Platelets最新文献_第9页

The prospects of microphysiological systems in modeling platelet pathophysiology in cancer. 微生理系统在模拟肿瘤血小板病理生理中的应用前景。

IF 2.5 3区医学

Platelets Pub Date : 2023-12-01 DOI: 10.1080/09537104.2023.2247489

Lopamudra D Ghosh, Abhishek Jain

{"title":"The prospects of microphysiological systems in modeling platelet pathophysiology in cancer.","authors":"Lopamudra D Ghosh, Abhishek Jain","doi":"10.1080/09537104.2023.2247489","DOIUrl":"10.1080/09537104.2023.2247489","url":null,"abstract":"The contribution of platelets is well recognized in thrombosis and hemostasis. However, platelets also promote tumor progression and metastasis through their crosstalk with various cells of the tumor microenvironment (TME). For example, several cancer models continue to show that platelet functions are readily altered by cancer cells upon activation leading to the formation of platelet-tumor aggregates, triggering release of soluble factors from platelet granules and altering platelet turnover. Further, activated platelets protect tumor cells from shear forces in circulation and assault of cytotoxic natural killer (NK) cells. Platelet-secreted factors promote proliferation of malignant cells, metastasis, and chemoresistance. Much of our knowledge of platelet biology in cancer has been achieved with animal models, particularly murine. However, this preclinical understanding of the complex pathophysiology is yet to be fully realized and translated to clinical trials in terms of new approaches to treat cancer via controlling the platelet function. In this review, we summarize the current state of knowledge of platelet physiology obtained through existing in vivo and in vitro cancer models, the complex interactions of platelets with cancer cells in TME and the pathways by which platelets may confer chemoresistance. Since the FDA Modernization Act recently passed by the US government has made animal models optional in drug approvals, we critically examine the existing and futuristic value of employing bioengineered microphysiological systems and organ-chips to understand the mechanistic role of platelets in cancer metastasis and exploring novel therapeutic targets for cancer prevention and treatment.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2247489"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10578702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10115353","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}

引用次数: 0

Deep learning, 3D ultrastructural analysis reveals quantitative differences in platelet and organelle packing in COVID-19/SARSCoV2 patient-derived platelets. 深度学习、3D超微结构分析揭示了新冠肺炎/SARSCoV2患者衍生血小板中血小板和细胞器包装的定量差异。

IF 2.5 3区医学

Platelets Pub Date : 2023-12-01 Epub Date: 2023-11-07 DOI: 10.1080/09537104.2023.2264978

Sagar S Matharu, Cassidy S Nordmann, Kurtis R Ottman, Rahul Akkem, Douglas Palumbo, Denzel R D Cruz, Kenneth Campbell, Gail Sievert, Jamie Sturgill, James Z Porterfield, Smita Joshi, Hammodah R Alfar, Chi Peng, Irina D Pokrovskaya, Jeffrey A Kamykowski, Jeremy P Wood, Beth Garvy, Maria A Aronova, Sidney W Whiteheart, Richard D Leapman, Brian Storrie

{"title":"Deep learning, 3D ultrastructural analysis reveals quantitative differences in platelet and organelle packing in COVID-19/SARSCoV2 patient-derived platelets.","authors":"Sagar S Matharu, Cassidy S Nordmann, Kurtis R Ottman, Rahul Akkem, Douglas Palumbo, Denzel R D Cruz, Kenneth Campbell, Gail Sievert, Jamie Sturgill, James Z Porterfield, Smita Joshi, Hammodah R Alfar, Chi Peng, Irina D Pokrovskaya, Jeffrey A Kamykowski, Jeremy P Wood, Beth Garvy, Maria A Aronova, Sidney W Whiteheart, Richard D Leapman, Brian Storrie","doi":"10.1080/09537104.2023.2264978","DOIUrl":"10.1080/09537104.2023.2264978","url":null,"abstract":"Platelets contribute to COVID-19 clinical manifestations, of which microclotting in the pulmonary vasculature has been a prominent symptom. To investigate the potential diagnostic contributions of overall platelet morphology and their α-granules and mitochondria to the understanding of platelet hyperactivation and micro-clotting, we undertook a 3D ultrastructural approach. Because differences might be small, we used the high-contrast, high-resolution technique of focused ion beam scanning EM (FIB-SEM) and employed deep learning computational methods to evaluate nearly 600 individual platelets and 30 000 included organelles within three healthy controls and three severely ill COVID-19 patients. Statistical analysis reveals that the α-granule/mitochondrion-to-plateletvolume ratio is significantly greater in COVID-19 patient platelets indicating a denser packing of organelles, and a more compact platelet. The COVID-19 patient platelets were significantly smaller -by 35% in volume - with most of the difference in organelle packing density being due to decreased platelet size. There was little to no 3D ultrastructural evidence for differential activation of the platelets from COVID-19 patients. Though limited by sample size, our studies suggest that factors outside of the platelets themselves are likely responsible for COVID-19 complications. Our studies show how deep learning 3D methodology can become the gold standard for 3D ultrastructural studies of platelets.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2264978"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10809228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71485175","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}

