecular genetic analysis demonstrated involvement of a mutation in the PRKAR1alpha gene.
Adolescent↗
Ventricular fibrillation refractory to ICD therapy.
A 14-year-old boy was admitted for the evaluation of recurrent syncope. His ECG on admission revealed a sinus rhythm with an undetermined QRS axis, T wave inversion at leads V3, V4 and abnormal q at leads I, aVL, V5 and V6. However, no underlying disease could be detected by any morphological examination. Programmed ventricular stimulation also induced no ventricular tachycardia or fibrillation (VF). Only signal-averaged ECG showed ventricular late potential and the cause of syncope was not clarified. As his brother with a similar ECG had died suddenly, he was prophylactically treated with an ICD. However, 14 months later he died suddenly after playing a video game. The ICD recorded VF, which was not converted despite 6 cardioversion attempts by the ICD. Progression of myocardial damages and/or elevation of defibrillation threshold may have been the cause of unsuccessful cardioversion.
Adolescent↗
Severe infundibular pulmonary stenosis and coronary artery stenosis with ventricular tachycardia 24 years after mediastinal irradiation.
A 28-year-old man developed severe infundibular pulmonary stenosis (PS), coronary artery stenosis with sustained ventricular tachycardia (VT) 24 years after mediastinal irradiation (total amount of 40 Gray) for non-Hodgkin's lymphoma. Repair of right ventricular outflow tract and coronary artery bypass graft procedure were performed. Infundibular PS was successfully relieved after operation and VT was also controlled by medication. Mediastinal irradiation often causes various cardiac complications after a latent period. Therefore, continuous careful observation is mandatory in patients with the history of mediastinal irradiation.
Adult↗
Some unanswered questions in re-stenosis prevention research.
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Biomedical Research↗
[Treatment for coronary artery disease patients with impaired glucose tolerance].
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Acarbose↗
[Health-related quality of life in Japanese patients with ischemic heart disease: a multicenter cooperative investigation assessed using SF-36].
OBJECTIVES: To investigate the quality of life (QOL) of Japanese patients with ischemic heart disease. METHODS: The QOL data of 753 patients with chronic and stable ischemic heart disease was assessed using SF-36 Japanese version 1.2 and compared with Japanese national norms. Physical (PCS) and Mental Component Summary (MCS) scores were calculated to examine the correlation with patient background. Patients were also asked about subjective symptoms during the QOL investigation. RESULTS: Mean age was 63.6 +/- 7.5 years old and the male/female ratio was 85.7/14.3. About one third (30.7%) of the patients were symptomatic and about half (52.6%) had a history of myocardial infarction. Compared to Japanese national norms, physical functioning, role-physical, social functioning, general health and role-emotional were lower, and body pain, vitality and mental health were higher. PCS was significantly lower and MCS was significantly higher in aged patients than in younger patients (p < 0.0001, p < 0.0001). PCS and MCS were significantly lower in the symptom (+) group than in the symptom (-) group (p = 0.0009, p < 0.0001). PCS decreased as the number of anti-angina medications for the patients increased (p = 0.0002). PCS was significantly lower and MCS was significantly higher in the beta blocker (+) group than in the beta blocker (-) group (p < 0.0001, p < 0.03). Multivariate logistic regression analysis showed that age ( > or = 63 years old), symptom (+), duration of disease (> or = 3 years) and beta blocker (+) influenced the QOL. CONCLUSIONS: The QOL level of patients with ischemic heart disease was found to depend on the clinical condition and treatment, so the optimal treatment for ischemic heart disease must be established to improve QOL.
Adrenergic beta-Antagonists↗
Dynamin-2 regulates oxidized low-density lipoprotein-induced apoptosis of vascular smooth muscle cell.
BACKGROUND: On exposure to oxidized low-density lipoprotein (oxLDL), vascular cells generally undergo apoptosis, which is one of the major pathogenic factors of atherosclerosis. In this study, we examined the role of dynamin (a crucial GTPase protein in endocytosis) in oxLDL-induced apoptosis of vascular smooth muscle cells (VSMC). METHODS AND RESULTS: After oxLDL stimulation, dynamin-2 colocalized with LOX-1 around the cell surface, as well as oxLDL in the cytoplasm, suggesting that dynamin-2 was involved in scavenger receptor-mediated oxLDL endocytosis. Downregulation of dynamin-2 induced by dynamin-2 dominant negative plasmid (K44A) resulted in a decrease of oxLDL uptake and thereby in a reduction of apoptosis. These data demonstrated that dynamin-2 was involved in oxLDL-induced apoptosis via the oxLDL endocytotic pathway. On the other hand, dynamin-2 wild-type plasmid transfection promoted oxLDL-induced apoptosis without increasing oxLDL uptake. Interestingly, the p53 inhibitor pifithrin-alpha (PFT) significantly reduced apoptosis promoted by wild-type dynamin-2 (78% reduction compared with the PFT[-] condition). These results indicated that dynamin-2 enhanced oxLDL-induced apoptosis of VSMC by participating in the p53 pathway, probably as a signal transducer. Moreover, we demonstrated that, in advanced plaques of apolipoprotein E-/- mice, dynamin-2 expression was often enhanced in apoptotic VSMC, suggesting that dynamin-2 might participate in apoptosis of VSMC even in vivo. CONCLUSIONS: Our data demonstrated that dynamin-2 at least partially regulated oxLDL-induced apoptosis of VSMC by participating in 2 independent pathways: the oxLDL endocytotic pathway and the p53 pathway. These findings suggest that dynamin-2 may serve as a new research or therapeutic target in vascular disease.
