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Toyoaki Murohara

Publications and source records attributed to Toyoaki Murohara.

At least 19 recordsLinked to original sources
PubMed2007

Construction of multi-layered cardiomyocyte sheets using magnetite nanoparticles and magnetic force.

Heart tissue engineering requires construction of three-dimensional (3-D) tissues composed of cardiomyocytes (CMs) that are tightly connected to each other. The aim of this study was to construct "scaffold-less" multi-layered 3-D CM sheets using magnetic force-based tissue engineering (Mag-TE) and to evaluate the cell-to-cell functional connections within the CM sheets. Original magnetite cationic liposomes (MCLs) with a positive surface charge (which facilitate adsorption to the target cell surface) were taken up by CMs that were isolated from 2-day-old Wistar rats. When MCLs were added to the medium of CMs at magnetite concentrations of 25, 50, and 100 pg per cell, subsequent measurements showed that 7.2, 13.2, and 27.3 pg of magnetite were taken up per cell, respectively, after 4 h incubation at 37 degrees C. Further, no toxicity was observed after a 24 h incubation period. Using magnetically labeled CMs (magnetite concentration, 100 pg/cell), multi-layered CM sheets were constructed. Immunofluorescent staining of connexin43 demonstrated the presence of gap junctions within the CM sheets that were constructed by Mag-TE. Moreover, electrical connections within the CM sheets constructed by Mag-TE were confirmed using extracellular potential mapping. These results indicate that Mag-TE is a viable methodology for heart tissue engineering.

Animals↗
PubMed2007

Depletion of endothelial progenitor cells in the peripheral blood of patients with ulcerative colitis.

There is strong evidence to suggest that endothelial progenitor cells (EPCs) play a significant role in re-endothelialization and subsequent tissue repair. This study examined the role of EPCs in inflammatory bowel disease, a disease in which impairment of mucosal healing has been implicated. Peripheral blood mononuclear cells obtained from 50 patients with ulcerative colitis (UC), 29 patients with Crohn's disease (CD), 14 patients with infectious colitis, and 35 normal control subjects were cultured in EPC medium, harvested after 7 days, and characterized by immunocytochemistry and flow cytometry. Colony assay for hematopoietic progenitor cells was also performed. Patients with active UC had a significantly decreased number of circulating EPCs as compared with healthy controls (p=0.0013), patients with inactive UC (p=0.0099), patients with active CD (p=0.0235) and patients with infectious colitis (p=0.0002). On the other hand, patients with infectious colitis had a significantly increased number of circulating EPCs as compared with healthy controls (p=0.0406), patients with active UC (p=0.0002), and patients with active CD (p=0.0316). In patients with UC, the number of circulating EPCs was correlated with the serum hemoglobin levels (r=0.485, p=0.007) and inversely with the platelet count (r=-0.372, p=0.0382). The number of hematopoietic progenitor cell colonies was comparable among patients with UC, patients with CD, patients with infectious colitis, and healthy controls. Our observations indicate that the number of circulating EPCs in patients with UC is significantly reduced. Further studies are needed to define the mechanisms that underlie the reduction in the number of circulating EPCs and to better understand the pathophysiological consequences of this event in patients with UC.

Adult↗
PubMed2006

Therapeutic angiogenesis using novel vascular endothelial growth factor-E/human placental growth factor chimera genes.

