尾崎 行男

Megakaryopoiesis is the hierarchical differentiation of hematopoietic stem cells into megakaryocytes. Differentiating megakaryocytes undergo maturation characterized by endomitosis and produce numerous platelets through proplatelet formation. C-type lectin-like receptor 2 (CLEC-2) is a podoplanin (PDPN) receptor mainly expressed on platelets and megakaryocytes. Deletion of platelet/megakaryocyte CLEC-2 causes thrombocytopenia in mice; however, its contribution to megakaryopoiesis remains unknown. Here, we show that megakaryopoiesis is promoted through the CLEC-2/PDPN interaction in the vicinity of arterioles in the bone marrow (BM). We have also identified PDPN-expressing BM arteriolar stromal cells, tentatively termed as BM fibroblastic reticular cell (FRC)-like cells. Platelet/megakaryocyte-specific CLEC-2 conditional knockout (cKO) mice showed a decrease in the number of immature megakaryocytes. CLEC-2 wild-type megakaryocyte expansion was augmented in vitro by the addition of recombinant PDPN, but not cKO megakaryocytes. Moreover, megakaryocyte colonies were colocalized with periarteriolar BM FRC-like cells in the BM. Coculture of megakaryocytes with BM FRC-like cells augmented megakaryocyte expansion, which was dependent upon the CLEC-2/PDPN interaction. Furthermore, we found that the CLEC-2/PDPN interaction induces BM FRC-like cells to secrete chemokine (C-C motif) ligand 5 (CCL5) to facilitate proplatelet formation. These observations indicate that a reciprocal interaction between CLEC-2 on megakaryocytes and PDPN on BM FRC-like cells contributes to the periarteriolar megakaryopoietic microenvironment in mouse BM.

The platelet receptor CLEC-2 is involved in thrombosis/hemostasis, but its ligand, podoplanin, is expressed only in advanced atherosclerotic lesions. We investigated CLEC-2 ligands in vessel walls. Recombinant CLEC-2 bound to early atherosclerotic lesions and normal arterial walls, co-localizing with vascular smooth muscle cells (VSMCs). Flow cytometry and immunocytochemistry showed that recombinant CLEC-2, but not an anti-podoplanin antibody, bound to VSMCs, suggesting that CLEC-2 ligands other than podoplanin are present in VSMCs. VSMCs stimulated platelet granule release and supported thrombus formation under flow, dependent on CLEC-2. The time to occlusion in a FeCl3-induced animal thrombosis model was significantly prolonged in the absence of CLEC-2. Because the internal elastic lamina was lacerated in our FeCl3-induced model, we assume that the interaction between CLEC-2 and its ligands in VSMCs induces thrombus formation. Protein arrays and Biacore analysis were used to identify S100A13 as a CLEC-2 ligand in VSMCs. However, S100A13 is not responsible for the above-described VSMC-induced platelet activation, because S100A13 is not expressed on the surface of normal VSMCs. S100A13 was released upon oxidative stress and expressed in the luminal area of atherosclerotic lesions. Suspended S100A13 did not activate platelets, but immobilized S100A13 significantly increased thrombus formation on collagen-coated surfaces. Taken together, we proposed that VSMCs stimulate platelets through CLEC-2, possibly leading to thrombus formation after plaque erosion and stent implantation, where VSMCs are exposed to blood flow. Furthermore, we identified S100A13 as one of the ligands on VSMCs.

Hypertrophic cardiomyopathy (HCM) has various morphological and clinical features. A decade has passed since the previous survey of the epidemiological and clinical characteristics of Japanese HCM patients. The Aichi Hypertrophic Cardiomyopathy (AHC) Registry is based on a prospective multicenter observational study of HCM patients. The clinical characteristics of 42 ambulant HCM patients followed up for up to 5 years were investigated. The primary endpoint was major adverse cardiac events (MACE), defined as death, non-fatal stroke, admission due to congestive heart failure (CHIP), or episodes of sustained ventricular tachycardia/fibrillation. The MACE-free survival during the 5-year follow-up period was 76% according to Kaplan Meier analysis. HCM-related death occurred in 3 (7%) patients and SCD occurred in 2 (5%) patients. Additionally, 3 (7%) patients were admitted to the hospital due to CHF. Meanwhile, sustained VT was detected in one (2%) of the patients who received ICD implantation and subsequently terminated with antitachycardia pacing using an ICD. The patients with HCM exhibiting left ventricular outflow obstruction (HOCM) had a slightly lower MACE-free survival rate than those with neither HOCM nor dilated-HCM (dHCM) (71% versus 81%, log-rank P = 0.581). Furthermore, the patients with dHCM demonstrated a significantly lower MACE-free survival rate than those with neither HOCM nor dHCM (33% versus 81%, log-rank P = 0.029). In the AHC Registry targeting current Japanese HCM patients, we demonstrated that many HCM patients continue to suffer from MACE despite the development of various treatments for HCM.

