Review
Biochemistry & Molecular Biology
Jinmi Zou, Frauke Swieringa, Bas de Laat, Philip G. de Groot, Mark Roest, Johan W. M. Heemskerk
Summary: This paper reviews the functional reversibility of integrin alpha IIb beta 3 activation and transient aggregation and discusses the signaling pathways involved. The study finds that ADP P2Y(1) and P2Y(12) receptor signaling via phosphoinositide 3-kinases and Akt are the principal pathways linked to reversible integrin activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Huong T. T. Nguyen, Zhen Xu, Xiaofeng Shi, Shuzhen Liu, Marie L. Schulte, Gilbert C. White, Yan-Qing Ma
Summary: The study identified a previously unrecognized paxillin binding site in the PH domain of kindlin-3, which plays an important role in supporting integrin alpha IIb beta 3 outside-in signaling in platelets. Disruption of paxillin binding inhibited platelet spreading on immobilized fibrinogen, while treatment with a specific membrane-permeable peptide derived from the PH domain of kindlin-3 reduced thrombus formation in mice. These findings highlight a novel antithrombotic target involving the interaction between paxillin and the PH domain of kindlin-3.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Natalie J. J. Jooss, Yvonne M. C. Henskens, Steve P. P. Watson, Richard W. W. Farndale, Meinrad P. P. Gawaz, Martine Jandrot-Perrus, Natalie S. S. Poulter, Johan W. M. Heemskerk
Summary: In this study, four inhibitors of platelet-collagen interactions were compared for their antithrombotic potential. The results showed that Revacept and 9O12-Fab had strong inhibitory effects on highly GPVI-activating surfaces, while 9O12-Fab had varying inhibitory effects on all surfaces. The effects of GPVI-directed interventions were surpassed by Syk inhibition, and 6F1 mAb had the strongest intervention effect on collagen substrates compared to Revacept and 9O12-Fab. These findings reveal the unique pharmacological profiles of these drugs and provide insights into additive antithrombotic mechanisms.
THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Biochemistry & Molecular Biology
Dan Shu, Ying Zhu, Meng Lu, Ao-Di He, Jiang-Bin Chen, Ding-Song Ye, Yue Liu, Xiang-Bin Zeng, Rong Ma, Zhang-Yin Ming
Summary: Sanguinarine demonstrates antiplatelet activity by inhibiting thrombus formation and platelet activation through multiple molecular mechanisms. This indicates its potential clinical value in treating cardiovascular diseases involving excessive platelet activation.
Article
Physiology
Ekaterina K. Selivanova, Dina K. Gaynullina, Olga S. Tarasova
Summary: Hyperthyroidism is associated with a decreased peripheral vascular resistance, potentially due to the vasodilator effects of thyroid hormones (TH). Non-genomic effects of TH on rat skeletal muscle arteries include T3-dependent endothelium-dependent relaxation and T4-dependent endothelium-independent relaxation. T4 exerts a stronger effect on alpha(1)-adrenergic contraction compared to T3, involving suppression of extracellular matrix signaling via integrin alpha v beta 3, ERK1/2, and ILK with subsequent decrease of MLC2 (Ser19) phosphorylation.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Hematology
Emily Janus-Bell, Alexandra Yakusheva, Cyril Scandola, Nicolas Receveur, Usman Muhammad Ahmed, Clarisse Mouriaux, Catherine Bourdon, Cecile Loubiere, Anita Eckly, Yotis A. Senis, Mikhail A. Panteleev, Christian Gachet, Pierre H. Mangin
Summary: The study demonstrates that platelet integrin alpha 5 beta 1 plays a key role in fibrillar cellular fibronectin, but is dispensable in hemostasis and arterial thrombosis.
THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Biotechnology & Applied Microbiology
Lijun Zhong, Lin Tang, Xiaoxia He
Summary: It has been discovered that ANGPTL3 plays an oncogenic role in several types of human malignancies. This study found that ANGPTL3 is highly expressed in cervical cancer cells and silencing ANGPTL3 can inhibit cell proliferation, migration, invasion, and angiogenesis. The inhibitory effect of ANGPTL3 can be offset by upregulating the expression of alpha v beta 3, which also promotes blood vessel formation and the secretion of VEGF and VEGFR2 in cervical cancer cells.
Article
Oncology
Mark Sutherland, Andrew Gordon, Fatemah O. F. O. Al-Shammari, Adam Throup, Amy Cilia La Corte, Helen Philippou, Steven D. Shnyder, Laurence H. Patterson, Helen M. Sheldrake
Summary: This study presents a new ligand-mimetic beta 3 integrin antagonist that exhibits high activity against alpha v beta 3 and moderate affinity for alpha IIb beta 3, suggesting a new approach to integrin targeting in cancer.
