Masashi Sakuma

Saga University, Сага Япония, Saga, Japan

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Publications (32)218.68 Total impact

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    ABSTRACT: Expression of the gene encoding the S100 calcium-modulated protein family member MRP-14 (also known as S100A9) is elevated in platelets from patients presenting with acute myocardial infarction (MI) compared with those from patients with stable coronary artery disease; however, a causal role for MRP-14 in acute coronary syndromes has not been established. Here, using multiple models of vascular injury, we found that time to arterial thrombotic occlusion was markedly prolonged in Mrp14-/- mice. We observed that MRP-14 and MRP-8/MRP-14 heterodimers (S100A8/A9) are expressed in and secreted by platelets from WT mice and that thrombus formation was reduced in whole blood from Mrp14-/- mice. Infusion of WT platelets, purified MRP-14, or purified MRP-8/MRP-14 heterodimers into Mrp14-/- mice decreased the time to carotid artery occlusion after injury, indicating that platelet-derived MRP-14 directly regulates thrombosis. In contrast, infusion of purified MRP-14 into mice deficient for both MRP-14 and CD36 failed to reduce carotid occlusion times, indicating that CD36 is required for MRP-14-dependent thrombosis. Our data identify a molecular pathway of thrombosis that involves platelet MRP-14 and CD36 and suggest that targeting MRP-14 has potential for treating atherothrombotic disorders, including MI and stroke.
    The Journal of clinical investigation 04/2014; · 15.39 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 01/2013; 15(1). · 4.44 Impact Factor
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    ABSTRACT: Glucagon-like peptide 1 (GLP-1), one of the incretin hormones, has been reported to increase positive inotropic activity in cardiac myocytes and protect against myocardial injury. However, the effects upon endothelial cells and the mechanisms involved are not fully understood. We assessed the hypothesis that GLP-1 has protective effects against inflammation and oxidative stress on human endothelial cells. The effects of the GLP-1 analog liraglutide upon TNF-α-induced injury of the human umbilical vein endothelial cells (HUVECs) were evaluated. First, ROS induced by TNF-α was measured by staining with CM-H(2)DCFDA. Intracellular ROS production of HUVECs was significantly decreased in a dose-dependent manner until 30 nM while liraglutide inhibited the induction of gp91(phox) and p22(phox), subunit of NADPH oxidase, by TNF-α. In addition, protein levels of SOD-2, catalase and GPx were significantly increased by liraglutide. Second, rapid translocation of PKC-α into the membrane following TNF-α was evident. Liraglutide significantly inhibited this very rapid TNF-α-induced translocation of PKC-α into membrane at 2.5 min. Third, liraglutide significantly inhibited NF-κB activation and upregulated I-κB family while phosphorylation of IKK-α/β, which is upstream of NF-κB signaling, was also downregulated after 15 min of TNF-α treatment. Finally, liraglutide inhibited apoptosis of HUVEC and expression of Pentraxin-3 induced by TNF-α. Liraglutide exerts marked anti-oxidative and anti-inflammatory effects on endothelial cells with inhibition of PKC-α, NADPH oxidase, NF-κB signaling and upregulation of protective anti-oxidative enzymes.
    Atherosclerosis 01/2012; 221(2):375-82. · 3.71 Impact Factor
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    ABSTRACT: After stent-related vascular injury, an inflammatory response triggers the mobilization of bone marrow-derived stem cells, including both endothelial and smooth muscle progenitors, leading to re-endothelialization as well as restenosis. It has been postulated that neutrophil-released matrix metalloproteinase-9 (MMP-9) induces stem cell mobilization. To elucidate the mechanistic link between inflammation and stem cell mobilization after coronary stenting. In 31 patients undergoing coronary stenting, we serially measured activated Mac-1 on the surface of neutrophils and active MMP-9 levels in the coronary sinus blood plasma, and the number of circulating CD34-positive cells in the peripheral blood. After bare-metal stent implantation (n=21), significant increases in the numbers of CD34-positive cells (maximum on post-procedure day 7, P<0.001), activated Mac-1 (at 48 h, P<0.001), and active MMP-9 levels (at 24h, P<0.001) were observed. However, these changes were absent after sirolimus-eluting stent implantation (n=10). In overall patients, the numbers of CD34-positive cells on day 7 (R=0.58, P<0.01) and activated Mac-1 at 48 h (R=0.58, P<0.01) were both correlated with active MMP-9 levels at 24h. Stimulation of activated Mac-1 on the surface of isolated human neutrophils produced active MMP-9 release in vitro. These results suggest that stent-induced activation of Mac-1 on the surface of neutrophils might trigger their MMP-9 release, possibly leading to the mobilization of bone marrow-derived stem cells. These reactions were substantially inhibited by sirolimus-eluting stents.