This study was conducted to demonstrate the seasonal change of floral organ number and morphology, and the effect of growth temperature on floral morphology in double-flowered cyclamen with petaloid-stamens. In plants grown under seasonal variable temperature, floral organ number and morphology in petaloid-stamen type of double flower changed as time passed, but the degrees of such changes differed depending on the line; there were two types, namely, "variable" and "relatively stable", in terms of the number of outer and inner petaloid-stamens throughout the flowering period. In the plants grown under different constant temperatures, the rate of complete petals (petaloid-stamens) to the total organs in whorl 3 was greatest at 15 degrees C, followed by the values at 25 degrees C and 20 degrees C. In contrast to complete petals, the rate of incomplete petals (petaloid-stamens) to the total organs in whorl 3 was greatest at 20 degrees C, followed by the values at 25 degrees C and 15 degrees C. The rate of stamen-like organs to the total organs in whorl 3 did not differ significantly among treatments, and the rate of stamens to the total organs in whorl 3 was suppressed only at 25 degrees C. Although the total numbers of stamens and stamen-like organs were similar at 15 degrees C and 20 degrees C, the developed positions of stamen-like organs and stamens were significantly different between 15 degrees C and 20 degrees C. Additional organs including stamens were produced inside the petaloid-stamen at 15 degrees C, while restoration of the stamen was induced at 20 degrees C. In conclusion, floral morphology shows seasonal change, and growth temperature affects the petaloidy of stamen in double-flowered cyclamen. However, the effect on petaloidy differs according to the line.

Objectives: Sphingosine 1-phosphate (SIP) is a bioactive sphingolipid mediator. Although the plasma SIP concentration is reportedly determined by cellular components, including erythrocytes, platelets, and vascular endothelial cells, the possible involvement of other factors, such as serum sphingomyelin (SM) and autotaxin (ATX), remains to be elucidated. Design and methods: We measured SIP using high-performance liquid chromatography (HPLC), SM and lysophosphatidic acid (LPA) using enzymatic assays, ATX antigen using a two-site enzyme immunoassay, and ATX activity using a lysophospholipase D activity assay. To fractionate the lipoproteins, plasma samples were separated using fast protein liquid chromatography (FPLC) utilizing a Superose 6 column. Results: The plasma SIP level was positively correlated with the levels of SM and lysophosphatidylcholine, but not with the level of phosphatidylcholine. Although SM was present in the very low-density lipoprotein (VLDL) fraction, neither the plasma SIP level nor the SM level was affected by feeding. The plasma SIP level was negatively correlated with the ATX activity. Although the incubation of 100 1.unol/L of sphingosylphosphorylcholine (SPC) with the serum resulted in a significant increase in the S1P level because of the presence of ATX, the physiological concentration of SPC did not mimic this effect. Conclusion: The plasma SIP level was affected by the serum SM level, while the possibility of ATX involvement in the increase in the plasma SW level was considered to be remote at least in healthy human subjects. (C) 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Several kinds of double-flowered cultivars have been produced from spontaneous mutants in Cyclamen persicum Mill. The morphology and number of organs in double flowers were investigated, and were categorized into three types: "petaloid-stamen type", "petaloid-sepal type", and "extra petals in whorl 2 type". Morphological observations showed that petaloid mutations of stamen and sepal did not appear together within an individual. In addition, three types of AG-like gene were isolated from single and petaloid-stamentype double-flower buds, and expressions in each whorl were compared. All AG-like genes were expressed in whorl 3 of single flowers, but not in that of petaloid-stamen-type double flowers. In whorl 4, although expressions of the three types of AG-like gene were observed in both single and double flowers, the expression of double flowers was lower than that of single flowers. These results suggest that naturally occurring double flowers of cyclamen can be explained by the ABC-model, and it is suspected that petaloidy of the stamen is caused by the repression of AG-like gene expression in whorl 3.

