Platelets最新文献

{"title":"How can we use proteomics to learn more about platelets?","authors":"Joseph E Aslan","doi":"10.1080/09537104.2023.2217932","DOIUrl":"10.1080/09537104.2023.2217932","url":null,"abstract":"<p><p>Proteomics tools provide a powerful means to identify, detect, and quantify protein-related details in studies of platelet phenotype and function. Here, we consider how historical and recent advances in proteomics approaches have informed our understanding of platelet biology, and, how proteomics tools can be used going forward to advance studies of platelets. It is now apparent that the platelet proteome is comprised of thousands of different proteins, where specific changes in platelet protein systems can accompany alterations in platelet function in health and disease. Going forward, many challenges remain in how to best carry out, validate and interpret platelet proteomics experiments. Future studies of platelet protein post-translational modifications such as glycosylation, or studies that take advantage of single cell proteomics and top-down proteomics methods all represent areas of interest to profiling and more richly understanding platelets in human wellness and disease.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2217932"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9907532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic background of thrombocytosis in mice mimicking hereditary thrombocytosis in humans.","authors":"Hiroyuki Kimura, Masahiro Onozawa, Takanori Teshima","doi":"10.1080/09537104.2023.2276697","DOIUrl":"10.1080/09537104.2023.2276697","url":null,"abstract":"","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2276697"},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71522413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet-derived mitochondria transfer facilitates wound-closure by modulating ROS levels in dermal fibroblasts.","authors":"Soomin Kim,&nbsp;Yujin Kim,&nbsp;Shin-Hye Yu,&nbsp;Seo-Eun Lee,&nbsp;Jong Hyeok Park,&nbsp;Gayoung Cho,&nbsp;Chul Choi,&nbsp;Kyuboem Han,&nbsp;Chun-Hyung Kim,&nbsp;Young Cheol Kang","doi":"10.1080/09537104.2022.2151996","DOIUrl":"https://doi.org/10.1080/09537104.2022.2151996","url":null,"abstract":"<p><p>Platelets are known to improve the wound-repair capacity of mesenchymal stem cells (MSCs) by transferring mitochondria intercellularly. This study aimed to investigate whether direct transfer of mitochondria (pl-MT) isolated from platelets could enhance wound healing <i>in vitro</i> using a cell-based model. Wound repairs were assessed by 2D gap closure experiment in wound scratch assay using human dermal fibroblasts (hDFs). Results demonstrated that pl-MT were successfully internalized into hDFs. It increased cell proliferation and promoted the closure of wound gap. Importantly, pl-MT suppressed both intracellular and mitochondrial ROS production induced by hydrogen peroxide, cisplatin, and TGF-β in hDFs. Taken together, these results suggest that pl-MT transfer might be used as a potential therapeutic strategy for wound repair.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2151996"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9564190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Src but not Syk causes weak reversal of GPVI-mediated platelet aggregation measured by light transmission aggregometry.","authors":"Hilaire Yam Fung Cheung,&nbsp;Luis A Moran,&nbsp;Albert Sickmann,&nbsp;Johan W M Heemskerk,&nbsp;Ángel Garcia,&nbsp;Steve P Watson","doi":"10.1080/09537104.2022.2069235","DOIUrl":"https://doi.org/10.1080/09537104.2022.2069235","url":null,"abstract":"<p><p>Src tyrosine kinases and spleen tyrosine kinase (Syk) have recently been shown to contribute to sustained platelet aggregation on collagen under arterial shear. In the present study, we have investigated whether Src and Syk are required for aggregation under minimal shear following activation of glycoprotein VI (GPVI) and have extended this to C-type lectin-like receptor-2 (CLEC-2) which signals through the same pathway. Aggregation was induced by the GPVI ligand collagen-related peptide (CRP) and the CLEC-2 ligand rhodocytin and monitored by light transmission aggregometry (LTA). Aggregation and tyrosine phosphorylation by both receptors were sustained for up to 50 min. The addition of inhibitors of Src, Syk or Bruton's tyrosine kinase (Btk) at 150 sec, by which time aggregation was maximal, induced rapid loss of tyrosine phosphorylation of their downstream proteins, but only Src kinase inhibition caused a weak (~10%) reversal in light transmission. A similar effect was observed when the inhibitors were combined with apyrase and indomethacin or glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist, eptifibatide. On