Biomedical subjects

Yasushi Kitaura

Publications and source records attributed to Yasushi Kitaura.

At least 19 recordsLinked to original sources

PubMed2007

Thiamine attenuates the hypertension and metabolic abnormalities in CD36-defective SHR: uncoupling of glucose oxidation from cellular entry accompanied with enhanced protein O-GlcNAcylation in CD36 deficiency.

BACKGROUND AND OBJECTIVES: The spontaneous hypertensive rat (SHR) is a widely studied model of hypertension that exhibits metabolic abnormalities, which share features with the human metabolic syndrome. Genetic linkage studies have revealed a defective CD36 gene, encoding a membrane fatty acid (FA) transporter, in hyperinsulinemia of the SHR. However, there is no unifying mechanism that can explain these phenotypes as a consequence of a defective CD36 gene. Impaired fatty acid uptake is compensated by increased glucose uptake. We hypothesized that (1) the abundant intracellular glucose is not oxidized proportionally and (2) the correction of the uncoupling of glucose oxidation to its cellular entry might be effective against the pathophysiology of CD36-defective SHR. Therefore, we attempted to activate glucose oxidation with the repletion of thiamine, a coenzyme for multiple steps of glucose metabolism. METHODS AND RESULTS: In one series of experiments, intracellular glucose fate was assessed by the ratio of [(14)C]glucose/[(3)H]deoxyglucose radioactivity, which suggested that glucose oxidation was uncoupled from its cellular entry in SHR. Protein O-GlcNAcylation was intense in the hearts of CD36-defective SHR compared with that of wild-type CD36 rats [Wister Kyoto rats (WKY)], indicating the shunt of glucose through the hexosamine biosynthetic pathway (HBP). In another series of studies, 4-week-old SHR were maintained with water containing 0.2% thiamine for 10 weeks. Systolic blood pressure, plasma insulin and norepinephrine levels were significantly lower in the thiamine-group, as compared with the untreated-group. In epididymal adipose tissue, thiamine repletion down-regulated the expression levels of mRNA transcripts for UDP-N-acetylglucosamine:peptide glycosyltransferase, angiotensinogen, angiotensin type 1 receptor, transforming growth factor-beta1 and plasminogen activator inhibitor-1. CONCLUSIONS: The hearts of CD36-defective SHR exhibited uncoupling of glucose oxidation from its cellular entry, accompanied with the enhanced protein O-GlcNAcylation, suggesting increased glucose shunt through the HBP. Thiamine repletion in CD36-defective SHR resulted in (1) the correction of the uncoupling of glucose oxidation to its cellular entry, concomitant with reduced protein O-GlcNAcylation, (2) the down-regulation of the expression of mRNAs involved in HBP, the renin-angiotensin system and adipokines in epididymal adipose tissue, and (3) the attenuation of the hypertension and hyperinsulinemia. We propose that interventions targeting glucose oxidation with thiamine repletion may provide a novel adjunctive approach to attenuate metabolic abnormalities and related hypertension.

Acetylglucosamine↗

PubMed2007

Success rate of implantation and mid-term outcomes of the sirolimus-eluting stent.

BACKGROUND: The sirolimus-eluting stent (SES) is currently the sole drug-coated stent approved for use in Japan, but there are few reports on its safety and outcomes in Japan. METHODS AND RESULTS: From May 2004 to February 2005, a total of 297 patients with 402 lesions were treated with SES at 6 hospitals in the Kansai district. Follow-up angiography was performed in 82% of the patients and 80% of the lesions at 182+/-35 days after stenting. Coronary stenosis was evaluated using quantitative coronary angiography. Clinical and angiographic data were analyzed. Minimum lesion diameter was 0.75+/-0.52 mm and the reference diameter was 2.81+/-0.47 mm before stenting. The SES successfully dilated 99.5% of the lesions with few major adverse cardiac events. Restenosis occurred in 4.0% and the target lesion revascularization rate was 3.7%. Restenosis correlated with chronic hemodialysis, calcification, occlusion, ostial lesions, lesions kinked>45 degrees, right coronary artery (RCA) lesions and lesions at the ostium of the RCA. CONCLUSION: SES demonstrated a high rate of successful implantation with few complications, and mid-term outcomes were excellent. Patients with lesions at the ostium of the RCA or under chronic hemodialysis developed restenosis.