引用次数: 0

Cryopreservation affects platelet macromolecular composition over time after thawing and differently impacts on cancer cells behavior in vitro. 低温保存对解冻后血小板大分子组成的影响以及对体外癌细胞行为的不同影响。

IF 3.3 3区医学

Platelets Pub Date : 2023-12-01 Epub Date: 2023-11-27 DOI: 10.1080/09537104.2023.2281943

Gaia Gavioli, Agnese Razzoli, Diana E Bedolla, Erminia Di Bartolomeo, Eleonora Quartieri, Barbara Iotti, Pamela Berni, Giovanni Birarda, Lisa Vaccari, Davide Schiroli, Chiara Marraccini, Roberto Baricchi, Lucia Merolle

{"title":"Cryopreservation affects platelet macromolecular composition over time after thawing and differently impacts on cancer cells behavior in vitro.","authors":"Gaia Gavioli, Agnese Razzoli, Diana E Bedolla, Erminia Di Bartolomeo, Eleonora Quartieri, Barbara Iotti, Pamela Berni, Giovanni Birarda, Lisa Vaccari, Davide Schiroli, Chiara Marraccini, Roberto Baricchi, Lucia Merolle","doi":"10.1080/09537104.2023.2281943","DOIUrl":"10.1080/09537104.2023.2281943","url":null,"abstract":"Cryopreservation affects platelets' function, questioning their use for cancer patients. We aimed to investigate the biochemical events that occur over time after thawing to optimize transfusion timing and evaluate the effect of platelet supernatants on tumor cell behavior in vitro. We compared fresh (Fresh-PLT) with Cryopreserved platelets (Cryo-PLT) at 1 h, 3 h and 6 h after thawing. MCF-7 and HL-60 cells were cultured with Fresh- or 1 h Cryo-PLT supernatants to investigate cell proliferation, migration, and PLT-cell adhesion. We noticed a significant impairment of hemostatic activity accompanied by a post-thaw decrease of CD42b+ , which identifies the CD62P--population. FTIR spectroscopy revealed a decrease in the total protein content together with changes in their conformational structure, which identified two sub-groups: 1) Fresh and 1 h Cryo-PLT; 2) 3 h and 6 h cryo-PLT. Extracellular vesicle shedding and phosphatidylserine externalization (PS) increased after thawing. Cryo-PLT supernatants inhibited cell proliferation, impaired MCF-7 cell migration, and reduced ability to adhere to tumor cells. Within the first 3 hours after thawing, irreversible alterations of biomolecular structure occur in Cryo-PLT. Nevertheless, Cryo-PLT should be considered safe for the transfusion of cancer patients because of their insufficient capability to promote cancer cell proliferation, adhesion, or migration.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2281943"},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138445979","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}

引用次数: 0

Multiple myeloma and its treatment contribute to increased platelet reactivity. 多发性骨髓瘤及其治疗有助于提高血小板反应性。

IF 3.3 3区医学

Platelets Pub Date : 2023-12-01 Epub Date: 2023-10-11 DOI: 10.1080/09537104.2023.2264940

Joanne L Mitchell, Dalia Khan, Rekha H Rana, Neline Kriek, Amanda J Unsworth, Tanya Sage, Alexander P Bye, Michael Laffan, Susan Shapiro, Anjan Thakurta, Henri Grech, Karthik Ramasamy, Jonathan M Gibbins