    International journal of cardiology 11/2011; 152(3):332-6. · 6.18 Impact Factor
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    ABSTRACT: The cellular and molecular processes that control vascular injury responses after percutaneous coronary intervention involve a complex interplay among vascular cells and progenitor cells that control arterial remodeling, neointimal proliferation, and re-endothelialization. Drug-eluting stents (DES) improve the efficacy of percutaneous coronary intervention by modulating vascular inflammation and preventing neointimal proliferation and restenosis. Although positive effects of DES reduce inflammation and restenosis, negative effects delay re-endothelialization and impair endothelial function. Delayed re-endothelialization and impaired endothelial function are linked to stent thrombosis and adverse clinical outcomes after DES use. Compared with bare-metal stents, DES also differentially modulate mobilization, homing, and differentiation of vascular progenitor cells involved in re-endothelialization and neointimal proliferation. The effects of DES on vascular inflammation and repair directly impact clinical outcomes with these devices and dictate requirements for extended-duration dual antiplatelet therapy.
    JACC. Cardiovascular Interventions 10/2011; 4(10):1057-66. · 1.07 Impact Factor
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    ABSTRACT: Telmisartan, an angiotensin II type 1 receptor blocker (ARB), acts as a partial agonist for peroxisome proliferator-activated receptor-γ, and thus improves abnormalities of glucose metabolism and hypertriglyceridaemia in addition to its documented blood pressure-lowering effects. Recently, it has been demonstrated that telmisartan also lowers the levels of total cholesterol and low-density lipoprotein (LDL) cholesterol levels. This study was designed to investigate the mechanism of cholesterol reduction. We measured serum levels of cholestanol, a cholesterol absorption marker, and lathosterol, a cholesterol synthesis marker, in 20 patients with both hypercholesterolaemia and hypertension. Ten patients were treated with telmisartan and the remaining 10 with fluvastatin. After 3 months of treatment, total and LDL cholesterol levels decreased in the telmisartan group (P<0.01 for both total and LDL cholesterol levels) and the fluvastatin group (P<0.001 for both total and LDL cholesterol levels). The change in cholestanol level after 3 months of treatment was positively correlated with the levels of total (R=0.72, P<0.05) and LDL cholesterol (R=0.81, P<0.01) in the telmisartan group. The change in lathosterol level was positively correlated with the levels of total (R=0.88, P=0.001) and LDL cholesterol (R=0.89, P=0.001) in the fluvastatin group. Our results suggest that the cholesterol-lowering effect of telmisartan might be caused by inhibition of cholesterol absorption, whereas that of statins is by inhibition of cholesterol synthesis. If confirmed, co-treatment with the two agents may be useful for synergistically lowering cholesterol in hypertensive patients.