Adult↗

PubMed2006

Gender difference of atorvastatin's vasoprotective effect in balloon-injured rat carotid arteries.

The effect of estrogen on neointimal formation in injured rat arteries has been reported to be a sexual dimorphic effect. Recently, it has been reported that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exhibit vasoprotective effects, which are independent of their cholesterol-lowering effects. In this study, we examined the gender differences of atorvastatin's effect on neointimal formation in balloon-injured rat arteries. Male and female Sprague Dawley rats underwent gonadectomy and balloon injury of the carotid artery. Ovariectomized female, as well as intact and castrated male, rats exhibited marked neointimal formation. Treatment with atorvastatin significantly reduced neointimal formation at day 14 (14 days after injury) and NADPH oxidase-dependent superoxide production at day 2 in ovariectomy, but not in intact and castrated males. In ovariectomized rats, 7 days of atorvastatin treatment from days -3 to 3 but not from days 7 to 14 suppressed neointimal formation at day 14. In this study, we showed that atorvastatin's effect on neointimal formation was female-specific and was more marked in ovariectomized female rats. NADPH oxidase-dependent superoxide production may be involved in the mechanism of the sexual dimorphic response seen in response to atorvastatin treatment. Furthermore, the results suggest the importance of treatment in the early phase after vascular injury.

Animals↗

PubMed2006

Regional postsystolic shortening in patients with hypertrophic cardiomyopathy: its incidence and characteristics assessed by strain imaging.

BACKGROUND: Postsystolic shortening (PSS) is considered myocardial shortening after the point of aortic valve closure and can be observed physiologically in healthy individuals. However, the incidence and magnitude of PSS in myocardial disorders have not been investigated. OBJECTIVES: We performed strain imaging to characterize PSS in patients with hypertrophic cardiomyopathy (HCM) versus healthy individuals. METHODS: Thirty patients with HCM (22 men and 8 women; mean age 62+/-6 years) and 30 control subjects (20 men and 10 women; mean age 61 +/- 9 years) were studied. For both groups, patterns of myocardial strain curves were assessed by the 18-segment model using apical 2-chamber, 4-chamber, and long-axis views. PSS was defined if the peak strain existed beyond aortic valve closure. The severity of PSS was assessed as postsystolic index (strain amplitude beyond aortic closure divided by whole strain amplitude) for each segment. RESULTS: As compared with control subjects, patients with HCM had a greater isovolumic relaxation time (105 +/- 31 vs 74 +/- 28 milliseconds, P < .001), despite the comparable value of left ventricular ejection fraction (65 +/- 6% vs 65 +/- 4%, P = not significant). The number of segments having PSS was greater in patients with HCM than in control subjects (12.6 +/- 3.0 vs 8.4 +/- 3.7, P < .001). This was associated with greater values of postsystolic index in all segments for patients with HCM. In patients with HCM, the number of segments having PSS correlated significantly with the isovolumic relaxation time (r = 0.36, P < .05). CONCLUSIONS: Patients with HCM have more pathologic PSS, which may have etiologic contribution to the functional heterogeneity of this disease entity, especially diastolic dysfunction.

Aged↗

PubMed2006

Clinical evaluation of point-of-care-testing of heart-type fatty acid-binding protein (H-FABP) for the diagnosis of acute myocardial infarction.

