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ABSTRACT: BACKGROUND: Although systemic hypertension is closely associated with aortic aneurysm (AA) formation, there are many patients with AA without hypertension. In these patients, an inflammation-mediated progression of aneurysmal disease is likely responsible for AA growth and eventual rupture. Unfortunately, there remains no reproducible and durable small animal model of aortic aneurysmal disease, the development of which would enable the investigation of the pathophysiology of this vexing condition. The first aim was to establish a useful wild-type mouse model of AA with low mortality. The second aim was to use this model to assess the protective effect of azelnidipine, a new calcium channel blocker, against the progression of the AA independent of its antihypertensive effect. METHODS: Angiotensin II and β-aminopropionitrile (a lysyl oxidase inhibitor) were administrated subcutaneously in 7-week-old C57BL/6J mice using an osmotic minipump for 4 weeks to generate a wild-type mouse model of AA. Concurrently, azelnidipine (a calcium channel blocker) or a placebo was administrated orally for 4 weeks. Mice were humanely killed and assessed at the end of the 4 weeks of pharmacologic manipulation. RESULTS: The combined infusion of angiotensin II and β-aminopropionitrile induced degenerative aneurysm of the thoracic and/or abdominal aorta (11/12; 92%). The majority of aneurysms were located in the distal aortic arch and suprarenal abdominal aorta. Although there was no difference in systolic blood pressure between the control and azelnidipine-treated groups, azelnidipine significantly reduced the incidence of AA (2/11; 18%). Azelnidipine treatment reduced the pathologic findings normally associated with aneurysm formation within the aortic wall. Azelnidipine also reduced the number of macrophage antigen-3 (MAC-3)-positive cells in the periaortic adipose tissue and reduced the gene expression levels of tumor necrosis factor-alpha and matrix metalloproteinase-2 and -9 within the aortic wall. CONCLUSIONS: This study demonstrates that combined treatment with angiotensin II and β-aminopropionitrile induces degenerative AAs in wild-type mice, and azelnidipine prevents aneurysm progression via its anti-inflammatory effect.
The Journal of thoracic and cardiovascular surgery 03/2013; · 3.41 Impact Factor
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Michio Shimabukuro,
Yoichiro Hirata,
Minoru Tabata,
Munkhbaatar Dagvasumberel,
Hiromi Sato,
Hirotsugu Kurobe,
Daiju Fukuda,
Takeshi Soeki, Tetsuya Kitagawa,
Shuichiro Takanashi,
Masataka Sata
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ABSTRACT: OBJECTIVE: The impact of epicardial adipose tissue (EAT) over abdominal or overall adiposity on coronary artery disease (CAD) is currently unknown. We compared the association among EAT volume (EATV), cytokine/adipocytokine profiles in EAT and subcutaneous fat, and atherogenic CAD.Approach and Results-Paired samples were obtained from EAT and subcutaneous adipose tissue during elective cardiac surgery for CAD (n=50) or non-CAD (n=50). EATV was the sum of cross-sectional EAT areas, and visceral and subcutaneous fat areas were determined at the umbilicus level on computed tomography scans. CD68+, CD11c+, and CD206+ cells were counted using immunohistochemical staining. Cytokine/adipocytokine expression was evaluated using quantitative real-time polymerase chain reaction. Multivariate analysis indicated that male sex, age, diabetes mellitus, high triglycerides, and low high-density lipoprotein, and EATV index (EATV/body surface area, cm3/m2) were significant CAD predictors (corrected R2=0.401; P<0.001); visceral fat area, hypertension, smoking, low-density lipoprotein (140 mg/dL [3.63 mmol/L]) or statin use were not predictors. The EATV index positively correlated with the CD68+ and CD11c+ cell numbers and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3, interleukin-1β, and interleukin-1R expression; and negatively correlated with adiponectin expression in EAT. A multivariate analysis model, including CD68+ cells and interleukin-1β, and adiponectin expression in EAT strongly predicted CAD (corrected R2=0.756; P<0.001). CONCLUSIONS: EATV and macrophage and cytokine/adipocytokine signals in EAT strongly correlated with CAD. Our findings suggest that EATV and adipocytokine imbalance are strongly linked to human coronary atherosclerosis.