Animals↗
Circulating malondialdehyde-modified LDL and atherogenic lipoprotein profiles measured by nuclear magnetic resonance spectroscopy in patients with coronary artery disease.
OBJECTIVE: Recent studies have suggested that circulating malondialdehyde-modified low-density lipoprotein (MDA-LDL) is a useful marker for the identification of patients with coronary artery disease (CAD). However, the role of MDA-LDL in atherogenic mechanisms has not yet been fully determined. METHOD AND RESULTS: We investigated lipoprotein profiles measured by nuclear magnetic resonance (NMR) spectroscopy and circulating MDA-LDL levels measured by ELISA in 25 male patients with CAD and 15 age-matched male controls. We selected subjects who had a serum LDL cholesterol<160 mg/dL. The MDA-LDL levels were significantly higher in the CAD group than in the control group (P=0.01) even though there was no significant difference in the LDL cholesterol levels between the two groups. NMR analysis demonstrated that the MDA-LDL levels were positively correlated with large and intermediate very low-density lipoprotein triglyceride and LDL particle concentrations, and negatively correlated with LDL diameter and large high-density lipoprotein cholesterol. The MDA-LDL levels were negatively correlated with flow-mediated dilatation of the brachial artery. CONCLUSIONS: The high concentrations of circulating MDA-LDL derived from the atherogenic lipoprotein profiles, which induce the exaggerated production of small dense LDL. The circulating MDA-LDL may impair endothelial function and play an important role in the pathogenesis of atherosclerosis.
Aged↗
Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH Study.
BACKGROUND: Recent clinical trials have demonstrated that aggressive lipid lowering by statins could prevent recurrent events after acute coronary syndrome (ACS). We hypothesized that this efficacy was caused by a significant reduction in plaque volume by aggressive LDL cholesterol (LCL-C) lowering. The present study investigated the effect of early statin treatment on plaque volume of a nonculprit lesion by serial volumetric intravascular ultrasound in patients with ACS. METHODS AND RESULTS: Seventy patients with ACS were enrolled. All patients underwent emergency coronary angiography and percutaneous coronary intervention (PCI). They were randomized to intensive lipid-lowering therapy (n=35; atorvastatin 20 mg/d) or control (n=35) groups after PCI. Volumetric intravascular ultrasound analyses were performed at baseline and 6-month follow-up for a non-PCI site in 48 patients (atorvastatin, n=24; control, n=24). LDL-C level was significantly decreased by 41.7% in the atorvastatin group compared with the control group, in which LDL-C was increased by 0.7% (P<0.0001). Plaque volume was significantly reduced in the atorvastatin group (13.1+/-12.8% decrease) compared with the control group (8.7+/-14.9% increase; P<0.0001). Percent change in plaque volume showed a significant positive correlation with follow-up LDL-C level (R=0.456, P=0.0011) and percent LDL-C reduction (R=0.612, P<0.0001), even in patients with baseline LDL-C <125 mg/dL. CONCLUSIONS: Early aggressive lipid-lowering therapy by atorvastatin for 6 months significantly reduced the plaque volume in patients with ACS. Percent change in plaque volume showed a significant positive correlation with percent LDL-C reduction, even in patients with low baseline LDL-C.
Acute Disease↗
Behavior of Ca(2+) waves in multicellular preparations from guinea pig ventricle.
Ca(+) waves have been implicated in Ca(2+) overload-induced cardiac arrhythmias. To deepen understanding of the behavior of Ca(2+) waves in a multicellular system, consecutive two-dimensional Ca(2+) images were obtained with a confocal microscope from surface cells of guinea pig ventricular papillary muscles loaded with fluo 3 or rhod 2. In intact muscles, no Ca(2+) waves were detected under the resting condition, whereas they were frequently observed during the rest immediately after high-frequency stimulations where cytoplasmic Ca(2+) concentration and Ca(2+) stored in the sarcoplasmic reticulum (SR) were gradually decreasing. The intervals of Ca(2+) waves increased as they occurred later, their amplitudes and velocities remaining unchanged. A SERCA inhibitor reversibly prolonged the wave intervals. In Na(+)-free/Ca(2+)-free medium where neither Ca(2+) influx nor Na(+)/Ca(2+) exchange took place, recurrent Ca(2+) waves emerged at constant intervals in each cell. These results are consistent with the conclusion that the loading level of the SR is critical for induction of Ca(2+) waves. Each cell independently exhibited its own regular rhythm of Ca(2+) wave with a distinct interval. These waves propagated in either direction along the longitudinal axis within a muscle cell, but seldom beyond the cell boundary. In contrast, in partially damaged muscles that showed spontaneous Ca(2+) waves at rest in normal Krebs solution, their propagation often was unidirectional, decreasing in frequency. In these cases, however, Ca(2+) waves rarely moved beyond the cellular boundary. The gradient of the cytoplasmic Ca(2+) concentration was suggested to be the cause of the one-way propagation.
Animals↗