The present study was carried out for clinical evaluation of point-of-care-testing (POCT) of heart-type fatty acid-binding protein (H-FABP), Rapicheck H-FABP, for the diagnosis of acute myocardial infarction (AMI), in comparison with conventional cardiac biochemical markers such as myoglobin, creatine kinase isoenzyme MB (CK-MB), and cardiac troponin T. Whole blood samples from patients with confirmed AMI (n = 53), patients with non-AMI cardiac diseases (n = 24), and patients with non-cardiac diseases with chest pain (n = 6) were used. When a test line appeared within 15 min after the addition of 150 microL of whole blood, it was designated to be positive for H-FABP. A control line indicates a proper use of the test. On the other hand, when no test line appeared, it was negative. In the superacute phase of AMI within 3 hours, the diagnostic sensitivity of H-FABP was 93.1%, which was the highest of the four markers compared here. The diagnostic specificity in the phase for H-FABP was 64.3%, while it was 100% with cardiac troponin T. The POCT of H-FABP is thought to be practical for the detection of cardiac damage and effective for the diagnosis of AMI in superacute phase within 3 hours and/or 6 hours.

Acute Disease↗

PubMed2006

Effects of dual-chamber pacing on regional myocardial deformation in patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: This study examined the effects of dual-chamber pacing (DDD) on regional myocardial deformation, as determined by echocardiographic strain and strain rate (SR) imaging, in patients with hypertrophic obstructive cardiomyopathy (HOCM). METHODS AND RESULTS: Fourteen patients (11 men, 3 women; mean age 55 +/-16 years) who had been on long-term DDD (mean period 7.4 +/- 2.1 years) underwent strain and SR imaging. Before and after DDD, the peak strain (%) and SR (s(-1)) during systole were assessed in 8 segments in 4 left ventricular (LV) walls. With DDD turned on, peak strain and SR were significantly increased in the basal anteroseptal (strain -10.2 +/- 6.8 to -1.0 +/- 6.4, p<0.005; SR -0.76 +/- 0.46 to 0.05 +/- 0.58, p<0.001) and septal segments (strain -11.2 +/- 8.9 to -2.2 +/- 7.7, p<0.005; SR -0.85 +/- 0.54 to -0.19 +/- 0.75, p<0.05), but not in the basal posterior (strain -15.0 +/- 13.0 to -13.4 +/- 9.2, p=NS; SR -1.37 +/- 0.57 to -1.93 +/- 0.65, p=NS) and lateral segments (strain -18.1 +/- 10.2 to -15.7 +/- 5.6, p=NS; SR -1.33 +/- 0.68 to -0.84 +/- 0.88, p=NS). These findings were associated with a modest, but significant, change in the LV pressure gradient (24 +/- 12 mmHg to 14 +/- 7 mmHg, p<0.001). CONCLUSIONS: In patients with HOCM, DDD appeared to produce myocardial lengthening in the basal septum during systole, which may have implications for the mechanism of reducing LV outflow obstruction during DDD.

Aged↗

PubMed2006

Angiotensin-II receptor blocker exerts cardioprotection in diabetic rats exposed to hypoxia.

BACKGROUND: Hypoxia caused by sleep apnea might be associated with an increased risk of cardiovascular events in subjects with metabolic syndrome. The aim of this study was to examine the effect of hypoxia on the left ventricular (LV) myocardium and evaluate the cardioprotective effect of an angiotensin-II receptor blocker (ARB) in diabetic rats. METHODS AND RESULTS: Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats at 30 weeks of age (n=30) were divided into 2 groups that were treated with vehicle or candesartan 0.2 mg x kg(-1) x day (-1). The animals were housed in a hypoxic gas chamber (oxygen, 10.0+/-0.5%, mean +/- standard deviation) for 2 weeks. Hypoxia increased right ventricular (RV) systolic pressure (hypoxia; 78+/-14 mmHg vs control; 22+/-5, p<0.05), but did not increase LV systolic pressure (131+/-23 mmHg vs 121+/-10). Hypoxia exacerbated the degeneration of cardiomyocytes, and accelerated the expression of hypoxia inducible factor-1alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) in the myocardium. Treatment with ARB decreased RV and LV pressures (46+/-7 and 100+/-18 mmHg, respectively), suppressed the expression of HIF-1alpha and VEGF, and preserved the fine structure of the LV myocardium. CONCLUSIONS: ARB exhibited cardioprotection under hypoxia, in part through the reduction of blood pressure and cytokine expression, in OLETF rats. Thus, ARB might be a potent agent for the treatment of diabetic patients with the complication of sleep apnea.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

