PubMed Health⌕ Search

Biomedical subjects

Issei Komuro

Publications and source records attributed to Issei Komuro.

At least 55 records · Page 3Linked to original sources
PubMed2006

G-CSF prevents the progression of atherosclerosis and neointimal formation in rabbits.

Granulocyte colony-stimulating factor (G-CSF) prevents left ventricular remodeling after myocardial infarction, but its effect on atherosclerosis is unknown. We examined two kinds of rabbit atherosclerosis models. Myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHL-MI) rabbits were treated with G-CSF or saline for 7 days from 14 months old. The vascular injury models were created by inflating angioplasty balloon in the iliac artery of rabbits and were divided into G-CSF and saline group. G-CSF significantly reduced the stenosis score of coronary artery and lipid plaque area of thoracic aorta in WHHL-MI rabbits at 4 weeks after the treatment. In the vascular injury model, G-CSF significantly prevented an increase in neointima/media ratio at 4 weeks after the treatment. G-CSF accelerated the reendothelialization of denuded arteries, and the pretreatment with nitric oxide synthase inhibitor significantly inhibited it. These results suggest that G-CSF has a therapeutic potential for the progression of atherosclerosis.

Animals↗
PubMed2006

New acquisition method to exclusively enhance the left side of the heart by a small amount of contrast material achieved by multislice computed tomography with 64 data acquisition system.

PURPOSE: To exclusively enhance the left side of the heart by a small amount of contrast material (CM) using rapid acquisition of multislice computed tomography (MSCT) with a 64-data acquisition system (DAS). MATERIALS AND METHODS: Forty consecutive subjects underwent MSCT (Light Speed VCT, GE) with 0.625mm slice thickness to evaluate coronary arteries. We first measured transit time, using 8ml of CM followed by 20ml saline. Dependent upon transit time, total volume of CM was determined, ranging from 45 to 63ml. After injection of CM at a rate of 4ml/s, followed by 47ml saline at 3.5ml/s, ECG-gated MSCT scanning was performed. The mean and standard deviation (S.D.) of CT values of the right atrium (RA), right ventricle (RV), left atrium (LA), left ventricle (LV), ascending aorta (Ao) and each coronary artery were measured. RESULTS: The mean of the CT values of the RA, RV, LA, LV, Ao, right coronary artery, left main, left anterior descending branch, and left circumflex branch were 225+/-76, 251+/-72, 353+/-55, 355+/-51, 352+/-34, 312+/-65, 296+/-57, 285+/-55, and 267+/-60HU, respectively. The corresponding S.D.s of the CT values were 39+/-22, 37+/-16, 32+/-7, 31+/-8HU, 25+/-5, 36+/-15, 31+/-13, 36+/-23, and 40+/-18HU, respectively. The mean of CT values of the RA and RV were significantly lower than those of the LA, LV, Ao, and each coronary artery (P<0.01), with excellent S.D.s. We could easily obtain three-dimensional coronary arterial and LV images without artifact of the RA and RV. CONCLUSIONS: Using 64-DAS MSCT, we successfully obtained exclusive enhancement of the left side of the heart using a small amount of CM.

Contrast Media↗
PubMed2006

Cardioprotective effects of granulocyte colony-stimulating factor in swine with chronic myocardial ischemia.

OBJECTIVES: The aim of this study was to investigate the effect of granulocyte colony-stimulating factor (G-CSF) on chronic myocardial ischemia in swine. BACKGROUND: We recently have reported that G-CSF prevents cardiac remodeling and dysfunction after acute myocardial infarction in mice and swine. It remains unclear whether G-CSF has beneficial effects on chronic myocardial ischemia. METHODS: An ameroid constrictor was placed on left circumflex coronary artery of swine. The presence of myocardial ischemia was verified at four weeks after the operation, and the animals were randomly assigned into the following two groups: 1) administration of vehicle (control group, n = 10), and 2) administration of G-CSF (10 microg/kg/day) for seven days (G-CSF group, n = 10). RESULTS: Echocardiographic examination revealed that the G-CSF treatment prevented left ventricular dilation and dysfunction at eight weeks after the operation. Stress echocardiography revealed that G-CSF ameliorated the regional contractility of chronic myocardial ischemia. Morphological analysis revealed that the extent of myocardial fibrosis of the ischemic region was less in the G-CSF group than in control group. There were more vessels and less apoptotic cells at the ischemic region of the heart of the G-CSF group than control group. Moreover, Akt1 was more strongly activated in the heart of the G-CSF group than control group. CONCLUSIONS: These findings suggest that G-CSF improves cardiac function of chronic myocardial ischemia through decreases in fibrosis and apoptotic death and an increase in vascular density in the ischemic region.

Animals↗
PubMed2006

Cellular senescence impairs circadian expression of clock genes in vitro and in vivo.