    Journal of Clinical Pharmacy and Therapeutics 02/2011; 36(1):103-10. · 2.10 Impact Factor
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    ABSTRACT: After vascular injury such as stent implantation, it has been suggested that the inflammatory response triggers mobilization of bone marrow-derived stem cells including both endothelial and smooth muscle progenitor cells, leading to re-endothelialization as well as restenoisis.. It has been postulated that neutrophil-released matrix metalloproteinase-9 (MMP-9) induces stem cell mobilization. To elucidate the mechanistic linkage between inflammation and stem cell mobilization, we serially measured circulating CD34-positive mononuclear cells, binding of 8B2, an antibody recognizing activation dependent neoepitope of integrin Mac-1, on the surface of neutrophils and active matrix metalloproteinase (MMP)-9 levels in 30 patients undergoing coronary stenting. After implantation of bare-metal stents, significant increases in the number of CD34-positive cells (maximum at the day 7, P<0.001), 8B2 binding (at 48 h, P<0.001), and active MMP-9 level (at 24 h, P<0.001) were observed. However, these changes were absent after implantation of sirolimus-eluting stents. In all patients, MMP-9 level at 24 h was correlated with the number of CD34-positive cells at day 7 (R=0.38, P<0.05) as well as 8B2 binding at 48 h (R=0.42, P<0.01). In patients who were implanted bare-metal stents, multiple regression analysis showed that angiographic late lumen loss was independently predicted by the number of CD34-positive cells at day 7 (R=34, P<0.05), 8B2 binding at 48 h (R=0.38, P<0.01), and MMP-9 levels at 24 h (R=0.32, P<0.05). In human isolated neutrophils taken from 5 healthy volunteers, stimulation of Mac-1 neoepitope by 8B2 antibody induced activated MMP-9 peoduction more than isotype control (P<0.01). Vascular injury by stent implantation may locally produce MMP-9, possibly leading to mobilization of bone marrow-derived stem cells, and subsequently to restenosis. Activation of neutrophil Mac-1 may greatly contribute to MMP-9 production. Excessive inhibition of these reactions by drug-eluting stents raise novel issues of present drug-eluting stents such as re-endothelialization failure.
    Circulation 01/2011; · 15.20 Impact Factor
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    ABSTRACT: To investigate whether the presence of decay-accelerating factor (or CD55), an intrinsic complement regulator, protects against the development of vascular disease, given that complement activation can affect leukocytes and platelets. Leukocyte-platelet complexes are critical for the initiation and progression of atherosclerosis and restenosis; however, the mechanism by which these processes promote vascular injury is incompletely defined. We performed femoral artery wire injury in Daf1(-/-) mice and their wild-type controls. Leukocyte accumulation, cellular proliferation, and neointimal thickening were enhanced in Daf1(-/-) mice versus wild-type mice. Deficiency of either the C3a or the C5a receptor, respectively, reversed the increased vascular inflammation, cellular proliferation, and neointimal formation in Daf1(-/-) mice. Decay-accelerating factor control of C3a and C5a generation and prevention of the binding of these activation fragments to the C3a and C5a receptors are critical for the biological response to vascular injury. Targeting the C3a and C5a receptors may be useful for the prevention of neointimal hyperplasia.
    Arteriosclerosis Thrombosis and Vascular Biology 03/2010; 30(6):1196-202. · 6.34 Impact Factor
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    ABSTRACT: Myeloid-related protein (MRP)-8 (S100A8) and MRP-14 (S100A9) are members of the S100 family of calcium-modulated proteins that regulate myeloid cell function and control inflammation, in part, through activation of Toll-like receptor-4 and the receptor for advanced glycation end products. A transcriptional profiling approach in patients with acute coronary syndromes identified MRP-14 as a novel predictor of myocardial infarction. Further studies demonstrated that elevated plasma levels of MRP-8/14 heterodimer predict increased risk of first and recurrent cardiovascular events. Beyond its serving as a risk marker, whether MRP-8/14 participates directly in vascular inflammation and disease remains unclear. We evaluated vascular inflammation in wild-type and MRP-14-deficient (MRP-14(-/-)) mice that lack MRP-8/14 complexes with experimental arterial injury, vasculitis, or atherosclerosis. After femoral artery wire injury, MRP-14(-/-) mice had significant reductions in leukocyte accumulation, cellular proliferation, and neointimal formation compared with wild-type mice. In a cytokine-induced local Shwartzman-like reaction that produces thrombohemorrhagic vasculitis, MRP-14(-/-) mice had significant reductions in neutrophil accumulation, lesion severity, and hemorrhagic area. In response to high-fat feeding, mice doubly deficient in apolipoprotein E and MRP-8/14 complexes had attenuation in atherosclerotic lesion area and in macrophage accumulation in plaques compared with mice deficient in apolipoprotein E alone. This study demonstrates that MRP-8/14 broadly regulates vascular inflammation and contributes to the biological response to vascular injury by promoting leukocyte recruitment.