BACKGROUND: Vascular endothelial growth factor-A (VEGF-A) promotes angiogenesis but causes adverse side effects such as edema or tissue inflammation. VEGF-E, found in the genome of the Orf virus, specifically binds to VEGF receptor-2 and shows mitotic activity on endothelial cells. Recently, we created two forms of VEGF-E and human placental growth factor (PlGF) chimera genes (VEGF-E chimera #9 and VEGF-E chimera #33), which are humanized genes with VEGF-E function but showing less antigenicity. METHODS AND RESULTS: We examined potential proangiogenic activities of these chimera genes. Four types of expression plasmids (pCDNA3.1-LacZ, phVEGF-A, pVEGF-Echimera#9, and pVEGF-Echimera#33) were administered in a rat model of hindlimb ischemia. Either pVEGF-Echimera#9, pVEGF-Echimera#33, or phVEGF-A significantly increased the ratio of ischemic/normal hindlimb blood-flow compared with the control pCDNA3.1-LacZ treated group (by 1.5-fold, 1.5-fold, and 1.4-fold, respectively, P<0.05). Histochemical staining by alkaline phosphatase also revealed that either pVEGF-Echimera#9, pVEGF-Echimera#33, or phVEGF-A increased the capillary density compared with the pCDNA3.1-LacZ treated group (1.4-fold, 1.5-fold, and 1.5-fold, respectively, P<0.05). Furthermore, immunostaining for anti-ED1 revealed that fewer macrophages had infiltrated in both pVEGF-Echimera#9 and pVEGF-Echimera#33 groups compared with the phVEGF-A group (P<0.05). CONCLUSIONS: Novel VEGF-E/human PlGF chimera genes, pVEGF-Echimera#9, and pVEGF-Echimera#33 significantly stimulated angiogenesis in response to tissue ischemia to an almost identical extent to that induced by phVEGF-A with fewer tissue inflammation responses.

Animals↗
PubMed2006

Heart slice NMR.

Nuclear magnetic resonance (NMR) spectroscopy of the heart is normally carried out using whole heart preparations under coronary perfusion. In such preparations, either radical changes in ionic composition of the perfusate or applications of numerous drugs would affect coronary microcirculation. This report communicates the first (31)P NMR spectroscopy study using a heart slice preparation (left ventricular slices) superfused with extracellular medium. The ratio of phosphocreatine concentration to ATP concentration was approximately 2.1. Also, intracellular pH and Mg(2+) concentration ([Mg(2+)](i)), estimated from the chemical shifts of inorganic phosphate and ATP, were comparable with those under retrograde perfusion. [Mg(2+)](i) was significantly increased by the removal of extracellular Na(+), supporting the essential role of Na(+)-coupled Mg(2+) transport in Mg(2+) homeostasis of the heart. Heart slice preparation could also be used to evaluate the potency of cardiac drugs, regardless of their possible effects on coronary microcirculation.

Adenosine Triphosphate↗
PubMed2006

Elastolytic cathepsin induction/activation system exists in myocardium and is upregulated in hypertensive heart failure.

Cathepsins are cysteine proteases that participate in various types of tissue remodeling. However, their expressions during myocardial remodeling have not been examined. In this study, we investigated their expressions in the left ventricular (LV) myocardium of rats and humans with hypertension-induced LV hypertrophy or heart failure (HF). Real-time PCR and immunoblot analysis revealed that the abundance of cathepsin S mRNA or protein in the LV tissues was greater in rats or humans with HF than in those with hypertrophy or in control subjects. Immunostaining showed that cathepsin S was localized predominantly to cardiac myocytes and coronary vascular smooth muscle cells, but also overlapped in part with macrophages. Elastic lamina fragmentations significantly increased in the LV intramyocardial coronary arteries of HF rats. The amount of elastolytic activity in the extract of the LV myocardium was markedly increased for HF rats compared with controls, and this activity was mostly because of cathepsin S. Although the amount of elastin mRNA was increased in the LV myocardium of HF rats, the area of interstitial elastin was not. The expression of interleukin 1beta was increased in the LV myocardium of HF rats, and this cytokine was found to increase the expression and activity of cathepsin S in cultured neonatal cardiomyocytes. These results suggest that cathepsin S participates in pathological LV remodeling associated with hypertension-induced HF. This protease is, thus, a potential target for therapeutics aimed at preventing or reversing cardiac remodeling.

Adult↗
PubMed2006

l-Caldesmon regulates proliferation and migration of vascular smooth muscle cells and inhibits neointimal formation after angioplasty.