the other hand, activation of GPIIb-IIIa by GPVI in a diluted platelet suspension, as measured by binding of fluorescein isothiocyanate-labeled antibody specific for the activated GPIIb-IIIa (FITC-PAC1), was reversed on the addition of Src and Syk inhibitors showing that integrin activation is rapidly reversible in the absence of outside-in signals. The results demonstrate that Src but not Syk and Btk contribute to sustained aggregation as monitored by LTA, possibly as a result of inhibition of outside-in signaling from GPIIb-IIIa to the cytoskeleton through a Syk-independent pathway. This is in contrast to the role of Syk in supporting sustained aggregation on collagen under arterial shear.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 8","pages":"1293-1300"},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10841366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate immune TLR7 signaling mediates platelet activation and platelet-leukocyte aggregate formation in murine bacterial sepsis.","authors":"Brittney Williams,&nbsp;Jing Zhu,&nbsp;Lin Zou,&nbsp;Wei Chao","doi":"10.1080/09537104.2022.2107627","DOIUrl":"https://doi.org/10.1080/09537104.2022.2107627","url":null,"abstract":"<p><p>Thrombocytopenia is a common complication in sepsis and is associated with higher mortality. Activated platelets express CD62P, which facilitates platelet-leukocyte aggregate (PLA) formation and contributes to thrombocytopenia in sepsis. We have reported that thrombocytopenia in murine sepsis is partly attributable to TLR7 signaling, but the underlying mechanism is unclear. In the current study, we tested the hypothesis that TLR7 mediates platelet activation and PLA formation during sepsis. In vitro, whole blood from WT mice treated with loxoribine, a TLR7 agonist, exhibited a dose-dependent increase in activated platelets compared to the control (PBS with 0.05% DMSO) or loxoribine-treated TLR7^-/- whole blood. In a murine model of sepsis, there was a significant increase in platelet activation and PLA formation 24 hours after cecal ligation and puncture (CLP) as evidenced by double positive expression of CD41⁺/CD62P⁺ and CD45⁺/CD62P⁺, respectively. The sepsis-induced PLA formation was significantly attenuated in TLR7^-/- mice. Finally, in ex-vivo experiments, plasma isolated from septic mice induced WT platelet activation, but such effect was significantly attenuated in platelets deficient of TLR7. These findings demonstrate a pivotal role of TLR7 signaling in platelet activation and PLA formation during bacterial sepsis.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 8","pages":"1251-1259"},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9833650/pdf/nihms-1860245.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10521674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet inhibition by low-dose aspirin is not influenced by body mass or weight.","authors":"Sean P Heffron, Joseph Windheim, Tessa J Barrett, Deepak Voora, Jeffrey S Berger","doi":"10.1080/09537104.2022.2087868","DOIUrl":"10.1080/09537104.2022.2087868","url":null,"abstract":"<p><p>Aspirin's clinical efficacy may be influenced by body weight and mass. Although inadequate platelet inhibition by aspirin is suggested as responsible, evidence for this in non-diabetic patients is sparse. We investigated the influence of body weight and mass on aspirin's inhibition of platelet aggregation in healthy adults without diabetes. Cohort one (NYU, n = 84) had light transmission aggregometry (LTA) of platelet-rich plasma to submaximal adenosine diphosphate (ADP) and arachidonic acid (AA) before and following 1 week of daily 81 mg non-enteric coated aspirin. Subjects in the validation cohort (Duke, n = 66) were randomized to 81 mg or 325 mg non-enteric coated aspirin for 4 weeks, immediately followed by 4 weeks of the other dose, with LTA to submaximal collagen, ADP, and AA before and after each dosage period. Body mass index (BMI) range was 18.0-57.5 kg/m² and 25% were obese. Inhibition of platelet aggregation was similar irrespective of BMI, body weight and aspirin dose. There was no correlation between platelet aggregation before or after aspirin with BMI or body weight. Our data demonstrate that aspirin produces potent inhibition of direct and indirect COX1-mediated platelet aggregation in healthy adults without diabetes regardless of body weight or mass - suggesting that other mechanisms explain lower preventive efficacy of low-dose aspirin with increasing body weight/mass.