    Circulation 09/2009; 120(5):427-36. · 15.20 Impact Factor
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    ABSTRACT: Down-regulation of the forkhead transcription factor Foxp1 by integrin engagement controls monocyte differentiation in vitro. To determine whether Foxp1 plays a critical role in monocyte differentiation and macrophage functions in vivo, we generated transgenic mice (macFoxp1tg) overexpressing human FOXP1 in monocyte/macrophage lineage cells using the CD68 promoter. Circulating blood monocytes from macFoxp1tg mice have reduced expression of the receptor for macrophage colony-stimulating factor (c-Fms/M-CSFR), impaired migratory capacity, and diminished accumulation as splenic macrophages. Macrophage functions, including cytokine production, phagocytosis, and respiratory burst were globally impaired in macFoxp1tg compared with wild-type cells. Osteoclastogenesis and bone resorption activity were also attenuated in macFoxp1tg mice. In models of chemical and bacterial peritonitis, macFoxp1tg mice exhibited reduced macrophage accumulation, bacterial clearance, and survival. Enforced overexpression of c-Fms/M-CSFR reversed the cytokine production and phagocytosis defects in macFoxp1tg macrophages, indicating that repression of c-fms/M-CSFR is likely the dominant mechanism responsible for Foxp1 action in monocyte differentiation and macrophage function. Taken together, these observations identify down-regulation of Foxp1 as critical for monocyte differentiation and macrophage functions in vivo.
    Blood 10/2008; 112(12):4699-711. · 9.78 Impact Factor
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    ABSTRACT: In allograft rejection, recipient leukocytes and alloantibodies first target donor endothelial cells. Although the leukocyte integrin Mac-1 (alpha(Mbeta2), CD11b/CD18) facilitates cell-cell interactions among leukocytes and interactions between leukocytes and endothelial cells or platelets, its role in allograft survival and vasculopathy is incompletely defined. This study examined parenchymal rejection and graft arterial disease after total allomismatched cardiac transplantation (BALB/c donor heart and B6 recipients) in wild-type (WT) and Mac-1-deficient (Mac-1(-/-)) recipients. Recipient Mac-1 deficiency attenuated parenchymal rejection and significantly prolonged cardiac allograft survival from 8.3+/-1.3 days in WT recipient allografts (n=18) to 13.8+/-2.3 days in Mac-1(-/-) recipient allografts (n=6; P<0.0001). Accumulation of neutrophils and macrophages significantly decreased in Mac-1(-/-) compared with WT recipients. Adoptive transfer of WT but not Mac-1(-/-) macrophages to Mac-1(-/-) recipients exacerbated parenchymal rejection and reduced allograft survival; in contrast, adoptive transfer of WT neutrophils did not affect graft survival. Mac-1(-/-) macrophages expressed significantly lower levels of costimulatory molecules both in vivo and in vitro, and mixed lymphocyte reaction using alloantigen-primed Mac-1(-/-) macrophages resulted in significantly lower antigen-presenting function than for WT macrophages. Tumor necrosis factor-alpha production also fell in cultures with Mac-1(-/-) macrophages. Despite attenuation of acute rejection, recipient Mac-1-deficiency did not prevent late graft arterial disease. These studies demonstrate critical participation of Mac-1 in alloresponses during cellular allograft rejection. These observations establish a molecular target for modulating recipient responses to prolong graft survival.