Individuals in northern populations of Lilium longiflorum in the Ryukyu Archipelago between Japan and Taiwan exhibit deep dormancy which is induced by high temperatures in the Summer, while plants of southern ecotypes and L. formosanum show no dormancy. In higher plants, 9-cis-epoxycarotenoid dioxygenase (NCED) is the critical enzyme for the regulation of abscisic acid (ABA) biosynthesis. The relationships between levels of expression of the LlNCED gene (GenBank Accession No. KC357734) and endogenous ABA levels were examined in 1-year-old seedlings of an L. formosanum population domesticated in Fukuoka (FFU) and in two L. longiflorum populations native to Pitouchiao (LPI), Taiwan, or Kikai Jima (LKI), Japan. The deduced amino acid sequences of the NCED proteins shared high identity with NCED proteins in other monocotyledons, and were closely related to enzymes in other members of the class Liliopsida. A high correlation was observed between levels of LlNCED gene expression and ABA concentration. Seedlings from LKI had the highest level of expression of LlNCED in August, while seedlings from FFU had the lowest level. Higher expression of the LlNCED gene in mid-Summer in the dormant population was related to higher endogenous concentrations of ABA. These results provide evidence that the induction of deep dormancy was initiated by the accumulation of ABA in dormant types of L. longiflorum, which was induced by high Summer temperatures.

With the delay of harvest stage, the carbohydrate content of flower petals and the diameter of flower buds increased, but the vase life was shortened. Effects of abscisic acid (ABA) and sucrose on preservation of cut lilies were related to the harvest stage. Due to the lower level of soluble sugars and other energy source in early harvested cut lilies, the sucrose pretreatment turned to be particularly effective for extending the vase life and increasing the flower fresh weight and bud diameter. For the cut flowers harvested at middle stage, pretreatment with sucrose or ABA separately enhanced the preservation effect, which was not observed when pretreated with the combination of sucrose and ABA. The preservation effect of the harvested flowers at the late development stage was increased by the ABA pretreatments including ABA alone or ABA and sucrose (ABA+Suc). ABA improved sucrose uptake from the pretreatment solution and increased soluble sugar contents in cut flower petals. Combined with sucrose pretreatment, addition of ABA alleviated leaf chlorosis symptom of cut flowers harvested in early period.

Although it is often considered as a senescence phytohormone, abscisic acid (ABA) at low concentration together with sucrose as pulsing solution displayed preservative effect on cut lily flowers. In order to further clarify the preservation mechanism of ABA, the effects of ABA pretreatment on physiological index and ethylene release were investigated. The addition of 2 mg.L-1 ABA to sucrose increased proline content in petals. This result suggested that ABA application resulted in water stress of the cut flowers to some extent. However the pretreatment of the cut lilies with ABA at 2 mg.L-1 delayed the degradation of soluble proteins, and promoted the activity of superoxide dismutase (SOD) enzyme, which decreased the damage to cells induced by reactive oxygen species (ROS). It was also found that the pretreatment with 2 mg.L-1 ABA inhibited ethylene release.

Hot water extracts of the medicinal mushroom Agaricus brasiliensis were investigated for their inhibition of platelet aggregation. The extracts significantly inhibited human platelet aggregation induced by adenosine 5'-diphosphate (ADP), but not by collagen or thrombin receptor-activating peptide. The extracts also had a significant inhibitory effect on shape change and intracellular calcium mobilization induced by ADP via inhibition of ADP binding to the P2Y(1) receptor. In addition, oral administration of the extracts resulted in prolonged tail bleeding time in mice. The marked antiplatelet activity of the mushroom extracts involving the P2Y(1) receptor suggests their potential therapeutic use against vascular disorders.