Usefulness of tissue Doppler imaging for demonstrating altered septal contraction sequence during dual-chamber pacing in obstructive hypertrophic cardiomyopathy.

Dual-chamber pacing reduces left ventricular (LV) outflow obstruction in patients with obstructive hypertrophic cardiomyopathy (HC), the mechanism of which lies in pacing-induced paradoxic septal motion. This study was conducted to test the hypothesis that tissue Doppler imaging (TDI) could demonstrate changes in the septal contraction sequence during dual-chamber pacing in patients with HC. TDI was performed in 16 patients (5 women; mean age 63+/-11 years) who underwent dual-chamber pacing for 7.6+/-2.1 year. With and without pacing, the time to peak systolic myocardial velocity was measured from the basal, mid, and distal segments in the 4 different LV walls. Without pacing, there was almost no longitudinal segmental asynchrony. During pacing, however, marked longitudinal segmental asynchrony appeared, especially in the anteroseptal wall (from p=NS to p<0.01 by analysis of variance) and the ventricular septum (from p<0.05 to p<0.01), with the time to peak velocity extremely prolonged at the distal segments. This was associated with a modest but significant decrease in the LV pressure gradient (from 20+/-8 to 14+/-7 mm Hg, p<0.01). In patients with obstructive HC, altered septal contraction sequence accounts for the reduced LV outflow obstruction during dual-chamber pacing, which was clearly demonstrated by TDI.

Adult↗

PubMed2005

Comparison of frequency of thromboembolic events and echocardiographic findings in patients with chronic nonvalvular atrial fibrillation and coarse versus fine electrocardiographic fibrillatory waves.

In patients with nonvalvular atrial fibrillation, the electrocardiographic fibrillatory wave reflects the structural and electrical remodeling of the atria. This study examined whether the fibrillatory wave amplitude could predict the risk of thromboembolism and demonstrated that this amplitude was related to the duration of atrial fibrillation. We also showed that the presence of fine fibrillatory waves (<1 mm in amplitude) could predict the thromboembolic potential in patients with chronic nonvalvular atrial fibrillation.

Aged↗

PubMed2005

Active HSF1 significantly suppresses polyglutamine aggregate formation in cellular and mouse models.

Polyglutamine diseases are inherited neurodegenerative diseases characterized by misfolding and aggregation of proteins possessing expanded polyglutamine repeats. As overexpression of some heat shock protein (Hsp) suppresses polyglutamine aggregates and cell death, it is assumed that combined overexpression of Hsps will suppress that more effectively. Here, we examined the impact of active forms of heat shock transcription factor 1 (HSF1), which induces a set of Hsps, on polyglutamine inclusion formation and disease progression. We found that active HSF1 suppressed polyglutamine inclusion formation more significantly than any combination of Hsps in culture cells, possibly by regulating expression of unknown genes, as well as major Hsps. We crossed R6/2 Huntington disease mice with transgenic mice expressing an active HSF1 (HSF1Tg). Analysis of the skeletal muscle revealed that the polyglutamine inclusion formation and its weight loss were improved in R6/2/HSF1Tg mice. Unexpectedly, the life span of R6/2/HSF1Tg mice was significantly improved, although active HSF1 is not expressed in the brain. These results indicated that active HSF1 has a strong inhibitory effect on polyglutamine aggregate formation in vivo and in vitro.