    Circulation 05/2008; 117(15):1997-2008. · 15.20 Impact Factor
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    ABSTRACT: Using a transcriptional profiling approach, we recently identified myeloid-related protein 8/14 (MRP-8/14) to be expressed by platelets during acute myocardial infarction (MI). Elevated concentrations of MRP-8/14 are associated with a higher risk for future cardiovascular events in apparently healthy individuals but have not been assessed with respect to prognosis in patients with acute coronary syndrome. We performed a nested case-control study (n = 237 case-control pairs) among patients enrolled in the Pravastatin or Atorvastatin Evaluation and Infection Therapy: Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial (mean follow-up 24 months) to investigate the risk of cardiovascular death or MI associated with MRP-8/14 measured at 30 days after an acute coronary syndrome. Patients with cardiovascular death or MI after 30 days (cases) had higher median [25th, 75th percentile] MRP-8/14 levels than patients who remained free of recurrent events (5.6 [2.8, 13.5] mg/L vs 4.0 [1.9, 10.1] mg/L, P = .020). The risk of a recurrent cardiovascular event increased with each increasing quartile of MRP-8/14 (P-trend = 0.007) such that patients with the highest levels had a 2.0-fold increased odds (95% CI 1.1-3.6, P = .029) of a recurrent event after adjusting for standard risk indicators, randomized treatment, and C-reactive protein. Patients with elevated levels of MRP-8/14 and high-sensitivity C-reactive protein showed significantly increased risk of cardiovascular death or MI compared with patients with the lowest levels of both markers (adjusted odds ratio 2.1, 95% CI 1.2-3.8). Myeloid-related protein 8/14 may be a useful biomarker of platelet and inflammatory disease activity in atherothrombosis and may serve as a novel target for therapeutic intervention.
    American heart journal 02/2008; 155(1):49-55. · 4.65 Impact Factor
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    ABSTRACT: To assess the importance of the interaction between leukocyte integrin Mac-1 (a Mb 2) and platelet glycoprotein (GP) Ib-a for leukocyte recruitment after vascular injury and the effect of the neutralization of the Mac-1-GPIba interaction on cell proliferation and the neointimal hyperplasia triggered by the vascular injury. A peptide called M2 or anti-M2 antibody was developed to block the Mac-1-GPIba interaction. This peptide was injected and compared to a control-peptide in C57B1/6J mice submitted to vascular injury of the femoral artery with a guide wire. One, five or 28 days after the vascular injury, the femoral arteries were removed for morphometric and immunohistochemical analyses. The blocking of the Mac-1-GPIba interaction promoted a statistically significant reduction in the number of leukocytes in the neointimal layer on the first day after the vascular injury (control: 7.9+/-5.0% of the cell total versus anti-M2: 2.0+/-1.6%, p=0.021), as well as determined a statistically significant decrease in leukocyte accumulation in the neointimal layer on days 5 and 28 (control: 42.3+/-12.9% versus anti-M2: 24.6+/-10.8%, p=0.047 and control: 7.9+/-3.0% versus anti-M2: 3.3+/-1.3%, p=0.012; respectively). Cell proliferation in the neointimal layer of the vessel five days post-injury was reduced with the blocking of the Mac-1-GPIba interaction (control: 5.0+/-2.9% of the cell total versus anti-M2: 1.8+/-0.5%; p=0.043), along with a significant decrease in cell proliferation in the vessel neointimal layer 28 days post-injury (control: 3.8+/-1.7% versus anti-M2: 2.0+/-1.2%; p=0.047). The blocking of the Mac-1-GPIba interaction also determined a statistically significant decrease of the intimal thickening 28 days post-injury (control: 10,395+/-3,549 microm(2) versus anti-M2: 4,561+/-4,915 microm(2); p=0.012). Leukocyte recruitment after a vascular injury depends on the Mac-1-GPIba interaction and the neutralization of this interaction inhibits cell proliferation and neointimal formation.
    Arquivos brasileiros de cardiologia 02/2008; 90(1):54-63. · 1.32 Impact Factor
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    ABSTRACT: Experimental data and preliminary clinical studies suggest that lipid-lowering drugs might have a beneficial effect on restenosis after coronary angioplasty. Recently, statins have been focused on prevention of restenosis after coronary stent implantation. However, their benefit has not yet been established. The authors studied the effects of statins on stent restenosis. We compared retrospectively the quantitative coronary angiographic (QCA) variables between 62 dyslipidemic patients treated with statins (pravastatin or fluvastatin) and 62 normolipidemic patients, as a control, treated without statins after undergoing successful coronary stent implantation with 6-month follow-up angiography from May 1999 to December 2002. Major cardiac events were about the same in both groups. Each of the QCA variables before and immediately after coronary stenting was similar in the 2 groups. At follow-up angiography, however, minimal lumen diameter (MLD) (2.12 -/+ 0.73 vs 1.78 -/+ 0.7; p < 0.01) was larger in the statin group than in the normolipidemia group. Both restenosis rate (15% vs 31%; p = 0.05) and target lesion revascularization rate (10% vs 24%; p = 0.05) were lower in the statin group than in the normolipidemia group. Statin reduced restenosis rate. The efficacy of statins appears to be dependent on their pleiotropic effects on vascular wall rather than on lipid-lowering effects.
