Article
Biochemistry & Molecular Biology
Marcela Montilla, Isabel Atienza-Navarro, Francisco Jose Garcia-Cozar, Carmen Castro, Francisco Javier Rodriguez-Martorell, Felix A. Ruiz
Summary: Polyphosphate (polyP) plays an important modulatory role in the binding of von Willebrand factor (VWF) and Factor VIII (FVIII) in blood coagulation, and may be used in developing new therapies to activate VWF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Ferdows Atiq, Jens van de Wouw, Oana Sorop, Ilkka Heinonen, Moniek P. M. de Maatl, Daphne Merkus, Dirk J. Duncker, Frank W. G. Leebeek
Summary: The levels of von Willebrand factor (VWF) and factor VIII (FVIII) are associated with an increased risk of cardiovascular disease. Short-term hyperglycemia and dyslipidemia increase FVIII levels independently of VWF, while long-term diabetes and hypercholesterolemia increase VWF levels through endothelial dysfunction and atherosclerosis, indicating VWF as a biomarker for advanced cardiovascular disease.
THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Wenjing Cao, Aria R. Trask, Antonia I. Bignotti, Lindsey A. George, Bhavya S. Doshi, Denise E. Sabatino, Noritaka Yada, Liang Zheng, Rodney M. Camire, X. Long Zheng
Summary: This study aims to determine the effect of FVIII on VWF proteolysis and homeostasis. Through mouse models, recombinant FVIII infusion, and patients with hemophilia A, the study concludes that FVIII plays a pivotal role in regulating VWF proteolysis and homeostasis under various conditions.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Eugenia Biguzzi, Simona Maria Siboni, Saskia le Cessie, Luciano Baronciani, Frits R. Rosendaal, Astrid van Hylckama Vlieg, Flora Peyvandi
Summary: The study evaluated the differential increase of VWF and FVIII:C with age among different ages and types of VWD.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Editorial Material
Hematology
Emma-Ruoqi Xu, Jonas Emsley
Summary: In this issue of Blood, Fuller et al reveal the first detailed structure of the key hemostatic complex formed between factor VIII (FVIII) and von Willebrand factor (VWF).
Review
Hematology
Xue D. Manz, Harm Jan Bogaard, Jurjan Aman
Summary: Increasing evidence suggests that inflammation promotes thrombosis via VWF-mediated mechanisms, and aberrant regulation of VWF is linked to various cardiovascular diseases. Recent insights from clinical diseases provide evidence for direct molecular links between inflammation and thrombosis.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Hematology
Hiroaki Yaoi, Yasuaki Shida, Takehisa Kitazawa, Midori Shima, Keiji Nogami
Summary: Patients with Type 2N von Willebrand disease showed defective thrombus formation correlated with bleeding phenotype, which was improved by Emicizumab, enhancing thrombin generation and fibrin formation. The interactions between FVIII and VWF play an important role in platelet-fibrin interactions during thrombus formation and may be targeted as an alternative therapy for these patients.
THROMBOSIS RESEARCH
(2021)
Letter
Cardiac & Cardiovascular Systems
Marios K. Georgakis, Rainer Malik, Xue Li, Dipender Gill, Michael G. Levin, Ha My T. Vy, Renae Judy, Marylyn Ritchie, Shefali S. Verma, Girish N. Nadkarni, Scott M. Damrauer, Evropi Theodoratou, Martin Dichgans
Summary: Additional digital content is available for reference in the text.
Review
Physiology
Roddy Walsh, Sean J. Jurgens, Jeanette Erdmann, Connie R. Bezzina
Summary: Genome-wide association studies (GWAS) have identified common genetic variants associated with traits and diseases, providing insights into genetic architecture, correlations across traits and diseases, and potential clinical applications. The utilization of GWAS in cardiovascular diseases and associated phenotypic traits has been facilitated by multicenter registry studies and large biobank data sets. However, challenges still exist in this field and need to be addressed.