OBJECTIVE: Light-type caldesmon (l-CaD) is a potent cytostatic and antiangiogenic protein that regulates cell growth and survival via modulation of the cell shape and cytoskeleton. The aim of this study is to explore the potential value of l-CaD for use as a cytostatic agent to inhibit neointimal formation after angioplasty by suppressing vascular smooth muscle cell (VSMC) growth and migration. METHODS AND RESULTS: We tested the cytostatic function of l-CaD in cultured VSMCs using assays for apoptosis, cell proliferation, and migration, and evaluated the expression pattern of relevant signaling proteins (focal adhesion kinase [FAK] and mitogen-activated protein kinases) in VSMCs. Transfection of adenoviral vector encoding l-CaD (Ad-l-CaD) resulted in progressive loss of actin stress fibers and cell retraction. Enzyme-linked immunosorbent assay demonstrated that Ad-l-CaD transfection increased the apoptosis rate by 75% and reduced BrdU uptake by 49%. Furthermore, transfection of Ad-l-CaD inhibited migration of VSMCs induced by platelet-derived growth factor-BB (PDGF) by 36% (P<0.05). Immunoblotting analysis revealed that l-CaD overexpression reduced PDGF-induced phosphorylation of both FAK and extracellular signal regulated-kinase (ERK). In balloon-injured rat carotid arteries, Ad-l-CaD transfection inhibited neointimal formation by 37% (P<0.05) without delaying re-endothelialization at 14 days. CONCLUSIONS: Overexpression of l-CaD suppressed cell growth and survival in VSMCs and inhibited neointimal formation after experimental angioplasty, partly by regulating the cytoskeletal tension-FAK-ERK axis.

Angioplasty↗
PubMed2006

The prostacyclin analog beraprost sodium augments the efficacy of therapeutic angiogenesis induced by autologous bone marrow cells.

Implantation of autologous bone marrow (BM) mononuclear cells (MNCs) has been shown to augment neovascular formation in ischemic tissues in experimental animals and in humans. Prostaglandin derivatives improve the symptoms of patients with critical limb ischemia, possibly by their vasodilating and antiplatelet actions. We therefore examined whether therapeutic angiogenesis by implantation of autologous BM-MNCs would be enhanced by beraprost sodium (BPS), using a rabbit ischemic hindlimb model. Ischemia was induced by surgical resection of the left femoral artery. Twenty-five New Zealand white rabbits were divided into four groups. The first group (BM group, n = 4) received autologous BM-MNCs (2 x 10(6)/animal) implanted into the ischemic tissue 1 week after limb ischemia. The second group (BM+BPS group, n = 8) received BPS injected into the dorsal skin (300 microg/kg daily) starting 1 week before limb surgery. This group received BM-MNC implantation 1 week after surgery. Daily injection of BPS was continued until the end of the protocol. The third group (BPS group, n = 8) received BPS injected into the dorsal skin (600 microg/kg daily) starting 1 week before limb surgery. The fourth group received saline as a control (n = 4). The extent of angiogenesis in the ischemic hindlimb was assessed using the angiographic score (AS), ischemic/normal limb calf blood pressure ratio (CBPR), and tissue capillary density. Four weeks after limb ischemia, the ischemic/normal CBPR was highest in the BM+BPS group, followed by the BPS, BM, and control groups (0.56 +/- 0.16, 0.51 +/- 0.25, 0.44 +/- 0.15, and 0.30 +/- 0.10, respectively). The AS was also the greatest in the BM+BP group, followed by the BM, BP, and S group (1.63 +/-0.21, 1.31 +/- 0.25, 1.26 +/- 0.21 and 0.80 +/- 0.10, respectively). The TCD was greatest in the BM+BP group, followed in by the BM, BP, and S group? (46 +/- 4.1, 34 +/- 0.7, 33 +/- 6.9, and 19 +/- 1.8 per field, respectively). BP treatment is an effective means to enhance the efficacy of therapeutic angiogenesis induced by autologous BM-MNCs implantation in ischemic hindlimb tissues.