    Angiology 01/2007; 58(1):55-60. · 2.37 Impact Factor
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    ABSTRACT: Platelets participate in events that immediately precede acute myocardial infarction. Because platelets lack nuclear DNA but retain megakaryocyte-derived mRNAs, the platelet transcriptome provides a novel window on gene expression preceding acute coronary events. We profiled platelet mRNA from patients with acute ST-segment-elevation myocardial infarction (STEMI, n=16) or stable coronary artery disease (n=44). The platelet transcriptomes were analyzed and single-gene models constructed to identify candidate genes with differential expression. We validated 1 candidate gene product by performing a prospective, nested case-control study (n=255 case-control pairs) among apparently healthy women to assess the risk of future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) associated with baseline plasma levels of the candidate protein. Platelets isolated from STEMI and coronary artery disease patients contained 54 differentially expressed transcripts. The strongest discriminators of STEMI in the microarrays were CD69 (odds ratio 6.2, P<0.001) and myeloid-related protein-14 (MRP-14; odds ratio 3.3, P=0.002). Plasma levels of MRP-8/14 heterodimer were higher in STEMI patients (17.0 versus 8.0 microg/mL, P<0.001). In the validation study, the risk of a first cardiovascular event increased with each increasing quartile of MRP-8/14 (Ptrend<0.001) such that women with the highest levels had a 3.8-fold increase in risk of any vascular event (P<0.001). Risks were independent of standard risk factors and C-reactive protein. The platelet transcriptome reveals quantitative differences between acute and stable coronary artery disease. MRP-14 expression increases before STEMI, and increasing plasma concentrations of MRP-8/14 among healthy individuals predict the risk of future cardiovascular events.
    Circulation 06/2006; 113(19):2278-84. · 15.20 Impact Factor
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    ABSTRACT: Leukocyte-platelet interactions are critical in the initiation and progression of atherosclerosis as well as restenosis. Although the leukocyte integrin Mac-1 (alphaMbeta2, CD11b/CD18) has been implicated in the firm adhesion and transmigration of leukocytes at sites of platelet deposition, the precise alphaMbeta2 counterligand responsible for mediating adhesion-strengthening interactions between neutrophils and platelets in vivo has not previously been identified. Our previous studies have established the P201-K217 sequence in the alphaMI domain as the binding site for platelet glycoprotein (GP) Ibalpha. Here we report that antibody targeting of alphaM(P201-K217) reduced alphaMbeta2-dependent adhesion to GP Ibalpha but not other alphaMbeta2 ligands, including fibrinogen, intercellular adhesion molecule-1, and junctional adhesion molecule-3. Anti-alphaM(P201-K217) inhibited the firm adhesion of both human and murine leukocytes to adherent platelets under laminar flow conditions. In a mouse femoral artery wire injury model, antibody targeting of alphaM(P201-K217) reduced leukocyte accumulation after injury that was accompanied by inhibition of cellular proliferation and neointimal thickening. This study demonstrates that GP Ibalpha is a physiologically relevant ligand for alphaMbeta2 and that integrin engagement of GP Ibalpha is critical to leukocyte function and the biological response to vascular injury. These observations establish a molecular target for selectively disrupting leukocyte-platelet complexes that promote inflammation in thrombosis and restenosis.