Adenoviridae↗

PubMed2005

Vascular endothelial growth factor-expressing mesenchymal stem cell transplantation for the treatment of acute myocardial infarction.

OBJECTIVE: Vascular endothelial growth factor (VEGF) plays an important role in inducing angiogenesis. Mesenchymal stem cells (MSCs) may have potential for differentiation to several types of cells, including myocytes. We hypothesized that transplantation of VEGF-expressing MSCs could effectively treat acute myocardial infarction (MI) by providing enhanced cardioprotection, followed by angiogenic effects in salvaging ischemic myocardium. METHODS AND RESULTS: The human VEGF165 gene was transfected to cultured MSCs of Lewis rats using an adenoviral vector. Six million VEGF-transfected and LacZ-transfected MSCs (VEGF group), LacZ-transfected MSCs (control group), or serum-free medium only (medium group) were injected into syngeneic rat hearts 1 hour after left coronary artery occlusion. At 1 week after MI, MSCs were detected by X-gal staining in infarcted region. High expression of VEGF was immunostained in the VEGF group. At 28 days after MI, infarct size, left ventricular dimensions, ejection fraction, E wave/A wave ratio and capillary density of the infarcted region were most improved in the VEGF group, compared with the medium group. Immunohistochemically, alpha-smooth muscle actin-positive cells were most increased in the VEGF group. CONCLUSIONS: This combined strategy of cell transplantation with gene therapy could be a useful therapy for the treatment of acute MI.

Actin Cytoskeleton↗

PubMed2005

Intraventricular dyssynchrony may play a role in the development of mitral regurgitation in dilated cardiomyopathy.

BACKGROUND: The development of functional mitral regurgitation (MR) in dilated cardiomyopathy (DCM) has been attributed to altered left ventricular (LV) geometry and annular dilatation. We propose the hypothesis that intraventricular dyssynchrony may play a role in the development of MR in DCM. METHODS AND RESULTS: Tissue Doppler echocardiography was performed in 32 DCM patients to assess the time from the onset of the QRS complex to the peak systolic myocardial strain (Ts) at 2 segments adjacent to the anterolateral and posteromedial papillary muscles from a short axis view. The time difference corrected by the RR interval (DeltaTs/ radicalRR) was used to evaluate dyssynchrony of these segments. There was no difference in the QRS duration (103 +/- 29 ms versus 95 +/- 22 ms, P = .38) or the presence of left bundle branch block (39% versus 14 %, P = .25) between 18 patients with MR and 14 patients without MR. However, DeltaTs/ radicalRR was significantly increased in the patients with MR, compared with those without MR (104 +/- 67 ms versus 5 +/- 16 ms, P < .0001). Stepwise multiple regression analysis showed that DeltaTs/ radicalRR was independent contributing factor of MR. CONCLUSION: Dyssynchrony of myocardial segments adjacent to the papillary muscles may disturb synchronized closure of the mitral leaflets and cause MR in DCM.

Adult↗

PubMed2005

Selective endothelin ET(B) receptor antagonist improves left ventricular function but exaggerates degeneration of cardiomyocytes in J2N-k hamsters.

BACKGROUND: Endothelin-1 (ET-1) receptor antagonist is expected to improve the prognosis of patients with heart failure, but the role of the ET(B) receptor in cardiac function and structure is complicated. In the present study the NADPH diaphorase activity and ET-1 content in the failing heart treated with ET(A) or ET(B) receptor antagonist were evaluated in a model of dilated cardiomyopathy. METHODS AND RESULTS: Selective ET(A) receptor antagonist, ABT-627 (10 mg/kg per day), or selective ET(B) antagonist, A-192621 (30 mg/kg per day), was given to 22-week-old J2N-k cardiomyopathic hamsters for 8 weeks. The effects of ABT-627 and A-192621 on cardiac function, left ventricular (LV) histology, ET-1 content and NADPH diaphorase activity in the LV were evaluated. Treatment with ABT-627, but not A-192621, significantly decreased ET-1 content and NADPH diaphorase activity. Although the improvement of LV function was modest, ABT-627 prevented tissue damage in J2N-k hamsters. In contrast, A-192621 worsened the degeneration of cardiomyocytes despite improving hemodynamic parameters. CONCLUSIONS: Selective ET(A) antagonist, but not ET(B) antagonist, reduced the ET-1 content as well as the NADPH diaphorase activity, and preserved the fine structure of LV myocardium in cardiomyopathic hamsters. Long-term blockade of ET(B) receptor might worsen the degeneration of cardiomyocytes through the ET-1/ET(A) system even if LV function could be improved.