Detection of platelet activation in vivo is useful to identify patients at risk of thrombotic diseases. Platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) are used for this purpose; however, they are easily released upon the minimal platelet activation that occurs during sampling. Soluble forms of several platelet membrane proteins are released upon platelet activation; however, the soluble form of C-type lectin-like receptor 2 (sCLEC-2) has not yet been fully investigated. Western blotting with an anti-CLEC-2 antibody showed that sCLEC-2 was released from washed human platelets stimulated with collagen mimetics. To detect sCLEC-2 in plasma, we established a sandwich enzyme-linked immunosorbent assay (ELISA) using F(ab')2 anti-CLEC-2 monoclonal antibodies. Although plasma mixed with citrate, adenosine, theophylline and adenosine (CTAD) is needed for the PF4 and beta-TG assays, effects of anti-coagulants (EDTA, citrate and CTAD) on the sCLEC-2 ELISA were negligible. Moreover, while special techniques are required for blood sampling and sample preparation for PF4 and beta-TG assay, the standard blood collections procedures used in daily clinical laboratory tests have shown to suffice for sCLEC-2 analysis. In this study, we found that two forms of sCLEC-2 are released after platelet activation: a shed fragment and a microparticle-bound full-length protein, both of which are detected by the sCLEC-2 ELISA. The average concentration of sCLEC-2 in the plasma of 10 healthy individuals was 97 +/- 55 pg/ml, whereas that in the plasma of 25 patients with diabetes mellitus (DM) was 149 +/- 260 pg/ml. A trend towards an increase in sCLEC-2 concentration in the DM patients may reflect in vivo platelet activation in the patients, suggesting that sCLEC-2 may have clinical significance as a biomarker of in vivo platelet activation.

Hot water extracts of the medicinal mushroom Agaricus brasiliensis were investigated for their inhibition of platelet aggregation. The extracts significantly inhibited human platelet aggregation induced by adenosine 5'-diphosphate (ADP), but not by collagen or thrombin receptor-activating peptide. The extracts also had a significant inhibitory effect on shape change and intracellular calcium mobilization induced by ADP via inhibition of ADP binding to the P2Y(1) receptor. In addition, oral administration of the extracts resulted in prolonged tail bleeding time in mice. The marked antiplatelet activity of the mushroom extracts involving the P2Y(1) receptor suggests their potential therapeutic use against vascular disorders.

Although the global prevalence of both the overweight and obese is on the rise, there are variations among regions or countries, and sexes. Approximately half or more than half of the population are overweight/obese defined as body mass index >= 25 kg/m(2) in the Americas (61.1%), Europe (54.8%), and Eastern Mediterranean (46.0%) according to the World Health Organization, while a much lower prevalence is observed in Africa (26.9%), South-East Asia (13.7%), and the Western Pacific (25.4%). Females are more likely to be overweight/obese in the Eastern Mediterranean, Africa, South-East Asia and the majority of countries in the Americas and Western Pacific but not in the most of the countries in Europe. These region-sex-ethnicity differences in prevalence may be a clue to the causes of the obesity epidemic. Epidemiological studies done in the USA, Europe, and Asia found that higher BMI was significantly associated with increased incidence of coronary artery disease (CAD) and ischemic stroke, but the association with hemorrhagic stroke incidence was not always consistent. The association of BMI with CAD and ischemic stroke was generally independent of known mediators, which would indicate the importance of controlling or preventing overweight/obesity for the prevention of cardiovascular disease.

Background: The additive value of plaque characteristics determined by computed tomography angiography (CTA) in patients undergoing invasive coronary angiography (ICA) has not been established. Methods and Results: We studied 676 patients undergoing ICA and CTA within 3 months. The luminal diameter narrowing based on ICA and the presence of high risk plaque (HAP) based on CTA were assessed in all coronary artery segments except for those after or before scheduled treatment. We followed their cardiac events including cardiac death, acute coronary syndrome (ACS), and revascularization for de novo lesions months after ICA. The incidence of coronary events was higher in the segments including >25% luminal narrowing than in those without (2.94% vs. 0.31%, P<0.0001), and higher in the segments containing HAP than in those without (12.6 vs. 0.46%, P<0.0001). Greater than 25% residual luminal narrowing and the presence of HAP were identified as independent predictors of cardiac events after risk adjustment for age, gender, and history of ACS (hazard ratio [HR], 3.22; 95% confidence interval [Cl]: 1.29-10.76; P=0.0092, HR, 2.64; 95% Cl: 1.59-4.35; P=0.0002, respectively). Adding the presence of HAP to a model including age, gender, ACS history, and >25% residual stenosis improved the prediction of cardiac events. Conclusions: Assessment of coronary plaque characteristics on CTA improves the prediction of cardiac events in patients undergoing ICA.