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 8","pages":"1208-1213"},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9976777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9359542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet-leukocyte aggregate formation and inflammation in patients with pulmonary arterial hypertension and CTEPH.","authors":"Mikael Åberg,&nbsp;Erik Björklund,&nbsp;Gerhard Wikström,&nbsp;Christina Christersson","doi":"10.1080/09537104.2022.2087867","DOIUrl":"https://doi.org/10.1080/09537104.2022.2087867","url":null,"abstract":"<p><p>Pulmonary hypertension (PH) is defined by increased mean pulmonary artery pressure, and the clinical classification includes five etiologies, of which we investigated subgroup 1, pulmonary arterial hypertension (PAH) and subgroup 4, chronic thrombotic and/or embolic disease (CTEPH). Platelets participate in both innate and adaptive immune responses and could possibly contribute to the suggested systemic inflammation associated with PAH. In this study, we utilized flow cytometry to analyze platelet activation and platelet-monocyte (PMA) and granulocyte (PGA) aggregates in PAH and CTEPH patients and healthy control subjects. The plasma concentration of proinflammatory cytokines was measured by multiplex electrochemiluminescence. Our main finding is that circulating platelets are activated in the circulation and form aggregates with both monocytes and granulocytes in patients with idiopathic PAH (IPAH), associated PAH (APAH) and pulmonary hypertension due to CTEPH. There was a strong correlation between the platelet activation, assessed as P-selectin, and the number of aggregates formed. IL-6, IL-8, IL-10 and TNF-α were increased in all PH subgroups as compared to healthy controls, and PMAs were associated with circulating IL-6, IL-8 and IL-10, whereas PGAs were associated with IL-6. The increased concentrations of platelet-leukocyte aggregates found in PAH/CTEPH patients might thus contribute to the inflammatory state in PH.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 8","pages":"1199-1207"},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10445194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence for a PI3-kinase independent pathway in the regulation of Rap1b activation downstream of the P2Y12 receptor in platelets.","authors":"Carol Dangelmaier, Satya P Kunapuli","doi":"10.1080/09537104.2022.2071855","DOIUrl":"10.1080/09537104.2022.2071855","url":null,"abstract":"<p><p>Platelet activation by adenosine diphosphate (ADP) is mediated through two G-protein-coupled receptors, P2Y1 and P2Y12, which signal through Gq and Gi, respectively. P2Y1 stimulation leads to phospholipase C activation and an increase in cytosolic calcium necessary for CalDAG-GEF1 activation. Engagement of P2Y12 inhibits adenylate cyclase, which reduces cAMP, and activation of PI3-kinase, which inhibits RASA3 resulting in sustained activated Rap1b. In this study we activated human platelets with 2-MeSADP in the presence of LY294002, a PI3-kinase inhibitor, AR-C69931MX, a P2Y12 antagonist or MRS2179, a P2Y1 antagonist. We measured the phosphorylation of Akt on Ser473 as an indicator of PI3-kinase activity. As previously shown, LY294002 and ARC69931MX abolished 2MeSADP-induced Akt phosphorylation. MRS2179 reduced ADP-induced Akt phosphorylation but did not abolish it. Rap1b activation, however, was only reduced, but not ablated, using LY294002 and was completely inhibited by ARC69931MX or MRS2179. Furthermore, 2MeSADP-induced Rap1b activation was abolished in either P2Y1 or P2Y12 null platelets. These data suggest that ADP-induced Rap1b activation requires both P2Y1 and P2Y12. In addition, although stimulation of P2Y12 results in PI3-kinase activation leading to Akt phosphorylation and Rap1b activation, Rap1b activation can occur independently of PI3-kinase downstream of P2Y12. Thus, we propose that the P2Y12 receptor can regulate Rap1b, possibly through RASA3, in a pathway independent of PI3-kinase.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 1","pages":"1301-1306"},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43075825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Romiplostim for PARP inhibitor-induced thrombocytopenia in solid tumor malignancies.","authors":"Abraham Z Cheloff,&nbsp;Hanny Al-Samkari","doi":"10.1080/09537104.2022.2117293","DOIUrl":"https://doi.org/10.1080/09537104.2022.2117293","url":null,"abstract":"TO THE EDITOR: PARP (poly-adenosine diphosphate-ribose polymerase) inhibitors are a series of drugs designed to inhibit DNA repair mechanisms, preventing DNA repair in cancer cells and inducing cell death [1]. Currently approved for the treatment of breast, ovarian, pancreatic, and prostate cancers [2], indications for PARP inhibitor therapy continue to expand. However, patients undergoing PARP inhibitor treatment may encounter multiple hematologic toxicities, including anemia, neutropenia, and