Angiogenesis Inducing Agents↗
PubMed2006

Comparison of percutaneous coronary intervention with medication in the treatment of coronary artery disease in hemodialysis patients.

It has been reported that percutaneous coronary intervention (PCI) is beneficial for coronary artery disease (CAD) among the general population. However, its effects in patients who are on hemodialysis (HD) remain unclear. A prospective cohort study was performed to clarify whether PCI has a therapeutic advantage over medical therapy among HD patients with CAD. A follow-up study to 5 yr was conducted among 259 HD patients with ischemic heart disease. Mean follow-up was 39 mo. Patients were divided into three groups: 122 patients without significant stenosis, 88 patients who had significant stenosis and were treated with PCI, and 49 patients who had significant stenosis and were treated with medication only. The primary end point was cardiac death, and the secondary end point was all-cause death. The results showed that the 5-yr cardiac survival rate was 41.6% in the medication group, 77.1% in the PCI group (P = 0.0006), and 84.5% in the nonstenosis group (P < 0.0001). The 5-yr all-cause survival rate was 19.3% in the medication group, 48.4% in the PCI group (P = 0.004), and 64.3% in the nonstenosis group (P < 0.0001). Even after adjustment for other risk factors, effects of PCI on the risk for cardiac and all-cause death remained significant and independent (odds ratio 0.14; 95% confidence interval 0.08 to 0.25, P = 0.0006; and odds ratio 0.37; 95% confidence interval 0.26 to 0.54, P = 0.0062, respectively). Results were consistent when the therapeutic effect of PCI or medication was analyzed using propensity-matched patients. These data suggested that PCI could improve the prognosis of HD patients with CAD. PCI would be recommended for HD patients with CAD.

Aged↗
PubMed2006

The impact of the capability of circulating progenitor cell to differentiate on myocardial salvage in patients with primary acute myocardial infarction.

BACKGROUND: Circulating endothelial progenitor cells (EPCs) are known to be involved in vasculogenesis and mobilized after acute myocardial infarction (AMI). To test the hypothesis that the angiogenic function of EPCs affects post-myocardial infarction (MI) myocardial salvage, we evaluated the number and potential differentiation of EPCs and compared these data with clinical parameters 6 months after MI. METHODS AND RESULTS: Consecutive 51 patients (age, 61+/-8 years, mean+/-SD) with primary AMI who were successfully treated with stenting were enrolled. EPC identified as CD45low, CD34+, CD133+, and VEGFR2+ was quantified by a flow cytometry. The potential of EPCs to differentiate into endothelial cells (EPC differentiation) was also confirmed by the upregulation of CD31 and VEGFR2 after 7 days of culture. According to the proportion of EPC fraction, patients were divided into 2 groups (cut-off value=median). Although no difference was seen in myocardial damage shown by mean peak CK leakage and mean area at risk between the differentiated group (n=26) and nondifferentiated group (n=25), the number of attached cell was greater in differentiated group than in the nondifferentiated group (P=0.023). Left ventricular function and ischemic damaged area were assessed by scintigraphic images of (123)I-BMIPP in the acute phase and (99m)Tc-tetrofosmin in the chronic phase. We found that a greater increase in myocardial salvage (P=0.0091), decrease in end-systolic volume (P=0.012), and recovery of ejection fraction (P=0.011) occurred in the group with differentiated EPCs than in the nondifferentiated group. CONCLUSIONS: In patients with primary AMI, the capability of EPCs to differentiate influences the functional improvement and infarct size reduction, indicating that manipulation of EPCs could be a novel therapeutic target to salvage ischemic damage.

Aged↗
PubMed2006

Attenuation of cardiac dysfunction by a PPAR-alpha agonist is associated with down-regulation of redox-regulated transcription factors.

Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a key regulator of lipid and glucose metabolism and is implicated in inflammation. We investigated the effects of the PPAR-alpha activator fenofibrate on, as well as the role of redox-regulated transcription factors, in the development of left ventricular (LV) hypertrophy and heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed a high-salt diet and treated with either fenofibrate (30 or 50 mg/kg per day) or vehicle from 7 weeks of age. Fenofibrate inhibited the development of compensated hypertensive LV hypertrophy, attenuated the LV relaxation abnormality and systolic dysfunction, and improved the survival rate in DS rats. It also prevented a decrease in the ratio of reduced to oxidized glutathione and inhibited up-regulation of the DNA binding activities of the redox-regulated transcription factors NF-kappaB, AP-1, Egr-1, SP1, and Ets-1 induced in the left ventricle by the high-salt diet. Expression of target genes for these transcription factors, including those for adhesion molecules (VCAM-1, ICAM-1), cytokines (MCP-1), growth factors (TGF-beta, PDGF-B), and osteopontin, was also increased by the high-salt diet in a manner sensitive to treatment with fenofibrate. Furthermore, the infiltration of macrophages and T lymphocytes into the left ventricle and the increase in the plasma concentration of C-reactive protein were inhibited by fenofibrate. The PPAR-alpha activator fenofibrate thus attenuated the progression of heart failure and improved the survival rate in this rat model. These effects were associated with inhibition of the inflammatory response and of activation of redox-regulated transcription factors in the left ventricle.

Animals↗
PubMed2006

Upregulation of renal eNOS by high-sodium diet facilitates hypertension in doxorubicin-treated rats through enhanced oxidative stress.

It is known that renal nitric oxide (NO) is an important controller of urinary sodium excretion. A defect in the kidney's NO system could cause salt-sensitive hypertension. Since it has been demonstrated that doxorubicin binds to the reductase domain of endothelial NO synthase (eNOS) and generates superoxide in vitro, we tested our hypothesis that a high-sodium diet would upregulate the expression of eNOS and enhance oxidative stress in the kidney of doxorubicin-treated rats, resulting in a facilitation of hypertension. At 4 weeks after treatment with doxorubicin in Sprague-Dawley rats, the systolic blood pressure significantly increased only in the high-sodium diet group. The expressions of eNOS protein in the renal cortex and medulla were significantly higher in high-sodium groups than in normal-sodium groups, regardless of doxorubicin treatment. In rats treated with doxorubicin, a biomarker of oxidative damage 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunohistological staining of renal tissues showed strong staining of the proximal and distal tubules. In particular, rats with doxorubicin in the high-sodium diet group demonstrated a significant increase in urinary exertion of 8-OHdG as well as more prominently stained tubules against 8-OHdG antibody, but markedly lower urinary NO(x) excretion than in rats without doxorubicin, even than in the untreated, low-sodium group. In conclusion, these results indicate that the oxidative stress induced by doxorubicin impairs NO production in the kidney. As such, doxorubicin treatment appears to contribute to the development of salt-sensitive hypertension through reductive activation of upregulated eNOS by a high-sodium diet instead of NO production.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

Aberrant DNA demethylation in promoter region and aberrant expression of mRNA of PAX4 gene in hematologic malignancies.

The PAX4 gene, a member of the paired box (PAX) gene family, is thought to be involved in regulating the fate of beta-cells in the mammalian pancreas. We observed the aberrant expression of PAX4 mRNA in 10 of 15 hematologic cell lines analyzed by RT-PCR. The restoration of PAX4 gene expression after treatment with the demethylating agent 5-aza-2'-deoxycitidine, as well as bisulfite sequencing analysis, indicated that gene overexpression was caused by DNA demethylation at the promoter region. Such DNA demethylation also was observed in primary lymphoma (20 out of 45 patients) on combined bisulfite restriction assay (COBRA). Forced expression of the PAX4 gene in the HEK293 and SHSY/610 cell lines conferred positive effects on cell growth. This profile of PAX4 thus corresponds to that of a candidate oncogene in hematologic malignancies.