The Annual Congress of the European Society of Cardiology (ESC) was held in Barcelona from 30th August to 3rd September 2014. More than 30,300 attendees from around the world shared the latest original research, including 27 clinical Hot Line studies, 12 basic science Hot Lines, 15 clinical trial updates, 19 registry studies, and 4,597 abstracts. Many important issues were presented, including novel treatment strategies for heart failure, acute coronary syndrome, interventional treatment for structural heart disease, renal denervation, novel anticoagulant therapies, atrial fibrillation and so on. In addition, 5 new ESC clinical practice guidelines (ie, myocardial revascularization, non-cardiac surgery, acute pulmonary embolism, hypertrophic cardiomyopathy, and aortic disease) were launched. It should be noted that Japan has recently been ranked in the top position in terms of the number of abstract submissions. Based on these activities, the ESC Congress has been recognized as the dominant scientific and educational forum for healthcare professionals in cardiology. We report the highlights and several key presentations of the ESC Congress 2014. The scientific activities and growing contributions of Japanese cardiologists or cardiovascular surgeons enhance the favorable relationship between the ESC and the Japanese Circulation Society.

The origin of a spontaneous triploid asparagus plant from crosses of 2x x 2x was investigated by SSR and flow cytometric analyses. One hundred and twenty-four progeny were obtained from crosses between a diploid female 'Gold Schatz' and a diploid male 'Hokkai 100'. SSR analysis proved that two and one genes were transmitted from the maternal and paternal parents, respectively, at each SSR locus of one progeny, 07M-61, whereas one gene each was from the female and male parents in the other diploid progeny. Triploidy of 07M-61 was confirmed by flow cytometric analysis. It was suggested that the triploid plant was derived from fertilization between an unreduced egg and reduced sperm nuclei, given its SSR genotypes. It was also suggested that the unreduced maternal gamete was derived from first division restitution (FDR) or second division restitution (SDR) with chiasma occurrence during meiosis. There were no noticeable morphological differences between the triploid and diploid progeny.

Thrombosis is a common pathology underlying ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). The Global Burden of Disease Study 2010 (GBD 2010) documented that ischemic heart disease and stroke collectively caused one in four deaths worldwide. GBD 2010 did not report data for VTE as a cause of death and disability. We performed a systematic review of the literature on the global disease burden due to VTE in low-, middle-, and high-income countries. Studies from Western Europe, North America, Australia, and Southern Latin America (Argentina) yielded consistent results with annual incidences ranging from 0.75 to 2.69 per 1,000 individuals in the population. The incidence increased to between 2 and 7 per 1,000 among those 70 years of age or more. Although the incidence is lower in individuals of Chinese and Korean ethnicity, their disease burden is not low because of population aging. VTE associated with hospitalization was the leading cause of disability-adjusted-life-years (DALYs) lost in low- and middle-income countries, and second in high-income countries, responsible for more DALYs lost than nosocomial pneumonia, catheter-related blood stream infections, and adverse drug events. VTE causes a major burden of disease across low-, middle-, and high-income countries. More detailed data on the global burden of VTE should be obtained to inform policy and resource allocation in health systems, and to evaluate if improved utilization of preventive measures will reduce the burden.

It is implicated that diabetic patients are more resistant to aspirin therapy than patients with other diseases or healthy individuals. We evaluated the inhibitory effects of aspirin on aggregation and the cyclooxygenase activity of platelets of 10 patients with severe type-2 diabetes mellitis (DM) and compared the results with those of healthy individuals. Although platelet aggregation had a tendency to be more resistant to aspirin with the DM group, there was no significant difference in half maximal inhibitory concentration 50 values of aspirin on the cyclooxygenase activity between the patients with DM and healthy individuals. Thus, the residual platelet aggregability uninhibited by aspirin appears to be independent of the cyclooxygenase activity. Since adenosine diphosphate (ADP) receptor blocking almost completely inhibited the residual platelet aggregability, it is suggested that hyperreactivity to ADP is more prevalent in patients with DM.