Arteriosclerosis Thrombosis and Vascular Biology 03/2013; · 6.37 Impact Factor
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ABSTRACT: OBJECTIVE: Thymectomy is often performed to secure an operative field in surgery for congenital heart defects in early infancy. However, how neonatal thymectomy affects the subsequent development of the immune system in humans remains unclear. We monitored patients for 3 years from the time of thymectomy that was performed during cardiac surgery in early infancy. METHODS: For up to 3 years, we monitored the number of circulating lymphocytes and the clinical course of the children who underwent complete (n = 17), partial, and no (n = 15) thymectomy during congenital heart defect surgery performed at less than 3 months of age. The titers of immunoglobulin-G produced in response to vaccinated viruses and phytohemagglutinin responses were also measured. RESULTS: Six months after surgery, the number of T cells, including CD4(+) and CD8(+) subpopulations, decreased in patients with complete but not partial thymectomy. The reduction in T-cell number persisted for 3 years, whereas the number of B cells did not change. In patients with complete thymectomy, the titers of immunoglobulin-G produced in response to vaccinated measles and rubella viruses were reduced, whereas the phytohemagglutinin-induced proliferation of T cells was not impaired. In addition, hospitalization frequency associated with infectious diseases increased in patients with complete but not partial thymectomy. CONCLUSIONS: The results revealed that complete thymectomy in early infancy reduces the number of circulating T cells and T-cell-mediated immune responses for at least 3 years, suggesting that the thymus should be at least partially preserved during surgery in early infancy to maintain protective immunity.
The Journal of thoracic and cardiovascular surgery 01/2013; · 3.41 Impact Factor
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Yoichiro Hirata,
Hirotsugu Kurobe,
Chika Nishio,
Kimie Tanaka,
Daiju Fukuda,
Etsuko Uematsu,
Sachiko Nishimoto,
Takeshi Soeki,
Nagakatsu Harada,
Hiroshi Sakaue, Tetsuya Kitagawa,
Michio Shimabukuro,
Yutaka Nakaya,
Masataka Sata
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ABSTRACT: Exendin-4 is a glucagon-like peptide-1 receptor agonist that has been used as a drug for treatment of type 2 diabetes. To investigate the effect of exendin-4 on the cardiovascular system, we investigated the impact of exendin-4 on neointimal hyperplasia of the femoral artery after vascular injury. We performed wire-mediated endovascular injury in C57BL/6 mice, followed by administration of exendin-4 24nmol/kg/day via infusion pump. Four weeks after the injury, exendin-4 treatment significantly attenuated neointimal hyperplasia of the injured artery, although it did not affect glucose metabolism and lipid profile in wild-type mice. Immunofluorescence study revealed abundant expression of GLP-1 receptor on α-smooth muscle actin-positive cells in the injured vessel. Cell proliferation assay using rat aortic smooth muscle cells showed that exendin-4 reduced PDGF-BB induced smooth muscle cell proliferation through the cAMP/PKA pathway. Exendin-4also inhibited TNFα production by peritoneal macrophages in response to inflammatory stimulus. Our findings indicate that a GLP-1 receptor agonist attenuated neointimal formation after vascular injury.GLP-1 receptor agonists or drugs that raise endogenous GLP-1 level might be effective in the treatment of vascular diseases.
European journal of pharmacology 12/2012; · 2.59 Impact Factor
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Yoichiro Hirata,
Hirotsugu Kurobe,
Etsuko Uematsu,
Shusuke Yagi,
Takeshi Soeki,
Hirotsugu Yamada,
Daiju Fukuda,
Michio Shimabukuro,
Mizuho Nakayama,
Kunio Matsumoto,
Yoshiki Sakai, Tetsuya Kitagawa,
Masataka Sata
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ABSTRACT: Injury to the heart can result in cardiomyocyte hypertrophy, fibrosis, and cell death. Myocarditis sometimes progresses to dilated cardiomyopathy. We previously reported that ONO-1301, a synthetic prostacyclin agonist with thromboxane-synthase inhibitory activity, promotes production of hepatocyte growth factor (HGF) from various cell types and ameliorates ischemia-inducedleft ventricle dysfunction in the mouse, rat and pig. Here, we investigatedthe therapeutic efficacy of ONO-1301 in a rat model of myosin-induced experimental autoimmune myocarditis, in which the heart transits from an acute inflammatory phase to a chronic dilated cardiomyopathy phase. Four weeks after myosin injection to Wistar rats, ONO-1301 (6mg/kg/day) was orally administered for 4 weeks (ONO-1301 group). Hemodynamic parameters and plasma brain natriuretic peptide (BNP) level were significantly improved by ONO-1301.Histological analysis revealed that capillary density in the myocardium was significantly increased by ONO-1301. ONO-1301 increased circulating endothelial progenitor cells (EPC) as determined by FACS analysis. These beneficial effects of ONO-1301 were partialy abrogated by a neutralizing anti-HGF antibody(8mg/kg/dose). These findings indicatebneficial effects of ONO-1301 in a ratexperimental autoimmune myocarditis model.