Azacitidine↗
PubMed2006

Combination of in vivo angiopoietin-1 gene transfer and autologous bone marrow cell implantation for functional therapeutic angiogenesis.

OBJECTIVE: Autologous bone marrow mononuclear cell (BM-MNC) implantation into ischemic tissues promotes angiogenesis, but a large amount of marrow aspiration is required, which is a major clinical limitation. Angiopoietin-1 (Ang-1) is requisite for vascular maturation during angiogenesis. We examined the impacts of combinatorial Ang-1 gene transfer and low-dose autologous BM-MNC implantation on therapeutic angiogenesis in a rabbit model of hind limb ischemia. METHODS AND RESULTS: Rabbits were divided into 4 groups: phosphate-buffered saline (control), 500 microg Ang-1 plasmid (Ang-1), 1 x 10(6) autologous BM-MNCs (BMC), and Ang-1 plasmid plus BM-MNCs (combination). The Ang-1 group had a greater angiographic score and capillary density compared with the control (P<0.05), but the Ang-1 gene therapy alone did not improve transcutaneous oxygen pressure (TcO2) and skin ulcer score. However, the combination group showed a significant improvement in not only angiographic score and capillary density (P<0.05) but also TcO2 (P<0.05) and skin ulcer score. These efficacies were greater in the combination group compared with the BMC group. CONCLUSIONS: This Ang-1 gene and BM-MNC combination therapy enhances not only quantitative but also qualitative angiogenesis in ischemic tissues. Moreover, the combination therapy will enable a reduction in the amount of BM aspiration required for significant therapeutic angiogenesis.

Angiography↗
PubMed2006

Plasma atrial natriuretic Peptide and brain natriuretic Peptide levels after radiofrequency catheter ablation of atrial fibrillation.

It has been reported that plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels are elevated in patients with atrial fibrillation (AF). The aim of this study was to investigate the change in these patients after pulmonary vein isolation (PVI). In 66 patients with paroxysmal AF (PAF) and without any structural heart disease, plasma ANP and BNP levels were measured before and 3 months after successful PVI. At baseline, in 14 patients, ANP and BNP levels were elevated, and in 52 patients, only BNP levels were elevated. There were no significant relations between the attack frequency or the duration of PAF episodes and ANP or BNP levels. Neither ANP nor BNP level at baseline was a valid predictor of AF recurrence. Even in 31 patients (47%) with recurrent PAF, attacks of PAF were significantly reduced. In 66 patients with elevated ANP and/or BNP levels at baseline, levels were significantly reduced after PVI independent of PAF recurrence (ANP: 69.0+/-23.0 vs 25.0+/-7.7 pg/ml, p<0.0001; BNP: 58.4+/-50.7 vs 22.5+/-27.1 pg/ml, p<0.0001). In 42 patients without AF recurrences, ANP and BNP levels were reduced to within the normal range. In conclusion, in patients with PAF without any structural heart disease, ANP and/or BNP levels were elevated. In those patients, relief of the AF burden by successful PVI significantly reduced elevated plasma ANP and BNP levels.

Atrial Fibrillation↗
PubMed2006

Usefulness of esophageal leads for determining the strategy of pulmonary vein ablation to avoid complications associated with the esophagus.