thrombocytopenia [3,4]. Based on recent results describing success in the use of romiplostim to treat chemotherapy-induced thrombocytopenia (CIT) in patients receiving traditional myelosuppressive chemotherapy [5–8] we sought to understand whether a similar approach could be used for PARP inhibitor induced thrombocytopenia, for which there are little published data. A case series of 5 patients with PARP inhibitor-induced thrombocytopenia treated with avatrombopag suggests potential effectiveness of thrombopoietin receptor agonists in these patients; however, no data to date has been published evaluating romiplostim for PARP inhibitorinduced thrombocytopenia. Given that none of these agents are FDAapproved for CIT but that the majority of safety and efficacy data for use of TPO-RAs to treat CIT generally is for romiplostim (thereby resulting in its specific inclusion as a treatment option for CIT in recent NCCN guidelines) [9,10], we sought to examine romiplostim use in patients with PARP inhibitor-induced thrombocytopenia. This study was approved by the Institutional Review Board of Mass General Brigham (protocol #2015P000152). An electronic patient data registry at Mass General Brigham was used to identify patients who had received both romiplostim and a PARP inhibitor (niraparib, olaparib, rucaparib, or talazoparib) at any time. This resource was used specifically to identify the study population; patients identified by the query then underwent manual chart review by the authors to determine which patients met inclusion criteria (defined as a patient diagnosed with cancer, prescribed a PARP inhibitor, who developed thrombocytopenia requiring support and was treated with romiplostim). Clinical data regarding patients’ oncologic treatment course, platelet counts, and any adverse events were collected manually from charts by investigators and analyzed. The database query returned 32 patients who met initial criteria (had received romiplostim and a PARP inhibitor). Manual review of each chart found 5 patients who met inclusion criteria, all of whom were prescribed niraparib. Baseline characteristics and parameters for these patients can be found in Table I. Platelet counts for each patient were collected prior to niraparib prescription (baseline platelet count), prior to romiplostim initiation, and during romiplostim therapy (on-romiplostim counts defined as platelet counts drawn one week after each romiplostim administration until one week after the last do","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 8","pages":"1312-1313"},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10690440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apolipoprotein A-I, elevated in trauma patients, inhibits platelet activation and decreases clot strength.","authors":"Wilbert L Jones, Christopher R Ramos, Anirban Banerjee, Ernest E Moore, Kirk C Hansen, Julia R Coleman, Marguerite Kelher, Keith B Neeves, Christopher C Silliman, Jorge Di Paola, Brian Branchford","doi":"10.1080/09537104.2022.2078488","DOIUrl":"10.1080/09537104.2022.2078488","url":null,"abstract":"<p><p>Apolipoprotein A-I (ApoA-I) is elevated in the plasma of a subgroup of trauma patients with systemic hyperfibrinolysis. We hypothesize that apoA-I inhibits platelet activation and clot formation. The effects of apoA-I on human platelet activation and clot formation were assessed by whole blood thrombelastography (TEG), platelet aggregometry, P-selectin surface expression, microfluidic adhesion, and Akt phosphorylation. Mouse models of carotid artery thrombosis and pulmonary embolism were used to assess the effects of apoA-I <i>in vivo</i>. The ApoA-1 receptor was investigated with transgenic mice knockouts (KO) for the scavenger receptor class B member 1 (SR-BI). Compared to controls, exogenous human apoA-I inhibited arachidonic acid and collagen-mediated human and mouse platelet aggregation, decreased P-selectin surface expression and Akt activation, resulting in diminished clot strength and increased clot lysis by TEG. ApoA-I also decreased platelet aggregate size formed on a collagen surface under flow. <i>In vivo</i>, apoA-I delayed vessel occlusion in an arterial thrombosis model and conferred a survival advantage in a pulmonary embolism model. SR-BI KO mice significantly reduced apoA-I inhibition of platelet aggregation versus wild-type platelets. Exogenous human apoA-I inhibits platelet activation, decreases clot strength and stability, and protects mice from arterial and venous thrombosis via the SR-BI receptor.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"33 1","pages":"1119-1131"},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46109440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}