PHYSIOLOGICAL REVIEWS
(2023)
Review
Biochemistry & Molecular Biology
Juan A. De Pablo-Moreno, Luis Javier Serrano, Luis Revuelta, Maria Jose Sanchez, Antonio Liras
Summary: The vascular endothelium plays a crucial role in hemostasis, maintaining a delicate balance between procoagulant and anticoagulant proteins, as well as fibrinolytic and antifibrinolytic factors. Coagulation disorders can be caused by mutations in coagulation factors or disruptions in the regulatory mechanisms. Treatment options include replacement and nonreplacement therapies, as well as administration of antifibrinolytic agents. Targeted therapies, such as monoclonal antibodies and interfering RNA therapies, are also being developed. The treatment approach for thrombophilia, disseminated intravascular coagulation, and severe thrombophilia varies depending on the specific condition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Haarin Chun, John R. Pettersson, Svetlana A. Shestopal, Wells W. Wu, Ekaterina S. Marakasova, Philip Olivares, Stepan S. Surov, Mikhail V. Ovanesov, Rong-Fong Shen, Andrey G. Sarafanov
Summary: A study aimed to isolate and characterize a fraction of coagulation factor VIII (FVIII) product that is unable to bind von Willebrand factor (VWF). The fraction, named FVIIIFT, was found in various contents in all tested products, showing lower functional activity compared to the able fraction FVIIIEL. The study demonstrated potential methods to control this impurity in FVIII products for improved efficacy in hemophilia A therapy.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Beverly A. Schaefer, Dunlei Cheng, Peter Kouides
Summary: Obesity prevalence was similar among participants with LVWF and T1VWD in the ATHNdataset, but higher BMI levels were associated with elevated FVIII. Further research is needed to evaluate the impact of obesity on bleeding phenotype and treatment practices.
Article
Multidisciplinary Sciences
Triin Laisk, Maarja Lepamets, Mariann Koel, Erik Abner, Andres Metspalu, Reedik Maegi
Summary: Pernicious anemia is a rare condition with a clear autoimmune basis, often caused by autoimmune gastritis, and associated with a higher risk of other autoimmune disorders. A genome-wide association study meta-analysis identified significant associations between pernicious anemia and genetic risk factors in genes such as PTPN22, PNPT1, HLA-DQB1, IL2RA, and AIRE.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Mary Hoekstra, Hao Yu Chen, Jian Rong, Line Dufresne, Jie Yao, Xiuqing Guo, Michael Y. Tsai, Sotirios Tsimikas, Wendy S. Post, Ramachandran S. Vasan, Jerome I. Rotter, Martin G. Larson, George Thanassoulis, James C. Engert
Summary: This study identified a novel locus APOH influencing Lp(a) levels in individuals of European ancestry and confirmed previous associations at LPA, APOE, and CETP. Further research is needed to determine the precise role of beta 2GPI in influencing Lp(a) levels and its potential as a therapeutic target.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Hematology
Paolo Simioni, Stefano Cagnin, Francesca Sartorello, Gabriele Sales, Luca Pagani, Cristiana Bulato, Sabrina Gavasso, Francesca Nuzzo, Francesco Chemello, Claudia M. Radu, Daniela Tormene, Luca Spiezia, Tilman M. Hackeng, Elena Campello, Elisabetta Castoldi
Summary: This study identified the molecular basis of high FVIII levels leading to severe thrombophilia in two Italian families, involving a tandem duplication of the proximal portion of the F8 gene. This rearrangement led to upregulation of F8 messenger RNA and transcriptional enhancement, potentially mediating the severe thrombophilia observed in carriers of the duplication.
Article
Endocrinology & Metabolism
Jeroen H. P. M. van der Velde, Sebastiaan C. Boone, Esther Winters-van Eekelen, Matthijs K. C. Hesselink, Vera B. Schrauwen-Hinderling, Patrick Schrauwen, Hildo J. Lamb, Frits R. Rosendaal, Renee de Mutsert
Summary: This study found that the number of breaks in sedentary time was not associated with lower liver fat content or reduced insulin resistance. However, engaging in moderate-to-vigorous physical activity in the afternoon or evening was associated with a reduction of up to 25% in insulin resistance. Further research should investigate whether the timing of physical activity also plays an important role in the occurrence of type 2 diabetes.