European journal of pharmacology 12/2012; · 2.59 Impact Factor
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Dagvasumberel Munkhbaatar,
Michio Shimabukuro,
Takeshi Nishiuchi,
Junji Ueno,
Shoichiro Takao,
Daiju Fukuda,
Yoichiro Hirata,
Hirotsugu Kurobe,
Takeshi Soeki,
Takashi Iwase, [......],
Toshiyuki Niki,
Koji Yamaguchi,
Yoshio Taketani,
Shusuke Yagi,
Noriko Tomita,
Hirotsugu Yamada,
Tetsuzo Wakatsuki,
Masafumi Harada, Tetsuya Kitagawa,
Masataka Sata
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ABSTRACT: BACKGROUND: Growing evidence suggests that epicardial adipose tissue (EAT) may contribute to the development of coronary artery disease (CAD). In this study, we explored gender disparities in EAT volume (EATV) and its impact on coronary atherosclerosis. METHODS: The study population consisted of 90 consecutive subjects (age: 63 +/- 12 years; men: 47, women: 43) who underwent 256-slice multi-detector computed tomography (MDCT) coronary angiography. EATV was measured as the sum of cross-sectional epicardial fat area on CT images, from the lower surface of the left pulmonary artery origin to the apex. Subjects were segregated into the CAD group (coronary luminal narrowing > 50%) and non-CAD group. RESULTS: EATV/body surface area (BSA) was higher among men in the CAD group than in the non-CAD group (62 +/- 13 vs. 33 +/- 10 cm3/m2, p < 0.0001), but did not differ significantly among women in the 2 groups (49 +/- 18 vs. 42 +/- 9 cm3/m2, not significant). Multivariate logistic analysis showed that EATV/BSA was the single predictor for >50% coronary luminal narrowing in men (p < 0.0001). Predictors excluded were age, body mass index, hypertension, diabetes mellitus, and hyperlipidemia. CONCLUSIONS: Increased EATV is strongly associated with coronary atherosclerosis in men.
Cardiovascular Diabetology 09/2012; 11(1):106. · 3.35 Impact Factor
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Tamotsu Kanbara,
Hirotsugu Kurobe,
Takashi Kitaichi,
Mikio Sugano,
Taisuke Nakayama,
Hajime Kinoshita,
Takashi Iwase,
Masafumi Akaike,
Masahiro Abe,
Masataka Sata,
Toshio Matsumoto, Tetsuya Kitagawa
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ABSTRACT: Purpose: Efficient and secure collection of CD34+ cells are crucial for the angiogenic therapies. We have developed autologous peripheral blood-mononuclear cell (MNC) transplantation induced by erythropoietin (rhEPO) for critical ischemic limbs. Methods: Seven patients, including five with arteriosclerosis obliterans, one with Buerger's disease and one with progressive systemic sclerosis, underwent ten cell therapies. The first administration of rhEPO was performed two weeks before apheresis, and the second administration and blood donation were performed one week before apheresis to activate bone marrow. MNCs including CD34+ cells, isolated from peripheral blood by apheresis, were immediately injected intramuscularly into ischemic limbs. Results: The number of peripheral blood-CD34 + cells had significantly increased from 1.32 ± 0.83/microL, before the rhEPO induction, to 1.86 ± 0.94/microL, before the apheresis. The number of transplanted MNCs ranged between 0.5 × 10(9) and 16.5 × 10(9), and that of CD34+ cells, between 0.1 × 10(6) and 12.7 × 10(6), accounting for 0.02%-0.1% of MNCs. There were no serious complications. Finger ulcers with Buerger's disease were significantly improved one month after the transplantations, but the same or other ulcer(s) appeared 2-6 months later. Three patients had an improvement in rest pain, and one patient extended maximum pain-free walking distance. Conclusions: Erythropoietin-induced autologous peripheral blood-MNC transplantation is a useful and safe alternative for ischemic limbs.