{"title":"Multiple myeloma and its treatment contribute to increased platelet reactivity.","authors":"Joanne L Mitchell, Dalia Khan, Rekha H Rana, Neline Kriek, Amanda J Unsworth, Tanya Sage, Alexander P Bye, Michael Laffan, Susan Shapiro, Anjan Thakurta, Henri Grech, Karthik Ramasamy, Jonathan M Gibbins","doi":"10.1080/09537104.2023.2264940","DOIUrl":"10.1080/09537104.2023.2264940","url":null,"abstract":"Multiple myeloma (MM) and its precursor states, smoldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with increased incidence of thrombosis, however the cause of this is unknown. Lenalidomide treatment of MM substantially improves patient survival, although significantly increases thrombotic risk by an unknown mechanism. This pilot study aimed to establish the impact of MM and its treatment with Lenalidomide on platelet function. We analyzed platelet function in MGUS, SM and MM compared to healthy controls. We report an increase in platelet reactivity in MGUS, SM, and MM where increases in fibrinogen binding, P-selectin exposure, altered receptor expression, elevated levels of aggregation and enhanced sensitivity to agonist stimulation were observed. We also demonstrate an increase in patient platelet reactivity post Lenalidomide treatment compared to pre-treatment. We show Lenalidomide treatment of platelets ex vivo increased reactivity that was associated with formation of larger thrombi at arterial shear rates but not venous shear rates. This study demonstrates a clear increase in platelet reactivity and prothrombotic potential in patients with MGUS, SM and MM which is elevated further upon treatment with Lenalidomide. Our observations suggest that more detailed studies are warranted to determine mechanisms of thrombotic complications to enable the development of new preventative strategies that specifically target platelets.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2264940"},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41210084","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}

引用次数: 0

High plasma soluble CLEC-2 level predicts oxygen therapy requirement in patients with COVID-19. 高血浆可溶性CLEC-2水平预测新冠肺炎患者的氧气治疗需求。

IF 3.3 3区医学

Platelets Pub Date : 2023-12-01 Epub Date: 2023-08-14 DOI: 10.1080/09537104.2023.2244594

Saori Oishi, Makyo Ueda, Hirokazu Yamazaki, Nagaharu Tsukiji, Toshiaki Shirai, Yuna Naito, Masumi Endo, Ryohei Yokomori, Tomoyuki Sasaki, Katsue Suzuki-Inoue

{"title":"High plasma soluble CLEC-2 level predicts oxygen therapy requirement in patients with COVID-19.","authors":"Saori Oishi, Makyo Ueda, Hirokazu Yamazaki, Nagaharu Tsukiji, Toshiaki Shirai, Yuna Naito, Masumi Endo, Ryohei Yokomori, Tomoyuki Sasaki, Katsue Suzuki-Inoue","doi":"10.1080/09537104.2023.2244594","DOIUrl":"10.1080/09537104.2023.2244594","url":null,"abstract":"Predicting the clinical course and allocating limited medical resources appropriately is crucial during the COVID-19 pandemic. Platelets are involved in microthrombosis, a critical pathogenesis of COVID-19; however, the role of soluble CLEC-2 (sCLEC-2), a novel platelet activation marker, in predicting the prognosis of COVID-19 remains unexplored. We enrolled 108 patients with COVID-19, hospitalized between January 2021 and May 2022, to evaluate the clinical use of sCLEC-2 as a predictive marker. sCLEC-2 levels were measured in plasma sampled on admission, as well as interleukin-6, cell-free DNA, von Willebrand factor, and thrombomodulin. We retrospectively classified the patients into two groups - those who required oxygenation during hospitalization (oxygenated group) and those who did not (unoxygenated group) - and compared their clinical and laboratory characteristics. The correlation between sCLEC-2 and the other parameters was validated. The sCLEC-2 level was significantly higher in the oxygenated group (188.8 pg/mL vs. 296.1 pg/mL). Multivariate analysis identified high sCLEC-2 levels (odds ratio per 10 pg/mL:1.25) as an independent predictor of oxygen therapy requirement. sCLEC-2 was positively correlated with cell-free DNA, supporting the association between platelet activation and neutrophil extracellular traps. In conclusion, sCLEC-2 is a clinically valuable marker in predicting oxygen therapy requirements for patients with COVID-19.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2244594"},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10044853","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}

引用次数: 0

Platelet glycogenolysis is important for energy production and function. 血小板糖原分解对能量的产生和功能至关重要。

IF 2.5 3区医学

Platelets Pub Date : 2023-12-01 DOI: 10.1080/09537104.2023.2222184

Kanakanagavalli Shravani Prakhya, Hemendra Vekaria, Daniёlle M Coenen, Linda Omali, Joshua Lykins, Smita Joshi, Hammodah R Alfar, Qing Jun Wang, Patrick Sullivan, Sidney W Whiteheart