Article
Critical Care Medicine
Ishita P. Miah, Anastassia Blanter, Yeliz Tank, Erik W. van Zwet, Frits R. Rosendaal, Wilco C. Peul, Ruben Dammers, Dana C. Holl, Hester F. Lingsma, Heleen M. den Hertog, Joukje van der Naalt, Korne Jellema, Niels A. Van der Gaag
Summary: Surgical intervention is the main treatment strategy for chronic subdural hematoma. Recent trials have shown that dexamethasone therapy is ineffective in symptomatic patients. This study aimed to identify which hematoma subtype is favorable for dexamethasone therapy.
JOURNAL OF NEUROTRAUMA
(2023)
Article
Biochemistry & Molecular Biology
Jean-Baptiste Pingault, Wikus Barkhuizen, Biyao Wang, Laurie J. Hannigan, Espen Moen Eilertsen, Elizabeth Corfield, Ole A. Andreassen, Helga Ask, Martin Tesli, Ragna Bugge Askeland, George Davey Smith, Camilla Stoltenberg, Neil M. Davies, Ted Reichborn-Kjennerud, Eivind Ystrom, Alexandra Havdahl
Summary: This study explores the mechanisms underlying the intergenerational transmission of risk for ADHD traits. The results suggest that genetic factors play a major role in this transmission, rather than environmental influences from parents. The findings emphasize the importance of considering genetic transmission in understanding the development of ADHD.
MOLECULAR PSYCHIATRY
(2023)
Meeting Abstract
Clinical Neurology
Yousef Hannawi, Dhananjay Vaidya, Lisa R. Yanek, Brian G. Kral, Lewis C. Becker, Paul A. Nyquist
Article
Clinical Neurology
Mark K. Bakker, Jos P. Kanning, Gad Abraham, Amy E. Martinsen, Bendik S. Winsvold, John-Anker Zwart, Romain Bourcier, Tomonobu Sawada, Masaru Koido, Yoichiro Kamatani, Sandrine Morel, Philippe Amouyel, Stephanie Debette, Philippe Bijlenga, Takiy Berrandou, Santhi K. Ganesh, Nabila Bouatia-Naji, Gregory Jones, Matthew Bown, Gabriel J. E. HUNT All In Stroke, Jan H. CADISP Grp, Ynte M. Int Consortium Blood Pressure, Int Headache Genetics Consortium, ISGC, Intracranial Aneurysm Working Grp, Gabriel J. E. Rinkel, Jan Veldink, Ynte Ruigrok
Summary: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to have potential for genetic risk prediction. However, a genetic risk score incorporating these factors only showed limited predictive value for IA presence and ASAH incidence, suggesting that it may not be suitable for daily clinical use.
Article
Health Care Sciences & Services
Ellen Rabben Svedahl, Kristine Pape, Bjarne Austad, Gunnhild Aberge Vie, Kjartan Sarheim Anthun, Fredrik Carlsen, Neil M. Davies, Johan Hakon Bjorngaard
Summary: This study aims to assess the impact of altering referral thresholds from out-of-hours services on further use of health services and risk of death among older patients. Using patient data from primary and specialised health services, as well as demographic data, and employing multivariable adjusted and instrumental variable analysis, the study finds that these referrals have a significant impact on healthcare utilization among older patients, while also reducing the risk of death. Therefore, raising the referral threshold should be done cautiously, ensuring the accuracy of referral decisions through high-quality randomized controlled trials.