Annals of Vascular Diseases 01/2012; 5(1):52-60.
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Yoichiro Hirata,
Minoru Tabata,
Hirotsugu Kurobe,
Tatsuo Motoki,
Masashi Akaike,
Chika Nishio,
Mayuko Higashida,
Hiroaki Mikasa,
Yutaka Nakaya,
Shuichiro Takanashi,
Takashi Igarashi, Tetsuya Kitagawa,
Masataka Sata
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ABSTRACT: The purpose of this report was to assess the link between macrophage polarization in epicardial adipose tissue and atherosclerosis in patients with coronary artery disease (CAD).
Macrophage accumulation enhances chronic inflammation in adipose tissue, but macrophage phenotypic change in human epicardial adipose tissue and its role in atherogenesis are unknown.
Samples were obtained from epicardial and subcutaneous adipose tissue during elective cardiac surgery (CAD, n = 38; non-CAD, n = 40). Infiltration of M1/M2 macrophages was investigated by immunohistochemical staining with antibodies against CD11c and CD206, respectively. Expression of pro- and anti-inflammatory adipocytokines in adipose tissue was evaluated by real-time quantitative polymerase chain reaction.
Infiltration of macrophages and expression of pro- and anti-inflammatory cytokines were enhanced in epicardial fat of patients with CAD compared with that in non-CAD patients (p < 0.05). The ratio of M1/M2 macrophages was positively correlated with the severity of CAD (r = 0.312, p = 0.039). Furthermore, the expression of pro-inflammatory cytokines was positively correlated, and the expression of anti-inflammatory cytokines was negatively correlated with the ratio of M1/M2 macrophages in epicardial adipose tissue of CAD patients. By contrast, there was no significant difference in macrophage infiltration and cytokine expression in subcutaneous adipose tissue between the CAD and non-CAD groups.
The ratio of M1/M2 macrophages in epicardial adipose tissue of CAD patients is changed compared with that in non-CAD patients. Human coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue.
Journal of the American College of Cardiology 07/2011; 58(3):248-55. · 14.16 Impact Factor
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ABSTRACT: Although several approaches have been tried to improve the durability of cryopreserved valves, cellular restoration after thawing remains to be investigated. The aim of our study was to assess the functional restoration of endothelial cells of cryopreserved heart valves by in vitro culture for an alternative step to improving longevity.
Cryopreserved human umbilical vein endothelial cells (HUVECs) and porcine aortic cusps were cultivated for 14 days after thawing. Then the cellular activity of the enzymes cytosolic esterase and mitochondrial dehydrogenase was measured. The cellular viability of cryopreserved cusps was also assessed using confocal laser scanning microscopy.
The number of viable HUVECs decreased markedly after cryopreservation and thawing but recovered to pre-cryopreservation level after 14 days of culture. In contrast, the enzyme activity of the cryopreserved porcine aortic cusps showed recovery at 7 days of in vitro tissue culture after thawing. Confocal laser scanning microscopy findings showed that the cellular cytosolic esterase activity of cryopreserved cusps deteriorated after thawing but displayed considerable recovery by day 14 of culture.
The functional recovery of endothelial cells in cryopreserved heart valves seems to require tissue culture of at least 14 days. Ex vivo endothelial restoration of cryopreserved heart valves may add to heart valve durability.
General Thoracic and Cardiovascular Surgery 03/2011; 59(3):169-74.
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ABSTRACT: Two adult patients with previous transient cerebral ischemic attacks (TIAs) or chest oppression were referred for further investigation. A swaying pedicled tumor was detected in the left atrium of the former patient and in the left coronary cusp of the latter by echocardiography. The TIA, or angina-like attack, was anticipated to be caused by thromboembolism of the tumor. Both patients underwent tumor extirpation. The histological findings demonstrated that both tumors were benign papillary fibroelastoma limited to the endocardium/endothelium layer. In conclusion, early surgical resection of a cardiac papillary fibroelastoma should be performed.
General Thoracic and Cardiovascular Surgery 03/2011; 59(3):191-4.