{"title":"Platelet glycogenolysis is important for energy production and function.","authors":"Kanakanagavalli Shravani Prakhya, Hemendra Vekaria, Daniёlle M Coenen, Linda Omali, Joshua Lykins, Smita Joshi, Hammodah R Alfar, Qing Jun Wang, Patrick Sullivan, Sidney W Whiteheart","doi":"10.1080/09537104.2023.2222184","DOIUrl":"10.1080/09537104.2023.2222184","url":null,"abstract":"Although the presence of glycogen in platelets was established in the 1960s, its importance to specific functions (i.e., activation, secretion, aggregation, and clot contraction) remains unclear. Patients with glycogen storage disease often present with increased bleeding and glycogen phosphorylase (GP) inhibitors, when used as treatments for diabetes, induce bleeding in preclinical studies suggesting some role for this form of glucose in hemostasis. In the present work, we examined how glycogen mobilization affects platelet function using GP inhibitors (CP316819 and CP91149) and a battery of ex vivo assays. Blocking GP activity increased glycogen levels in resting and thrombin-activated platelets and inhibited platelet secretion and clot contraction, with minimal effects on aggregation. Seahorse energy flux analysis and metabolite supplementation experiments suggested that glycogen is an important metabolic fuel whose role is affected by platelet activation and the availability of external glucose and other metabolic fuels. Our data shed light on the bleeding diathesis in glycogen storage disease patients and offer insights into the potential effects of hyperglycemia on platelets.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2222184"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9609392","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}

引用次数: 0

Treatment inequity in antiplatelet therapy for ischaemic heart disease in patients with advanced chronic kidney disease: releasing the evidence vacuum. 晚期慢性肾脏病患者缺血性心脏病抗血小板治疗的不公平性：释放证据真空。

IF 2.5 3区医学

Platelets Pub Date : 2023-12-01 DOI: 10.1080/09537104.2022.2154330

Frances L Varian, William A E Parker, James Fotheringham, Robert F Storey

引用次数: 0

The CalDAG-GEFI/Rap1/αIIbβ3 axis minimally contributes to accelerated platelet clearance in mice with constitutive store-operated calcium entry. CalDAG-GEFI/Rap1/αIIbβ3轴对组成性储存操作钙进入小鼠血小板清除的加速作用最小。

IF 2.5 3区医学

Platelets Pub Date : 2023-12-01 DOI: 10.1080/09537104.2022.2157383

Robert H Lee, David J Rocco, Bernhard Nieswandt, Wolfgang Bergmeier

{"title":"The CalDAG-GEFI/Rap1/αIIbβ3 axis minimally contributes to accelerated platelet clearance in mice with constitutive store-operated calcium entry.","authors":"Robert H Lee, David J Rocco, Bernhard Nieswandt, Wolfgang Bergmeier","doi":"10.1080/09537104.2022.2157383","DOIUrl":"10.1080/09537104.2022.2157383","url":null,"abstract":"Circulating platelets maintain low cytosolic Ca2+ concentrations. At sites of vascular injury, agonist-induced Ca2+ release from platelet intracellular stores triggers influx of extracellular Ca2+, a process known as store-operated Ca2+ entry (SOCE). Stromal interaction molecule 1 (Stim1) senses reduced Ca2+ stores and triggers SOCE. Gain-of-function (GOF) mutations in Stim1, such as described for Stormorken syndrome patients or mutant mice (Stim1Sax), are associated with marked thrombocytopenia and increased platelet turnover. We hypothesized that reduced platelet survival in Stim1Sax/+ mice is due to increased Rap1/integrin signaling and platelet clearance in the spleen, similar to what we recently described for mice expressing a mutant version of the Rap1-GAP, Rasa3 (Rasa3hlb/hlb). Stim1Sax/+ mice were crossed with mice deficient in CalDAG-GEFI, a critical calcium-regulated Rap1-GEF in platelets. In contrast to Rasa3hlb/hlb x Caldaggef1-/- mice, only a small increase in the peripheral platelet count, but not platelet lifespan, was observed in Stim1Sax/+ x Caldaggef1-/- mice. Similarly, inhibition of αIIbβ3 integrin in vivo only minimally raised the peripheral platelet count in Stim1Sax/+ mice. Compared to controls, Stim1Sax/+ mice exhibited increased platelet accumulation in the lung, but not the spleen or liver. These results suggest that CalDAG-GEFI/Rap1/integrin signaling contributes only minimally to accelerated platelet turnover caused by constitutive SOCE.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2157383"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10032033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9152828","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}