BMJ QUALITY & SAFETY
(2023)
Article
Cardiac & Cardiovascular Systems
Hao Yu Chen, Christian Dina, Aeron M. Small, Christian M. Shaffer, Rebecca T. Levinson, Anna Helgadottir, Romain Capoulade, Hans Markus Munter, Andreas Martinsson, Benjamin J. Cairns, Linea C. Trudso, Mary Hoekstra, Hannah A. Burr, Thomas W. Marsh, Scott M. Damrauer, Line Dufresne, Solena Le Scouarnec, David Messika-Zeitoun, Dilrini K. Ranatunga, Rachel A. Whitmer, Amelie Bonnefond, Garoar Sveinbjornsson, Ragnar Danielsen, David O. Arnar, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, Daniel F. Gudbjartsson, Hilma Holm, Jonas Ghouse, Morten Salling Olesen, Alex H. Christensen, Susan Mikkelsen, Rikke Louise Jacobsen, Joseph Dowsett, Ole Birger Vesterage Pedersen, Christian Erikstrup, Sisse R. Ostrowski, Christopher J. O'Donnell, Matthew J. Budoff, Vilmundur Gudnason, Wendy S. Post, Jerome Rotter, Mark Lathrop, Henning Bundgaard, Bengt Johansson, Johan Ljungberg, Ulf Naslund, Thierry Le Tourneau, J. Gustav Smith, Quinn S. Wells, Stefan Soderberg, Kari Stefansson, Jean-Jacques Schott, Daniel J. Rader, Robert Clarke, James C. Engert, George Thanassoulis
Summary: This study conducted a genome-wide meta-analysis and discovered 17 loci associated with calcific aortic stenosis. The integration of functional, expression, and cross-phenotype data revealed the mechanisms of this disease. Dyslipidemia, inflammation, calcification, and adiposity were identified as important factors in the etiology of calcific aortic stenosis.
EUROPEAN HEART JOURNAL
(2023)
Article
Cardiac & Cardiovascular Systems
Gregory G. Schwartz, Michael Szarek, Deepak L. Bhatt, Vera A. Bittner, Maja Bujas-Bobanovic, Rafael Diaz, Sergio Fazio, Zlatko Fras, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Garen Manvelian, Robert Pordy, Kausik K. Ray, Michel Scemama, Harvey D. White, Ph Gabriel Steg
Summary: Long-term placebo-controlled trials have shown clinical benefits that persist after the end of the trial. This study aims to investigate whether similar effects can be seen with short-term very low low-density lipoprotein cholesterol (LDL-C) levels achieved using statin and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy.
EUROPEAN HEART JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Jose A. Inia, Geurt Stokman, Elsbet J. Pieterman, Martine C. Morrison, Aswin L. Menke, Lars Verschuren, Martien P. M. Caspers, Martin Giera, J. Wouter Jukema, Anita M. van den Hoek, Hans M. G. Princen
Summary: Patients with metabolic syndrome are often prescribed statins to prevent cardiovascular disease, but their effects on NASH are lacking. This study found that atorvastatin can significantly reduce hepatic steatosis, inflammation, and fibrosis, as well as prevent cholesterol crystal formation and NLRP3 inflammasome activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Ariadne Bosman, W. Nadia H. Koek, Natalia Campos-Obando, Bram C. J. van der Eerden, M. A. Ikram, Andre G. Uitterlinden, Johannes P. T. M. van Leeuwen, M. C. Zillikens
Summary: Sex differences in serum phosphate and calcium were observed, with women having higher levels than men. Adjustments for hormonal factors, such as estradiol and testosterone, partially explained these sex differences. The findings suggest that estradiol may play a role in sex differences in serum calcium, while testosterone may contribute to sex differences in serum phosphate.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Amir S. Heravi, Di Zhao, Erin D. Michos, Henrique Doria De Vasconcellos, Bharath Ambale-Venkatesh, Donald Lloyd-Jones, Pamela J. Schreiner, Jared P. Reis, James M. Shikany, Cora E. Lewis, Chiadi E. Ndumele, Eliseo Guallar, Pamela Ouyang, Ron C. Hoogeveen, Joao A. C. Lima, Wendy S. Post, Dhananjay Vaidya
Summary: This study investigated the association between oxidative stress and cardiovascular diseases, finding that female individuals had higher levels of oxidative stress. Furthermore, factors such as higher body mass index, lipid levels, smoking, and lack of physical activity were also associated with higher oxidative stress. This suggests that oxidative stress may play an important role in cardiovascular diseases.