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Yoichiro Hirata,
Hirotsugu Kurobe,
Masashi Akaike,
Fumio Chikugo,
Takaki Hori,
Yoshimi Bando,
Chika Nishio,
Mayuko Higashida,
Yutaka Nakaya, Tetsuya Kitagawa,
Masataka Sata
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ABSTRACT: It has been hypothesized that epicardial fat, a local visceral fat depot with close proximity to coronary arteries, may serve as a source of inflammatory cytokines and cells in coronary atherosclerotic lesions. Here, we characterized infiltration of inflammatory cells and expression of adipocytokines in epicardial adipose tissue in patients with and without coronary artery disease (CAD). Pare samples were obtained from epicardial and subcutaneous adipose tissue during elective cardiac surgery (CAD, n = 8; non-CAD, n = 9). Inflammatory cell infiltration was investigated by immunohistochemical staining using antibodies against CD3, CD4, CD8 and CD68. Expression of adipocytokines was evaluated by real-time quantitative reverse transcription-polymerase chain reaction. Infiltration of macrophages and CD8-positive T cells in the epicardial adipose tissue in the CAD group was greater than that in the non-CAD group. In contrast, there was no significant difference between the two groups in the number of inflammatory cells in subcutaneous adipose tissue. No statistical difference could be found between the CAD group and the non-CAD group in the expression levels of adiponectin and inflammatory cytokines in epicardial adipose tissue. Our findings suggest that inflammatory cell infiltration is enhanced in epicardial adipose tissue, but not in subcutaneous fat, in patients with coronary artery disease. Chronic inflammation in epicardial fat may influence the pathogenesis of coronary atherosclerosis.
International Heart Journal 01/2011; 52(3):139-42. · 1.16 Impact Factor
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Hirotsugu Kurobe,
Ken-ichi Aihara,
Mayuko Higashida,
Yoichiro Hirata,
Masako Nishiya,
Yuki Matsuoka,
Tamotsu Kanbara,
Taisuke Nakayama,
Hajime Kinoshita,
Mikio Sugano,
Eiki Fujimoto,
Ayako Kurobe,
Noriko Sugasawa,
Takashi Kitaichi,
Masashi Akaike,
Masataka Sata,
Toshio Matsumoto, Tetsuya Kitagawa
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ABSTRACT: Ezetimibe, an inhibitor of cholesterol intestinal absorption, is a lipid lowering agent. However, anti-atherogenic effects of ezetimibe have not been fully elucidated. Therefore, the objective in this study was to clarify the vascular protective effects of ezetimibe in patients with hypercholesterolemia.
Ezetimibe was administered to 20 patients with hypercholesterolemia (group E), and 20 age- and sex-matched patients with hypercholesterolemia were followed as controls (group C). Difference in metabolic profiles and cardiovascular surrogate markers before ezetimibe treatment and after 12 weeks of ezetimibe treatment were statistically evaluated.
Ezetimibe treatment significantly reduced serum levels of low-density lipoprotein cholesterol (LDL-C) and malondialdehyde-modified low-density lipoprotein (MDA-LDL). In addition, the values of body mass index, body weight, waist circumference, plasma HbA1c and urinary albumin were significantly decreased in group E compared to those in group C. On the other hand, high-density lipoprotein cholesterol (HDL-C) and adiponectin levels were significantly increased in group E compared to those in group C. The values of brachial-ankle pulse wave velocity (ba-PWV), mean arterial blood pressure (m-ABP), and % of flow-mediated dilation (FMD) were significantly improved in group E. Furthermore, ultrasonic studies demonstrated amelioration of the vascular stiffness of common carotid arteries in group E but not in group C. These vascular protective effects of ezetimibe were statistically correlated with the decreased values of MDA-LDL and MDA-LDL-to-LDL-C ratio but not with those of LDL-C.
Ezetimibe has a lipid lowering-independent vascular protective effect in patients with hypercholesterolemia through decreasing oxidative stress.