Animals↗

PubMed2005

Mechanisms of combined treatment with celiprolol and candesartan for ventricular remodeling in experimental heart failure.

BACKGROUND: Both beta-adrenergic blockers and angiotensin-II receptor blockers were reported to improve the prognosis of patients with heart failure, but the efficacy of combination therapy with these agents has not been fully elucidated. Also the efficacy of celiprolol, a beta1-selective adrenoceptor antagonist with partial beta2-agonist properties, for heart failure treatment is still controversial. We examined the cardioprotective effects and mechanisms of the therapy with celiprolol or candesartan, an angiotensin-II receptor blockers and their combination in heart failure induced by isoproterenol (ISO). METHODS AND RESULTS: ISO 300 mg/kg was injected in rats to produce heart failure. Two months after the injection, the ISO-injected rats were divided into 4 groups (8 rats each) and treated for 4 weeks as follows: (a) vehicle; (b) celiprolol 10 mg/kg per day (BB); (c) candesartan 0.2 mg/kg per day (ARB); and (d) their combination BB+ARB. ISO significantly elevated left ventricular (LV) end-diastolic pressure, decreased peak-negative dP/dt and LV ejection fraction. BB and ARB similarly ameliorated cardiac dysfunction due to ISO, but BB+ARB were more potent than the individual therapies. Separately, ARB preserved the histological structure in LV myocardium. In contrast, BB ameliorated calcium handling, as shown by the increased ratio of SERCA2 to phospholamban protein, despite having little effect on the histology. CONCLUSION: Both celiprolol and candesartan showed cardioprotective effects in this heart failure model. The potential use of the combination treatment in heart failure might result in a synergistic effect through the different cardioprotective mechanisms of celiprolol and candesartan.

Animals↗

PubMed2005

Nifedipine enhances the cardioprotective effect of an angiotensin-II receptor blocker in an experimental animal model of heart failure.

This study was designed to examine the hypothesis that a calcium channel blocker nifedipine (CCB) could enhance the cardioprotective effect of an angiotensin-ll receptor blocker candesartan (ARB) in the treatment for heart failure. Isoproterenol (ISP) was injected into male rats at 300 mg/kg to produce progressive heart failure. Three months later, the rats were divided into 4 groups and treated for 4 weeks with 1) vehicle (n = 20), 2) ARB at 0.2 mg/kg/day (n = 6), 3) CCB at 10 mg/kg/day (n = 6), or 4) both drugs (n = 8). Rats injected with saline served as controls (n = 13). ISP caused severe myocardial degeneration and decreased the capillary density (D(cap)) of the left ventricular (LV) myocardium (mean +/- SD: 2,197 +/- 627 vs. 2,847 +/- 298 N/mm2 for normal controls), while increasing plasma thiobarbituric acid-reactive substances (TBARS; 3.6 +/- 1.1 vs. 1.9 +/- 0.5 nmol/ml). Although ARB therapy preserved cardiac morphology, it had little effect on D(cap) or oxidative stress. On the other hand, CCB decreased plasma TBARS and 4-hydroxy-2-nonenal protein expression in LV myocardium. Furthermore, the combination of CCB and ARB increased D(cap) and preserved the ultrastructure of LV myocardium, so this combination may be a useful option for the treatment of heart failure.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

Chronic hypoxia accelerates the progression of atherosclerosis in apolipoprotein E-knockout mice.