引用次数: 0

The complementary roles of VAMP-2, -3, and -7 in platelet secretion and function. VAMP-2、-3和-7在血小板分泌和功能中的互补作用。

IF 2.5 3区医学

Platelets Pub Date : 2023-12-01 DOI: 10.1080/09537104.2023.2237114

Smita Joshi, Kanakanagavalli Shravani Prakhya, Alexis N Smith, Harry Chanzu, Ming Zhang, Sidney W Whiteheart

{"title":"The complementary roles of VAMP-2, -3, and -7 in platelet secretion and function.","authors":"Smita Joshi, Kanakanagavalli Shravani Prakhya, Alexis N Smith, Harry Chanzu, Ming Zhang, Sidney W Whiteheart","doi":"10.1080/09537104.2023.2237114","DOIUrl":"10.1080/09537104.2023.2237114","url":null,"abstract":"Platelet secretion requires Soluble N-ethylmaleimide Sensitive Attachment Protein Receptors (SNAREs). Vesicle SNAREs/Vesicle-Associated Membrane Proteins (v-SNAREs/VAMPs) on granules and t-SNAREs in plasma membranes mediate granule release. Platelet VAMP heterogeneity has complicated the assessment of how/if each is used and affects hemostasis. To address the importance of VAMP-7 (V7), we analyzed mice with global deletions of V3 and V7 together or platelet-specific deletions of V2, V3, and global deletion of V7. We measured the kinetics of cargo release, and its effects on three injury models to define the context-specific roles of these VAMPs. Loss of V7 minimally affected dense and α granule release but did affect lysosomal release. V3-/-7-/- and V2Δ3Δ7-/- platelets showed partial defects in α and lysosomal release; dense granule secretion was unaffected. In vivo assays showed that loss of V2, V3, and V7 caused no bleeding or occlusive thrombosis. These data indicate a role for V7 in lysosome release that is partially compensated by V3. V7 and V3, together, contribute to α granule release, however none of these deletions affected hemostasis/thrombosis. Our results confirm the dominance of V8. When it is present, deletion of V2, V3, or V7 alone or in combination minimally affects platelet secretion and hemostasis.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2237114"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10564522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41210085","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}

引用次数: 0

α-Synuclein is the major platelet isoform but is dispensable for activation, secretion, and thrombosis. α-突触核蛋白是主要的血小板同种型，但对活化、分泌和血栓形成是可有可无的。

IF 2.5 3区医学

Platelets Pub Date : 2023-12-01 Epub Date: 2023-11-05 DOI: 10.1080/09537104.2023.2267147

Alexis N Smith, Smita Joshi, Harry Chanzu, Hammodah R Alfar, Kanakanagavalli Shravani Prakhya, Sidney W Whiteheart

{"title":"α-Synuclein is the major platelet isoform but is dispensable for activation, secretion, and thrombosis.","authors":"Alexis N Smith, Smita Joshi, Harry Chanzu, Hammodah R Alfar, Kanakanagavalli Shravani Prakhya, Sidney W Whiteheart","doi":"10.1080/09537104.2023.2267147","DOIUrl":"10.1080/09537104.2023.2267147","url":null,"abstract":"Platelets play many roles in the vasculature ensuring proper hemostasis and maintaining integrity. These roles are facilitated, in part, by cargo molecules released from platelet granules via Soluble NSF Attachment Protein Receptor (SNARE) mediated membrane fusion, which is controlled by several protein-protein interactions. Chaperones have been characterized for t-SNAREs (i.e. Munc18b for Syntaxin-11), but none have been clearly identified for v-SNAREs. α-Synuclein has been proposed as a v-SNARE chaperone which may affect SNARE-complex assembly, fusion pore opening, and thus secretion. Despite its abundance and that it is the only isoform present, α-synuclein's role in platelet secretion is uncharacterized. In this study, immunofluorescence showed that α-synuclein was present on punctate structures that co-stained with markers for α-granules and lysosomes and in a cytoplasmic pool. We analyzed the phenotype of α-synuclein-/- mice and their platelets. Platelets from knockout mice had a mild, agonist-dependent secretion defect but aggregation and spreading in vitro were unaffected. Consistently, thrombosis/hemostasis were unaffected in the tail-bleeding, FeCl3 carotid injury and jugular vein puncture models. None of the platelet secretory machinery examined, e.g. the v-SNAREs, were affected by α-synuclein's loss. The results indicate that, despite its abundance, α-synuclein has only a limited role in platelet function and thrombosis.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2267147"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71485176","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}

引用次数: 0