Article
Hematology
Sevasti B. Koukouritaki, Aye Myat M. Thinn, Katrina J. Ashworth, Juan Fang, Haley S. Slater, Lily M. Du, Huong Thi Thu Nguyen, Xavier Pillois, Alan T. Nurden, Christopher J. Ng, Jorge Di Paola, Jieqing Zhu, David A. Wilcox
Summary: This report identifies a novel variant form of Glanzmann thrombasthenia, exhibiting only mild bleeding. Platelets cannot aggregate ex vivo with physiological agonists, but display moderate ex vivo platelet adhesion and aggregation. Reduced expression of & alpha;IIb & beta;3 on quiescent platelets and activation-dependent antibodies suggest an intrinsic activation phenotype. Genetic analysis reveals a single F153S & beta;3 substitution, suggesting its important role in integrin structure/function. Disruption of F153 & beta;3 significantly alters normal integrin/platelet function, but reduced expression of & alpha;IIbS153 & beta;3 may be compensated by hyperactive conformation promoting viable hemostasis.
Article
Hematology
Kristin Jahn, Stefan Handtke, Raghavendra Palankar, Thomas P. Kohler, Jan Wesche, Martina Wolff, Janina Bayer, Christiane Wolz, Andreas Greinacher, Sven Hammerschmidt
Summary: This study investigated the effects of Staphylococcus aureus and Streptococcus pneumoniae toxins on human platelets. The results showed that alpha-hemolysin of S. aureus had a significant impact on platelet activation and thrombus formation, while other toxins had little effect. These findings may have clinical relevance for the treatment of S. aureus-induced endocarditis.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Plant Sciences
Jung-Hae Shin, Hyuk-Woo Kwon, Muhammad Irfan, Man Hee Rhee, Dong-Ha Lee
Summary: The study showed that G-Rk1 has an inhibitory effect on human platelet aggregation, particularly more effective on collagen-stimulated platelet aggregation. It can also suppress the activity of various platelet signaling molecules, thus blocking platelet formation of thrombosis.
JOURNAL OF GINSENG RESEARCH
(2021)
Article
Cell Biology
M. Y. Koker, N. Sarper, C. Albayrak, B. Zulfikar, E. Zengin, B. Saraymen, D. Albayrak, B. Koc, H. Avcilar, M. Karakukcu, C. Chenet, F. Bianchi, A. G. de Brevern, R. Petermann, V Jallu
Summary: This study reported platelet phenotypes and allelic variations in 28 Turkish GT patients, and investigated the effects of different variants on alpha IIb beta 3 expression using transfected cell lines. New alleles were described, and it was suggested that some variations might be new causes of GT.
Article
Hematology
Jianmin Liu, Fan Lu, Sujay Subbayya Ithychanda, Marcin Apostol, Mitali Das, Gauravi Deshpande, Edward F. Plow, Jun Qin
Summary: This study reveals that filamin associates with both inactive and active forms of alpha IIb ss 3, promoting platelet spreading. Furthermore, the study demonstrates that filamin undergoes spatiotemporal rearrangement upon alpha IIb ss 3 activation, binding to the alpha IIb cytoplasmic tail alone. This novel alpha IIb CT-filamin-actin linkage plays a crucial role in integrin outside-in signaling.
Article
Multidisciplinary Sciences
Joanne L. Dunster, Jo L. Mitchell, Yasmin M. M. Mohammed, Kirk A. Taylor, Jonathan M. Gibbins, Chris Jones
Summary: This paper describes a flow cytometry-based platelet function assay that enables simultaneous data acquisition and sample stimulation and utilizes newly developed bespoke open-source software (Kinetx) to enable quantitative kinetic measurements of platelet granule release, fibrinogen binding, and intracellular calcium flux. This allows realtime platelet activation metrics, such as rate, acceleration, time to peak-rate, time to peak-calcium, and qualitative shape changes, to be accurately and reproducibly measured and categorized, giving a unique insight into platelets' behavior during the first stages of activation.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Multidisciplinary Sciences
Brian D. D. Adair, Jian-Ping Xiong, Mark Yeager, M. Amin Arnaout
Summary: This study determines the cryoEM structure of full-length platelet integrin αIIbβ3 in both its apo and eptifibatide-bound states, providing insights into its conformational changes in response to intracellular signals and drug binding, and suggesting potential adverse effects on platelet hemostasis.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Joy R. Wright, Sarah Jones, Sasikumar Parvathy, Leonard K. Kaczmarek, Ian Forsythe, Richard W. Farndale, Jonathan M. Gibbins, Martyn P. Mahaut-Smith
Summary: Kv1.3 deficiency in platelets leads to enhanced ADP-induced platelet aggregation and secretion, as well as increased surface expression of platelet integrin alpha(IIb); however, in vivo thrombus formation experiments show no significant difference compared to wild type mice, suggesting compensatory pro-thrombotic pathways may be at play. Kv1.3 plays a role in modulating integrin-dependent platelet adhesion, with implications for understanding its contribution to normal physiological platelet function and disease models.