Background: The migration of T cell to atherosclerotic lesions is proposed to be involved in the pathogenesis of the atherosclerosis. Sphingosine 1-phosphate (S1P), a bioactive lysophospholipid released from activated platelets, exerts a variety of responses such as cell migration and proliferation, and reportedly induces T cell migration. Accordingly, platelet-T cell interactions may exist based on T cell responses triggered by platelet-derived S1P. Methods: S1P was measured using two-step lipid extraction followed by high-performance liquid chromatography (HPLC) separation while other phospholipids were determined by an enzymatic assay. The expression of S1P and lysophosphatidic acid receptors on Jurkat T cells was examined by RT-PCR and flow cytometry. Jurkat cell migration by S1P and the supernatant of activated platelets (SAP) was evaluated by a modified Boyden's chamber assay. Results: S1P(1) receptor was confirmed to be expressed on Jurkat T cell by RT-PCR and flow cytometry. S1P at 10-100 nM induced strong Jurkat cell migration, which was inhibited by the S1P(1) (and S1P(3)) antagonist VPC23019 and the Gi inactivator pertussis toxin (PTX). We found that the supernatant (releasate) of human platelets activated by collagen stimulation, which contains S1P abundantly, induced Jurkat cell migration and that the migration was inhibited by VPC23019 and PTX. In addition, human serum, into which platelet contents (including S1P) are fully released, induced the Jurkat cell migration, which was also inhibited by VPC23019. Conclusions: Our findings suggest that platelet-derived S1P induces Jurkat T cell migration possibly via S1P(1). S1P may be a key molecule involved in the responses triggered by platelet-T cell interactions, including atherosclerosis.

Platelets play an important role in various thrombotic diseases, including myocardial infarction. Because red wine consumption is inversely associated with death due to ischemic heart diseases, the effects of grape components on platelet function have been extensively investigated. Grape seed extracts (GSEs) reportedly inhibit platelet aggregation; however, the underlying mechanism has not been elucidated. We discovered that GSEs inhibit platelet aggregation induced by collagen and thrombin-receptor agonist peptide and increase basal levels of tyrosine phosphorylation, which was also observed in the presence of a protein tyrosine phosphatase (PTP) inhibitor. An in vitro phosphatase assay indicated that GSE dose dependently inhibited PTP-1B and Src homology 2 domain-containing phosphatase-1 activity, which positively regulates platelet aggregation. We propose that GSEs inhibit platelet aggregation by inhibiting tyrosine phosphatase activity. Moreover, we showed that GSE ingestion inhibited platelet aggregation in mice without enhancing tail bleeding, implying that GSE supplementation might be beneficial to prevention of thrombotic diseases.

Platelets play a pivotal role in atherothrombosis and the antiplatelet agents have been proved to be useful in preventing onset of acute clinical events including myocardial infarction and stroke. Increasing number of natural compounds has been identified to be potential antiplatelet agents. Here we report the antiplatelet effect of glaucocalyxin A (GLA), an ent-diterpenoid that we isolated and purified from the aerial parts of Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) Hara, and investigate the molecular mechanisms by which GLA inhibits platelet activation and thrombus formation. The effect of GLA on platelet activation was measured using platelets freshly isolated from peripheral blood of healthy donors. Results showed that pretreatment of human platelets with lower concentrations of GLA (0.01μg/ml, 0.1μg/ml) significantly inhibited platelet aggregation induced by collagen (P&lt 0.001) and CRP (P&lt 0.01), a synthetic GPVI ligand, but not by ADP and U46619. Accordingly, GLA inhibited collagen-stimulated tyrosine phosphorylation of Syk, LAT, and phospholipase Cγ2, the signaling events in collagen receptor GP? pathway. GLA also inhibited platelet p-selectin secretion and integrin activation by convulxin, a GPVI selective ligand. Additionally, GLA was found to inhibit low-dose thrombin-induced platelet activation. Using a flow chamber device, GLA was found to attenuate platelet adhesion on collagen surfaces in high shear condition. In vivo studies showed that GLA administration increased the time for complete occlusion upon vascular injury in mice, but did not extend tail-bleeding time when mice were administered with relatively lower doses of GLA. Therefore, the present results provide the molecular basis for the inhibition effect of GLA on platelet activation and its in vivo effect on thrombus formation, suggesting that GLA could potentially be developed as an antiplatelet and antithrombotic agent. © 2013 Li et al.

Platelets were activated under the infection with H. pylori in human and mice. We investigated the role of VacA, an exotoxin released by H. pylori in this context. Acid-activated VacA, but not heated VacA, induced platelet CD62P expression. However, VacA reacted with none of the alleged VacA receptors present on platelet membranes. We therefore analyzed VacA associated proteins obtained through VacA affinity chromatography, using MALDI-TOF-MS. Multimerin1 was detected in two consecutive experiments, as the binding protein for VacA. Plasmon resonance confirmed their binding, and dot blot analysis revealed that the peptide sequence AA 321-340 of multimerin 1 is the binding site for VacA. In conclusion, we propose a new interaction between multimerin1 and VacA , which may give another insight into H. pylori-induced platelet activations under H. pylori infection. © 2013 Satoh et al. licensee BioMed Central Ltd.