Journal of atherosclerosis and thrombosis 01/2011; 18(12):1080-9. · 2.69 Impact Factor
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ABSTRACT: Preferable surgical approaches to aortic diseases occurring between the aortic root and the arch in patients with functioning tracheotomy or permanent tracheostomy are described for securing adequate exposure and avoiding postoperative mediastinitis. Case 1: A 41-year-old man with Marfan syndrome presented with chronic type A thrombosed aortic dissection and severe aortic valve regurgitation. He had had a functional tracheostomy for managing respiratory function due to traumatic spinal cord damage. The heart and the ascending aorta were shifted to the right side of the chest and showed a significant counterclockwise rotation. Therefore, the reverse L-figure approach of a right-sided 3rd intercostal anterior thoracostomy and lower midline sternotomy was performed for Bentall operation. Case 2: A 76-year-old woman presented with thoracic aortic aneurysm of 11 cm in diameter. She had had a permanent tracheostomy with total laryngectomy. Therefore, cram shell approach was performed for total arch replacement. The 2 cases had no postoperative mediastinitis. These approaches are recommended for aortic diseases occurring in the ascending aorta or the aortic arch in patients with functioning tracheotomy.
Kyobu geka. The Japanese journal of thoracic surgery 12/2010; 63(13):1113-8.
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ABSTRACT: Recent evidence in the fields of surgery, emergency and critical care medicine indicates that strict glycemic control results in lower mortality. Hyperglycemia occurs frequently in patients with and without diabetes during cardiovascular surgery, especially during cardiopulmonary bypass. However, strict glucose control is difficult to achieve during cardiovascular procedures. To establish effective intensive insulin therapy during cardiovascular surgery, we conduct continuous blood glucose monitoring and employ automatic control by using an artificial endocrine pancreas (the STG-22, Nikkiso, Tokyo, Japan). In this review, we will outline the present status and problems of conventional glycemic control for perioperative cardiovascular surgery and introduce the new perioperative blood glucose management method that we are testing now. We will also discuss the importance of perioperative glycemic control for cardiovascular surgery as well as future prospects.
The Journal of Medical Investigation 08/2010; 57(3-4):191-204.
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The Journal of thoracic and cardiovascular surgery 01/2010; 139(1):238; author reply 238-9. · 3.41 Impact Factor
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Hirotsugu Kurobe,
Masahisa Urata,
Masaki Ueno,
Masaaki Ueki,
Shiro Ono,
Yuki Izawa-Ishizawa,
Yayoi Fukuhara,
Yu Lei,
Adiratna Mat Ripen,
Tamotsu Kanbara,
Ken-ichi Aihara,
Keisuke Ishizawa,
Masashi Akaike,
Frank J Gonzalez,
Toshiaki Tamaki,
Yousuke Takahama,
Masanori Yoshizumi, Tetsuya Kitagawa,
Shuhei Tomita
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ABSTRACT: Recent studies have shown that the cellular immune response in the development of vascular remodeling modulates the resulting pathological alterations. We show that hypoxia-inducible factor 1 (Hif-1) (specifically expressed in T cells) is involved in the immune response to vascular remodeling that accompanies arteriosclerosis.
To study the role of T cells in the development of vascular remodeling, femoral arterial injury induced by an external vascular polyethylene cuff was examined in mice lacking Hif-1 (specifically in T cells). We found that cuff placement caused prominent neointimal hyperplasia of the femoral artery in Hif-1- (T-cell)-deficient mice compared with that in control mice and that infiltration of inflammatory cells at the adventitia was markedly increased in the mutant mice. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice showed enhanced production of cytokines by activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice.
The results of this study revealed that Hif-1alpha in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of T cell-mediated immune response. Potential new therapeutic strategies that target Hif-1alpha are described.
Arteriosclerosis Thrombosis and Vascular Biology 12/2009; 30(2):210-7. · 6.37 Impact Factor
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ABSTRACT: We investigated the effects and possible mechanism of syngeneic bone marrow mononuclear cell (BM-MNC) transplantation on pulmonary arterial hypertension induced by monocrotaline.
Monocrotaline (80 mg/kg body weight) was administrated to C57BL/6 mice, and pulmonary arterial hypertension was induced 4 weeks later. Bone marrow mononuclear cells harvested from syngeneic donor mice were injected intravenously into those mice 4 weeks after monocrotaline administration. The ratio of right ventricular to septum plus left ventricular weight, the number of small pulmonary arteries, and medial thickness of pulmonary arteries were measured. Western immunoblotting of the lung tissue was performed to observe vascular endothelial growth factor and its receptor expression 1 week after BM-MNC transplantation. Vascular endothelial growth factor receptor-2 inhibitor was administered to pulmonary arterial hypertension mice simultaneously with BM-MNC transplantation.