Article
Endocrinology & Metabolism
Claes Ohlsson, Maria Nethander, Anna-Karin Norlen, Matti Poutanen, Elias Freyr Gudmundsson, Thor Aspelund, Sigurdur Sigurdsson, Henrik Ryberg, Vilmundur Gudnason, Asa Tivesten
Summary: This study found an inverse association between serum levels of DHEA and testosterone and coronary artery calcification in elderly men, partially independently from each other. These results raise the question whether androgens produced by both the adrenals and the testes may contribute to male cardiovascular health.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Genetics & Heredity
Yi Li, Ziyi Xiong, Manfei Zhang, Pirro G. Hysi, Yu Qian, Kaustubh Adhikari, Jun Weng, Sijie Wu, Siyuan Du, Rolando Gonzalez-Jose, Lavinia Schuler-Faccini, Maria-Catira Bortolini, Victor Acuna-Alonzo, Samuel Canizales-Quinteros, Carla Gallo, Giovanni Poletti, Gabriel Bedoya, Francisco Rothhammer, Jiucun Wang, Jingze Tan, Ziyu Yuan, Li Jin, Andre G. Uitterlinden, Mohsen Ghanbari, M. Arfan Ikram, Tamar Nijsten, Xiangyu D. Zhu, Zhen Lei, Peilin Jia, Andres Ruiz-Linares, Timothy D. Spector, Sijia Wang, Manfred Kayser, Fan Liu
Summary: In this study, the genetic basis of human ear morphology was investigated using deep learning analysis of digital face images in individuals from three continents. The study identified 16 genetic loci associated with ear morphology, eight of which were newly discovered. Furthermore, gene editing experiments in mice confirmed the impact of two ear-associated genes on ear morphology. This study provides new insights into the complex genetics of the human ear.
Article
Biotechnology & Applied Microbiology
Sairam Behera, Jonathon LeFaive, Peter Orchard, Medhat Mahmoud, Luis F. Paulin, Jesse Farek, Daniela C. Soto, Stephen C. J. Parker, Albert V. Smith, Megan Y. Dennis, Justin M. Zook, Fritz J. Sedlazeck
Summary: The current version of the human reference genome, GRCh38, contains errors including falsely duplicated and collapsed regions. These errors have an impact on the variant calling of protein-coding genes, some of which are medically relevant. In this study, a new remapping approach called FixItFelix is presented, along with a modified version of the GRCh38 reference genome. This approach improves the analysis of these genes within minutes without changing the coordinates, as demonstrated using multi-ethnic control samples for population variant calling and eQTL studies.
Article
Genetics & Heredity
Kristin L. Young, Virginia Fisher, Xuan Deng, Jennifer A. Brody, Misa Graff, Elise Lim, Bridget M. Lin, Hanfei Xu, Najaf Amin, Ping An, Stella Aslibekyan, Alison E. Fohner, Bertha Hidalgo, Petra Lenzini, Robert Kraaij, Carolina Medina-Gomez, Ivana Prokic, Fernando Rivadeneira, Colleen Sitlani, Ran Tao, Jeroen van Rooij, Di Zhang, Jai G. Broome, Erin J. Buth, Benjamin D. Heavner, Deepti Jain, Albert Smith, Kathleen Barnes, Meher Preethi Boorgula, Sameer Chavan, Dawood Darbar, Mariza De Andrade, Xiuqing Guo, Jeffrey Haessler, Marguerite R. Irvin, Rita R. Kalyani, Sharon L. R. Kardia, Charles Kooperberg, Wonji Kim, Rasika A. Mathias, Merry-Lynn McDonald, Braxton D. Mitchell, Patricia A. Peyser, Elizabeth A. Regan, Susan Redline, Alexander P. Reiner, Stephen S. Rich, Jerome I. Rotter, Jennifer A. Smith, Scott Weiss, Kerri L. Wiggins, Lisa R. Yanek, Donna Arnett, Nancy L. Heard-Costa, Suzanne Leal, Danyu Lin, Barbara McKnight, Michael Province, Cornelia M. van Duijn, Kari E. North, L. Adrienne Cupples, Ching-Ti Liu
Summary: Anthropometric traits, such as body size and shape, are heritable risk factors for cardiometabolic disorders. Whole-exome sequence analysis was performed on height, BMI, and WHR, and associations were identified with specific genetic variants. Replication of these findings was done in independent cohorts, and potential functional genes within known height loci were identified. The study highlights the importance of genomic sequencing in genetic association studies, while also showing the challenges in identifying rare genetic variants.
HUMAN GENETICS AND GENOMICS ADVANCES
(2023)