To avoid fatal complications after extensive pulmonary vein (PV) ablation, it has been proved important to comprehend the anatomic relation between the PVs and the esophagus. In 42 consecutive patients with atrial fibrillation, PV ostial isolation was performed using a basket catheter. The shortest distance and anatomic relation between the esophageal lead and PV ostium, determined by successful PV ostial isolation, was analyzed in biplane fluoroscopic views. In 18 left superior PVs (LSPVs) (43%), 13 left inferior PVs (32%) (LIPVs), and all the right PVs (group A), the shortest distance was > 10 mm in > or = 1 of the biplane fluoroscopic views. In 4 LSPVs (10%) and 2 LIPVs (5%) (group B), the shortest distance was < or = 5 mm in the fluoroscopic views. In the remaining PVs (group C), the esophagus was situated directly behind 10 LSPVs (24%) and 12 LIPVs (29%) (group C1), posteromedial to 1 LSPV (2%) and 9 LIPVs (22%) (group C2), and medial to 9 LSPVs (21%) and 5 LIPVs (12%) (group C3). The risk of esophagus-associated complications with ablation around the left PV ostia was suggested to be high in group B, very low in group A, and relatively low in group C. In group C3, extensive PV ablation might increase the risk of that complication. In conclusion, esophageal leads are useful for determining strategies for PV ablation to avoid esophagus-associated complications, because they enable comprehension of the anatomic relation between the PVs and the esophagus.

Atrial Fibrillation↗
PubMed2006

Prognostic value of pacing-induced mechanical alternans in patients with mild-to-moderate idiopathic dilated cardiomyopathy in sinus rhythm.

OBJECTIVES: The relation between the occurrence of pacing-induced mechanical alternans and prognosis in patients with mild-to-moderate idiopathic dilated cardiomyopathy (IDCM) in sinus rhythm was investigated prospectively. The myocardial expression of genes for Ca2+-handling proteins in such patients was also examined. BACKGROUND: Mechanical alternans occurs in some patients with severe heart failure, but the relation between the occurrence of mechanical alternans and prognosis in patients with IDCM has remained unknown. METHODS: Left ventricular (LV) pressure was measured during atrial pacing, and LV endomyocardial biopsy specimens were collected in 36 IDCM patients and 8 controls. Idiopathic dilated cardiomyopathy patients were divided into two groups consisting of 22 individuals who did not develop mechanical alternans at heart rates up to 140 beats/min (group A) and of 14 individuals who did (group B). The patients were followed up for a mean of 3.7 years. RESULTS: There was no significant difference in LV ejection fraction or the plasma concentration of brain natriuretic peptide between groups A and B. The myocardial abundance of ryanodine receptor 2 messenger ribonucleic acid (mRNA) was significantly lower in groups A and B than in controls, whereas that of sarcoplasmic reticulum Ca2+-ATPase mRNA was significantly lower in group B than in group A or controls. Stepwise multivariate analysis identified pacing-induced mechanical alternans as the strongest predictor of cardiac events. Event-free survival in group A was significantly greater than that in group B. CONCLUSIONS: The occurrence of pacing-induced mechanical alternans is a potentially useful indicator of poor prognosis in patients with mild-to-moderate IDCM in sinus rhythm.

Adult↗
PubMed2006

Klotho gene polymorphism may be a genetic risk factor for atherosclerotic coronary artery disease but not for vasospastic angina in Japanese.

BACKGROUND: The klotho gene, originally identified by insertional mutagenesis in mice, suppresses multiple aging phenotypes, including atherosclerosis. We tested the hypothesis that the G-395A polymorphism of the klotho gene is associated with increased risk for 2 types of ischemic heart disease in Japanese. METHODS: The study population consisted of 197 patients with coronary heart disease (CAD) who had >75% luminal diameter narrowing, 77 patients with vasospastic angina (VSA) without significant fixed coronary artery disease, and 331 healthy control subjects. RESULTS: The frequency of the A allele carriers of the klotho gene was significantly higher in the CAD group than in the control group (29.9% vs. 19.0%). The unadjusted odds ratio for CAD in the A allele carriers compared with the control group was 1.82 (p=0.004) and a traditional risk-adjusted logistic regression model revealed that the A allele was an independent predictor of CAD (odds ratio, 1.76; p=0.03). In contrast, the frequency of the A allele carriers was not significantly different in the VSA group (23.4%; adjusted odds ratio, 1.18. CONCLUSIONS: The -395A polymorphism of the human klotho gene may be a genetic risk factor for IHD and not for VSA.

Adult↗