The aim of this study was to investigate the effect of chronic hypoxia on the development and progression of atherosclerosis in apolipoprotein E-knockout (apoE-KO) mice. Male and female apoE-KO mice (6 weeks old) and age- and sex-matched wild-type mice were kept under hypoxic conditions (10.0 +/- 0.5% O2) in a gas chamber or in room air for 3 weeks. Aortic atherosclerotic plaque was not observed in wild-type mice under normoxic or hypoxic conditions. In the apoE-KO mice, however, hypoxia induced proliferation of smooth muscle cells and plaque formation in the aorta, which were not observed under normoxic conditions. Although sexual dimorphism of the response to hypoxia was not observed, these hypoxia-induced atherogenic changes were accompanied by a significant increase of plasma low density lipoprotein (LDL) cholesterol and NADPH-dependent vascular superoxide (O2-) production. Furthermore, matrix metalloproteinase (MMP)-9 was activated in the aorta of apoE-KO mice. In conclusion, chronic hypoxia accelerated the development of atherosclerosis in apoE-KO mice, along with increased O2- production and activated MMP-9 in the aorta.

Animals↗

PubMed2004

Core protein of hepatitis C virus induces cardiomyopathy.

Hepatitis C virus (HCV) has been reported to be associated with cardiomyopathy. However, the mechanism of cardiomyopathy in chronic HCV infection is still unclear. Therefore, we investigate the development of cardiomyopathy in mice transgenic for the HCV-core gene. After the age of 12 months, mice developed cardiomyopathy that appeared as left ventricular dilatation, and systolic and diastolic dysfunction assessed by Doppler echocardiography. Histologically, hypertrophy of cardiomyocytes, cardiac fibrosis, disarray and scarcity of myofibrils, vacuolization and deformity of nuclei, myofibrillar lysis, streaming of Z-bands, and an increased number of bizarre-shaped mitochondria were found in HCV-core transgenic mice. These histological changes are just consistent with cardiomyopathy. In conclusion, the HCV-core protein directly plays an important role in the development of cardiomyopathy.

Actin Cytoskeleton↗

PubMed2004

Evidence of viral infection in the myocardium of American and Japanese patients with idiopathic dilated cardiomyopathy.

Enteroviruses have been implicated in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). Recently, the association of adenovirus or parvovirus with IDC has been reported. Viral infection in the myocardium of American and Japanese patients with end-stage IDC was evaluated. Myocardial specimens from 30 American patients with IDC and 47 Japanese patients with IDC were analyzed for the presence of cardiotropic viruses. The strand-specific detection of enteroviral ribonucleic acid (RNA) was performed to determine viral activity in hearts with IDC. Established reverse transcription-polymerase chain reaction (PCR) or PCR techniques were used to detect genomic sequences of influenza viruses, mumps virus, adenovirus, parvovirus, herpes simplex viruses, varicella-zoster virus, and Epstein-Barr virus. Enteroviral RNA was detected in 7 of the 30 American patients (23%) and in 15 of the 47 Japanese patients (32%). Minus-strand enteroviral RNA, an indicator of active enteroviral RNA replication, was demonstrated in 5 of 7 plus-strand-positive American patients (71%) and in 12 of 15 plus-strand-positive Japanese patients (80%). Sequence analysis revealed that the viruses detected were Coxsackie B viruses. No genomic sequences of other viruses were detected in the myocardium of either American or Japanese patients with IDC. Therefore, active group B Coxsackie virus RNA replication in the myocardium was demonstrated in a significant proportion of American and Japanese patients with end-stage IDC. There was no evidence of persistent infection by other viruses in hearts with IDC. Specific therapy should be designed for Coxsackie virus positive patients with IDC.

Adult↗