The ratio of right ventricular to septum plus left ventricular weight increased, the number of pulmonary arteries decreased, and medial thickness increased significantly 4 weeks after monocrotaline injection compared with those of vehicle-injected mice. These indices of monocrotaline-injected mice improved significantly 4 weeks after BM-MNC transplantation compared with those of mice at 8 weeks after monocrotaline injection (0.22 +/- 0.02 versus 0.31 +/- 0.02; 17.1 +/- 2.6 versus 8.2 +/- 1.7; 7.7% +/- 2.2% versus 20% +/- 2.1%, respectively; p < 0.01). However, BM-MNCs were not incorporated into the lung at 1 week after transplantation, and significant vascular endothelial growth factor upregulation and without receptor expression was observed in lung tissue 1 week after transplantation. Improvement of pulmonary arterial hypertension was inhibited by simultaneous administration of vascular endothelial growth factor receptor-2 inhibitor with BM-MNC transplantation.
These results indicate that syngeneic BM-MNC transplantation improves monocrotaline-induced pulmonary arterial hypertension by favorable pulmonary artery remodeling through vascular endothelial growth factor upregulation.
The Annals of thoracic surgery 08/2009; 88(2):418-24. · 3.74 Impact Factor
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Ken-ichi Aihara,
Hiroyuki Azuma,
Masashi Akaike,
Hirotsugu Kurobe,
Nobuyuki Takamori,
Yasumasa Ikeda,
Yuka Sumitomo,
Sumiko Yoshida,
Shusuke Yagi,
Takashi Iwase,
Kazue Ishikawa,
Masataka Sata, Tetsuya Kitagawa,
Toshio Matsumoto
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ABSTRACT: Heparin cofactor II (HCII) specifically inactivates thrombin action at the injured vascular wall. We have reported that HCII is a protective factor against coronary in-stent restenosis and carotid atherosclerosis; however, it is unclear whether there is any correlation between plasma HCII levels and the development of peripheral arterial disease (PAD).
Plasma HCII activity and the ankle brachial pressure index (ABI) were determined in 494 elderly subjects with cardiovascular risk factors. PAD was diagnosed by ABI below 0.9, and 62 subjects were diagnosed with PAD. The relationship between factors that affect cardiovascular events and the prevalence of PAD was statistically evaluated.
Mean HCII activity in PAD subjects was significantly lower than in non-PAD subjects (87.5+/-19.7% v.s. 94.6+/-17.8%, p=0.009). Multivariate logistic regression analysis showed that age (odds ratio [OR]: 1.062, p=0.0016), current smoking (OR 3.028, p=0.002) and diabetes mellitus (OR 2.656, p=0.008) were independent and progressive determinants of PAD. In contrast, HCII was an independent inhibitory factor of PAD (OR: 0.982, p=0.048).
Plasma HCII activity is inversely related to the prevalence of PAD. HCII may function as the sole protective factor against PAD in elderly people with cardiovascular risk factors.
Journal of atherosclerosis and thrombosis 05/2009; 16(2):127-34. · 2.69 Impact Factor
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Pohoey Fan,
Kenya Kusunose,
Hirotsugu Yamada,
Takashi Todoroki,
Susumu Nishio,
Toshiyuki Niki,
Koji Yamaguchi,
Kunihiko Koshiba,
Shusuke Yagi,
Takashi Iwase,
Takeshi Soeki,
Tetsuzo Wakatsuki,
Masashi Akaike, Tetsuya Kitagawa,
Masataka Sata
Echocardiography 02/2009; 26(1):113. · 1.24 Impact Factor
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Kenya Kusunose,
Hirotsugu Yamada,
Takashi Todoroki,
Susumu Nishio,
Toshiyuki Niki,
Koji Yamaguchi,
Kunihiko Koshiba,
Shusuke Yagi,
Takashi Iwase,
Takeshi Soeki,
Tetsuzo Wakatsuki,
Masashi Akaike, Tetsuya Kitagawa,
Masataka Sata
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ABSTRACT: A 59-year-old man was admitted for dyspnea on exertion and edema. The patient did not have any pulmonary diseases that could cause dyspnea. Transesophageal echocardiography on the tilting bed with contrast infusion revealed a right-to-left shunt through the patent foramen ovale. Therefore, he was diagosed as platypnea-orthodeoxia syndrome due to the patent foramen ovale. Surgical closure was done and all of his symptoms had improved.
Echocardiography 12/2008; 26(1):114-7. · 1.24 Impact Factor