Circadian rhythms are regulated by a set of clock genes that form transcriptional feedback loops and generate circadian oscillation with a 24-hour cycle. Aging alters a broad spectrum of physiological, endocrine, and behavioral rhythms. Although recent evidence suggests that cellular aging contributes to various age-associated diseases, its effects on the circadian rhythms have not been examined. We report here that cellular senescence impairs circadian rhythmicity both in vitro and in vivo. Circadian expression of clock genes in serum-stimulated senescent cells was significantly weaker compared with that in young cells. Introduction of telomerase completely prevented this reduction of clock gene expression associated with senescence. Stimulation by serum activated the cAMP response element-binding protein, but the activation of this signaling pathway was significantly weaker in senescent cells. Treatment with activators of this pathway effectively restored the impaired clock gene expression of senescent cells. When young cells were implanted into young mice or old mice, the implanted cells were effectively entrained by the circadian rhythm of the recipients. In contrast, the entrainment of implanted senescent cells was markedly impaired. These results suggest that senescence decreases the ability of cells to transmit circadian signals to their clocks and that regulation of clock gene expression may be a novel strategy for the treatment of age-associated impairment of circadian rhythmicity.

Animals↗
PubMed2006

Effects of G-CSF on left ventricular remodeling and heart failure after acute myocardial infarction.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that promotes proliferation and differentiation of neutrophil progenitors. G-CSF also possesses immunomodulatory properties. G-CSF-induced hematopoietic stem cell mobilization is widely used clinically for transplantation. After it was recently reported that G-CSF mobilizes bone marrow stem cells (BMSCs) into the infarcted hearts and accelerates the differentiation into vascular cells and cardiac myocytes, myocardial regeneration utilizing mobilization of BMSCs by G-CSF is attracting the attention of investigators. In animal models, G-CSF prevents left ventricular remodeling and dysfunction after acute myocardial infarction, at least in part, through a decrease in apoptotic cells and an increase in vascular cells. Although it is controversial whether BMSCs mobilized by G-CSF can differentiate into cardiac myocytes, G-CSF-induced angiogenesis is indeed recognized in infarcted heart. The cardioprotective effects of G-CSF are recognized even in isolated perfused heart. In addition, G-CSF activates various signaling pathways such as Akt, extracellular signal-regulated kinase, and Janus kinase 2/signal transducer and activator of transcription 3 through G-CSF receptors in cardiac myocytes. These observations suggest that G-CSF not only induces mobilization of stem cells and progenitor cells but also acts directly on cardiomyocytes. Therefore, G-CSF may be utilized as a novel agent to have protective and regenerative effects on injured myocardium. Although the effects of G-CSF on the progression of atherosclerosis are still unclear, there is a possibility that G-CSF will become a promising therapy for ischemic heart diseases.

Animals↗
PubMed2006

Effect on coronary flow velocity reserve in patients with type 2 diabetes mellitus: comparison between angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor antagonist.

BACKGROUND: The effects of angiotensin antagonists on coronary circulation in type 2 diabetes are unclear. We aimed to assess whether 4 weeks of treatment with angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist improves coronary flow velocity reserve (CFVR) in patients with type 2 diabetes. METHODS: Twenty-four asymptomatic patients with type 2 diabetes were randomly assigned to temocapril (2 mg/d) or candesartan (8 mg/d). Coronary flow velocity reserve, calculated as the ratio of adenosine-induced hyperemic to basal coronary flow velocity, was measured with transthoracic Doppler echocardiography. Coronary flow velocity reserve measurement and venous blood sampling were performed before and after 4 weeks of treatment. We also obtained CFVR and venous blood data in the 8 healthy controls. RESULTS: Coronary flow velocity reserve was significantly lower in patients than controls (temocapril group 2.74 +/- 0.28, candesartan group 2.65 +/- 0.30, controls 3.53 +/- 0.23, P < .0001 for both, respectively). Blood pressure was reduced in both diabetic groups (n = 12 each) similarly 4 weeks after treatment. There were no significant differences between the 2 groups in venous blood data before or after treatment. However, CFVR increased significantly in the temocapril group (2.74 +/- 0.28 to 3.31 +/- 0.36, P < .0001), but not in the candesartan group (2.65 +/- 0.30 to 2.71 +/- 0.43, P = ns). CONCLUSIONS: Coronary flow velocity reserve in patients with type 2 diabetes improved after treatment with temocapril but not with candesartan, suggesting that angiotensin-converting enzyme inhibitor, but not angiotensin II type 1 receptor antagonist, might have beneficial effects on coronary microangiopathy associated with type 2 diabetes.

Aged↗
PubMed2006

Right coronary artery aneurysm with fistula to left ventricle: multislice CT appearance.

A 34-year-old male presented with prior radiographic evidence of enlargement of the right side of the heart. ECG-gated enhanced multislice CT was performed. Axial source images revealed a diffuse, hugely enlarged right coronary artery (RCA) aneurysm. The distal portion of the RCA flowed directly into the left ventricle (LV), suggesting an RCA to LV fistula. 3D volume rendered images clearly revealed a huge, enlarged RCA aneurysm from the proximal, mid, and distal portions of the RCA. The distal portion of the RCA aneurysm disappeared abruptly without showing distal branching, also suggesting an RCA to LV fistula.