Article
Obstetrics & Gynecology
Bethany Ellen Jakubowski, Richard Stevens, Hannah Wilson, Layla Lavallee, Lesley Brittain, Carole Crawford, James Hodgkinson, Lisa Hinton, Lucy Mackillop, Lucy C. Chappell, Richard J. McManus, Katherine Louise Tucker
Summary: The study aimed to determine the accuracy of self-testing for proteinuria during pregnancy. The results showed that pregnant women can visually read a dipstick for urinary protein with similar accuracy to antenatal healthcare professionals. Self-testing has the potential to be part of self-monitoring during pregnancy.
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
(2022)
Article
Medicine, General & Internal
Katherine L. Tucker, Sam Mort, Ly-Mee Yu, Helen Campbell, Oliver Rivero-Arias, Hannah M. Wilson, Julie Allen, Rebecca Band, Alison Chisholm, Carole Crawford, Greig Dougall, Lazarina Engonidou, Marloes Franssen, Marcus Green, Sheila Greenfield, Lisa Hinton, James Hodgkinson, Layla Lavallee, Paul Leeson, Christine McCourt, Lucy Mackillop, Jane Sandall, Mauro Santos, Lionel Tarassenko, Carmelo Velardo, Lucy Yardley, Lucy C. Chappell, Richard J. McManus
Summary: The use of blood pressure self-monitoring with telemonitoring did not lead to significantly earlier detection of hypertension in pregnant individuals at higher risk of preeclampsia, compared to usual care.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2022)
Article
Medicine, General & Internal
Lucy C. Chappell, Katherine L. Tucker, Ushma Galal, Ly-Mee Yu, Helen Campbell, Oliver Rivero-Arias, Julie Allen, Rebecca Band, Alison Chisholm, Carole Crawford, Greig Dougall, Lazarina Engonidou, Marloes Franssen, Marcus Green, Sheila Greenfield, Lisa Hinton, James Hodgkinson, Layla Lavallee, Paul Leeson, Christine McCourt, Lucy Mackillop, Jane Sandall, Mauro Santos, Lionel Tarassenko, Carmelo Velardo, Hannah Wilson, Lucy Yardley, Richard J. McManus
Summary: Among individuals with pregnancy hypertension, blood pressure self-monitoring did not lead to significantly improved clinic-based blood pressure control.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2022)
Article
Medicine, General & Internal
Jamie Kitt, Annabelle Frost, Jill Mollison, Katherine Louise Tucker, Katie Suriano, Yvonne Kenworthy, Annabelle McCourt, William Woodward, Cheryl Tan, Winok Lapidaire, Rebecca Mills, Maryam Khan, Elizabeth M. Tunnicliffe, Betty Raman, Mauro Santos, Cristian Roman, Henner Hanssen, Lucy Mackillop, Alexandra Cairns, Basky Thilaganathan, Lucy Chappell, Christina Aye, Adam J. Lewandowski, Richard J. McManus, Paul Leeson
Summary: This trial aims to evaluate whether optimized blood pressure control during the puerperium can reduce blood pressure levels at 6 months postpartum and improve cardiovascular and cerebrovascular phenotypes. The trial will recruit 200 women aged 18 years or older diagnosed with pre-eclampsia or gestational hypertension and requiring antihypertensive medication. The participants will be randomly assigned to receive either physician-optimized self-management or usual care. Various blood pressure parameters, cardiovascular assessments, multiorgan MRI, blood samples, and physical activity monitoring will be used to assess the outcomes. An additional group of 20 women with a normotensive pregnancy will be recruited as a comparator group for endothelial cellular biomarkers.
Review
Medicine, General & Internal
Bethany Ellen Jakubowski, Lisa Hinton, Jaspreet Khaira, Nia Roberts, Richard J. McManus, Katherine Louise Tucker
Summary: This study found that pregnant women with chronic conditions in pregnancy often self-manage primarily for the health of their baby, while facing barriers such as anxiety, lack of understanding, and inadequate support from families and healthcare professionals. Further research is needed on a range of self-management of chronic conditions in pregnancy.
Article
Multidisciplinary Sciences
Edurne Mugarza, Febe van Maldegem, Jesse Boumelha, Christopher Moore, Sareena Rana, Miriam Llorian Sopena, Philip East, Rachel Ambler, Panayiotis Anastasiou, Pablo Romero-Clavijo, Karishma Valand, Megan Cole, Miriam Molina-Arcas, Julian Downward
Summary: Recently developed KRAS(G12C) inhibitory drugs benefit lung cancer patients with KRAS(G12C) mutations, but drug resistance is common. These drugs indirectly affect antitumor immunity by reversing immunosuppression caused by oncogenic KRAS. However, the combination of KRAS(G12C) inhibitors with immune checkpoint blockade only provides synergistic benefit in highly immunogenic tumor models.