    Circulation 12/2005; 112(19):2993-3000. · 15.20 Impact Factor
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    ABSTRACT: The purpose of this study was to assess local release of C-reactive protein (CRP) from atherosclerotic plaques or the vessel wall injured by stenting. Recent research has focused on the local production of CRP, especially in inflammatory atherosclerotic plaques. The study consisted of two separate protocols. In protocol 1, we measured serum high-sensitivity-CRP (hs-CRP) levels in coronary arterial blood sampled just distal and proximal to the culprit lesions in 36 patients with stable angina and 13 patients with unstable angina. In protocol 2, we measured serial serum hs-CRP levels and activated Mac-1 on the surface of neutrophils in both coronary sinus and peripheral blood in 20 patients undergoing coronary stenting. In protocol 1, CRP was higher in distal blood than proximal blood in both stable (p < 0.05) and unstable angina (p < 0.01). The translesional CRP gradient (distal CRP minus proximal CRP, p < 0.05) as well as the proximal CRP (p < 0.05) and distal CRP (p < 0.05) was higher in unstable angina than in stable angina. In protocol 2, the transcardiac CRP gradient (coronary sinus minus peripheral blood) and activated Mac-1 increased gradually after stenting, reaching a maximum at 48 h (p < 0.001 vs. baseline for both). There was a positive correlation between the transcardiac CRP gradient and activated Mac-1 at 48 h (r = 0.45, p < 0.01). C-reactive protein is an excellent marker for plaque instability or poststent inflammatory status, and its source might be the inflammation site of the plaque or the coronary arterial wall injured by stenting.
    Journal of the American College of Cardiology 07/2005; 46(2):239-45. · 14.09 Impact Factor
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    ABSTRACT: A 47-year-old woman was referred to our hospital because of cardiomegaly and pericardial effusion. She complained of a cough. Computed tomography, echocardiography, and magnetic resonance imaging showed a mass on the pericardium. Exploratory surgery revealed a solid tumor invading the pericardium over the aortic arch and main pulmonary artery. Histological examination indicated primary malignant pericardial mesothelioma. After 58 Gy radiation, the size of the tumor was temporarily reduced and the patient's symptoms disappeared. However, the tumor enlarged and her symptoms reappeared 7 months after temporary improvement. Eighteen months after the development of cough, the patient died suddenly.
    Journal of Cardiology 01/2005; 44(6):255-62. · 2.30 Impact Factor
  • Circulation Journal - CIRC J. 01/2005; 69(1):128-129.
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    ABSTRACT: This study aimed to determine whether the influence of the lipid profiles as a risk factor was different between patients with and without diabetes mellitus (DM). Two hundred and fifty-six consecutive patients who underwent coronary angiography because of suspected coronary artery disease (CAD) were retrospectively analyzed. They included 188 patients with CAD and 68 patients with chest pain syndrome (controls). Multiple logistic regression analysis showed that DM, low density lipoprotein-cholesterol (LDL-C) / high density lipoprotein-cholesterol (HDL-C) ratio, remnant-like lipoprotein particle-cholesterol (RLP-C) and RLP-C / HDL-C ratio could discriminate CAD patients from the controls. The most powerful discriminating factor was DM (OR: 4.17, 95% CI: 1.82-9.57, p=0.0007). In the subgroup of non-diabetic patients, hypertension, LDL-C / HDL-C ratio, RLP-C and RLP-C / HDL-C ratio could discriminate CAD. In diabetic patients, however, only TG could discriminate CAD. These results suggest that the contribution of dyslipidemia in the development of CAD may be different in patients with and without DM, at least in the Japanese population.
    Vascular Disease Prevention 12/2004; 2(1):11-16.

Publication Stats

701 Citations
218.68 Total Impact Points

Institutions

  • 2004–2013
    • Saga University
      • • Department of Cardiorogy
      • • Division of Cardiovascular & Renal Medicine
      Сага Япония, Saga, Japan
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2002–2011
    • Dokkyo Medical University
      • Division of Cardiology and Pneumology
      Tochigi, Tochigi-ken, Japan
  • 2008–2010
    • Case Western Reserve University School of Medicine
      Cleveland, Ohio, United States
    • University of São Paulo
      San Paulo, São Paulo, Brazil
  • 2004–2008
    • Brigham and Women's Hospital
      • • Department of Medicine
      • • Center for Brain Mind Medicine
      Boston, MA, United States
  • 2006
    • Millennium Pharmaceuticals Inc
      Boston, Massachusetts, United States