Adult↗
PubMed2006

Regeneration of the endothelium as a novel therapeutic strategy for acute lung injury.

Acute lung injury (ALI) is characterized by the influx of protein-rich edematous fluid into the airspaces due to increased permeability of the alveolar-capillary barrier. Inflammatory mediators are thought to play a critical role in the pathogenesis of this disorder. In this issue of the JCI, Zhao et al. report that the forkhead box M1 (FoxM1) transcription factor induces endothelial regeneration and thereby restores endothelial barrier function after ALI (see the related article beginning on page 2333). Their findings raise the intriguing possibility that the promotion of endothelial regeneration may be a novel therapeutic strategy for ALI.

Animals↗
PubMed2006

Stent deformity caused by coronary artery spasm.

Previous studies have shown that coronary stents have radial strength above the pressure induced by coronary artery spasm. This case report describes a stent deformity caused by coronary artery spasm during percutaneous coronary intervention.

Angioplasty, Balloon, Coronary↗
PubMed2006

Intracoronary injection of granulocyte colony-stimulating factor ameliorates the progression of left ventricular remodeling after myocardial ischemia/reperfusion in rabbits.

BACKGROUND: Although granulocyte colony-stimulating factor (G-CSF) is known to prevent left ventricular (LV) remodeling after acute myocardial infarction (AMI), the best method of administration is unknown. METHODS AND RESULTS: A rabbit ischemia/reperfusion model was created and G-CSF was administered into the coronary artery immediately after reperfusion. The LV size and contraction were determined by echocardiography, and the extent of infarcted myocardium was measured by Masson-Trichrome staining. The benefits of intracoronary injection of G-CSF on LV remodeling were similar to subcutaneous injection. CONCLUSIONS: Direct intracoronary G-CSF injection may become a new therapy for AMI with lower adverse effects.

Acute Disease↗
PubMed2006

Application of hematopoietic cells to therapeutic angiogenesis.

Despite considerable progress in the field of cardiovascular medicine and surgery, ischemic heart disease is still the leading cause of death in advanced countries. In this context, it is no wonder why therapeutic angiogenesis, a way to ameliorate ischemic tissue from suffering dysfunction by increasing new blood vessels, gains so much attention from both clinicians and patients. In this review, we will briefly go through a decade of history in therapeutic angiogenesis including unraveling of its mechanisms, results obtained from clinical trials, and lessons learned from earlier investigations. We will then focus on an emerging, yet rapidly evolving field of hematopoietic cell therapy. Recent excellent studies seem to have brought us to the place where we might save so many patients from burden of ischemia, we should be aware that there are some controversies, and sometimes misunderstandings, regarding how or why this treatment does actually work, and what better way should we explore in order to get the best of its efficacy. With these caveats in mind, we will investigate the works elucidating the mechanisms and clinical efficacies of hematopoietic cell therapy.

Animals↗
PubMed2006

[Antisenescence as a novel therapeutic strategy for vascular aging].

Vascular cells have a finite lifespan when cultured in vitro and eventually enter an irreversible growth arrest state called "cellular senescence." It has been reported that many of the changes in senescent vascular cell behavior are consistent with the changes seen in age-related vascular diseases. Recently, senescent vascular cells have been demonstrated in human atherosclerotic lesions but not non-atherosclerotic lesions. Moreover, these cells express increased levels of proinflammatory molecules and decreased levels of endothelial nitric oxide synthase, suggesting that cellular senescence in vivo contributes to the pathogenesis of human atherosclerosis. One widely discussed hypothesis of senescence is the telomere hypothesis. An increasing body of evidence has established the critical role of the telomere in vascular cell senescence. More recent evidence suggests that telomere-independent mechanisms are implicated in vascular cell senescence. Activation of Ras, an important signaling molecule involved in atherogenic stimuli, induces vascular cell senescence and thereby promotes vascular inflammation in vitro and in vivo. Constitutive activation of Akt also induces vascular cell senescence. This novel role of Akt in regulating the cellular lifespan may contribute to various human diseases including atherosclerosis and diabetes mellitus. Although a causal link between vascular aging and vascular cell senescence remains elusive, a large body of data is consistent with cellular senescence contributing to age-associated vascular disorders. This review considers the clinical relevance of vascular cell senescence in vivo and discusses the potential of antisenescence therapy for human atherosclerosis.

Atherosclerosis↗
PubMed2006

[Molecular mechanisms of congestive heart failure].

Although heart failure is a final common consequence of various heart diseases and is a leading cause of mortality worldwide, the precise molecules and signaling pathways that mediate heart failure progression are largely undefined. In this review, we discuss about the potential mechanisms of heart failure focusing on three subjects, (i) myocardial ischemia, (ii) cardiac muscle cell death, and (iii) abnormalities in calcium handling. These factors are not mutually independent but considered to contribute to the pathogenesis of contractile dysfunction and heart failure in a cooperative manner. Elucidation of molecular mechanisms of heart failure will lead to the development of novel therapeutic strategies for heart diseases.

Animals↗