Article
Biochemistry & Molecular Biology
Ilaria De Simone, Constance C. F. M. J. Baaten, Martine Jandrot-Perrus, Jonathan M. Gibbins, Hugo ten Cate, Johan W. M. Heemskerk, Chris Jones, Paola E. J. van der Meijden
Summary: Platelet and coagulation activation are reciprocal processes, and factors other than thrombin or fibrin can induce platelet activation via GPVI and PAR receptors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
May Zaw Thin, Christopher Moore, Thomas Snoeks, Tammy Kalber, Julian Downward, Axel Behrens
Summary: In this paper, a method of lung nodule image acquisition and analysis using a micro-computed tomography scanner is introduced for translational research in lung cancer that closely mimics clinical environments. The method has the advantages of low radiation dose, high resolution, and high-throughput imaging, and utilizes specific image analysis tools for identifying different types of lung tumors.
Article
Multidisciplinary Sciences
Claudio Bussi, Tiaan Heunis, Enrica Pellegrino, Elliott M. Bernard, Nourdine Bah, Mariana Silva Dos Santos, Pierre Santucci, Beren Aylan, Angela Rodgers, Antony Fearns, Julia Mitschke, Christopher Moore, James MacRae, Maria Greco, Thomas Reinheckel, Matthias Trost, Maximiliano G. Gutierrez
Summary: This study reveals that limited lysosomal damage leads to changes in the mitochondrial proteome and the modulation of macrophage immunometabolism. It shows that protease leakage from lysosomes triggers a cell death-independent proteolytic remodeling of the mitochondrial proteome in macrophages.
NATURE COMMUNICATIONS
(2022)
Article
Obstetrics & Gynecology
L. Pealing, K. L. Tucker, B. Fletcher, E. Lawley, L. C. Chappell, R. J. McManus, S. Ziebland
Summary: This study explores the feasibility and acceptability of self-monitoring of blood pressure (SMBP) for pregnant women with chronic hypertension. The results show that both women and clinicians find SMBP acceptable and beneficial in improving blood pressure control and knowledge. More research is needed to interpret and integrate home blood pressure readings for better management.
PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH
(2022)
Article
Obstetrics & Gynecology
Hannah Wilson, Katherine L. Tucker, Alison Chisholm, James Hodgkinson, Layla Lavallee, Lucy Mackillop, Alexandra E. Cairns, Lisa Hinton, Charlie Podschies, Lucy C. Chappell, Richard J. McManus
Summary: This study evaluated the implementation of self-monitoring of blood pressure (SMBP) in English maternity units during the COVID-19 pandemic. The results showed that SMBP was mainly used for hypertensive or high-risk pregnant women, reducing the need for face-to-face contacts and empowering women to have more control and insight into their own blood pressure. However, there were challenges in setting up SMBP services rapidly and integrating them into existing care pathways.
PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH
(2022)
Article
Obstetrics & Gynecology
Lucy Goddard, Nerys M. Astbury, Richard J. McManus, Katherine Tucker, Jennifer MacLellan
Summary: This study conducted a qualitative evidence synthesis of local NHS clinical practice guidelines in England. The findings showed that local weight management guidelines for pregnant women are rooted in a medical model rather than the partnership approach advocated in national maternity policy. This synthesis highlights the challenges faced by healthcare professionals and the experiences of pregnant women receiving weight management care. Future research should focus on tools utilized by maternity care providers to achieve a partnership approach and empower pregnant and postnatal individuals in their journey through motherhood.
BMC PREGNANCY AND CHILDBIRTH
(2023)
Review
Obstetrics & Gynecology
Lucy Goddard, Rajan Patel, Nerys M. Astbury, Katherine Tucker, Richard J. McManus
Summary: This study aimed to evaluate the effects of lifestyle interventions in pregnant people with chronic hypertension and/or pre-existing diabetes using randomized controlled trials (RCTs). Nine RCTs including 7438 pregnant women were eligible. The results showed a lack of primary interventional trials in pregnant populations with chronic hypertension and/or pre-existing diabetes, indicating the need for further research in this area.
PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH
(2023)
Article
Polymer Science
Jacob Ranjbar, Wanjiku Njoroge, Jonathan M. Gibbins, Paul Roach, Ying Yang, Alan G. S. Harper
Summary: Researchers have developed a 3D hydrogel model that mimics the medial and adventitial layers of the human artery, allowing for the formation of blood clots under physiological flow conditions. This model has the potential to replace animal experimentation and provide a more realistic in vitro model for studying thrombosis.