tbuckley/cabot-search huggingface dataset:
Prenatal Metal Mixtures and Birth Weight for Gestational Age in a Predominately Lower-Income Hispanic Pregnancy Cohort in Los Angeles
Authors: Caitlin G. Howe, Birgit Claus Henn, Sandrah P. Eckel, Shohreh F. Farzan, Brendan H. Grubbs, Thomas A. Chavez, Tahlia L. Hodes, Dema Faham, Laila Al-Marayati, Deborah Lerner, Alyssa Quimby, Sara Twogood, Michael J. Richards, John D. Meeker, Theresa M. Bastain, Carrie V. Breton
Journal: Environmental Health Perspectives (2020)

Background: Reduced fetal growth increases the risk for adverse health outcomes. Growing evidence suggests that metal exposures contribute to reduced fetal growth, but little is known about the effects of complex metal mixtures. Objectives: We investigated the impact of a complex mixture of metals on birth weight for gestational age (BW for GA) in the Maternal and Developmental Risks from Environmental and Social Stressors study, a predominately lower-income Hispanic pregnancy cohort in Los Angeles, California. Methods: Cadmium (Cd), cobalt (Co), mercury (Hg), nickel (Ni), molybdenum (Mo), lead (Pb), antimony (Sb), tin (Sn), and thallium (Tl) were measured by inductively coupled plasma mass spectrometry (ICP-MS) in maternal urine samples collected in early pregnancy (median GA: 13.1 wk). Speciated urinary arsenic (As) (inorganic+monomethyl+dimethyl As) was measured by high-performance liquid chromatography coupled to ICP-MS. Primary analyses focused on a mixture of seven metals that have previously been associated individually with fetal growth (i.e., As, Cd, Co, Hg, Ni, Pb, Tl) (n=262). In exploratory analyses, we additionally examined three metals that have been less studied in relation to fetal growth (i.e., Mo, Sb, Sn). Covariate-adjusted Bayesian kernel machine regression was used to investigate metal mixture associations with BW for GA z-scores. Results: In primary analyses, Hg and Ni ranked highest as predictors of BW for GA. An inverse linear association was estimated for Hg, whereas a positive association was estimated for Ni at low-to-moderate concentrations. A potential interaction between Hg and Ni was also identified. In our exploratory analysis, Sb ranked highest as a predictor of BW for GA, followed by Hg and Ni. Conclusions: Our findings suggest that in this understudied population, Hg may reduce fetal growth, whereas Ni may promote fetal growth. We also identified Sb as a potential metal of concern for this population, which merits additional investigation. https://doi.org/10.1289/EHP7201
Rare Case Report of Adult T-Cell Leukemia / Lymphoma (ATLL), in the City of Macau- Rio Grande Do Norte; Brazil
Authors: Hugo Henrique de Freitas Ferreira, Alessandra Suelen Jardim Silva, Lenilton Silva DA Silva Júnior, Gustavo Henrique de Medeiros Oliveira, Maria das Graças Pereira Araujo, Victor lima Soares, Frank Bahia, Taissa Moura Oliveira, Dany GKC Silva, Valéria SF Sales, Aldair Sousa Paiva, Geraldo Barroso Cavalcanti
Journal: Blood (2020)
Abstract 282: Role of a Disintegrin and Metalloproteinase 15 in Cardiac Hypertrophy and Fibrosis Following Pressure Overload
Authors: Priya Aujla, Sayantan Jana, Michael Chute, Zamaneh Kassiri
Journal: Circulation Research (2020)

Introduction: Disintegrin and metalloproteinases (ADAMs) are membrane-bound cell surface enzymes that are capable of both proteolytic functions (via the metalloproteinase domain) and adhesive functions (via the disintegrin domain), whereby they can influence cell function and extracellular matrix (ECM) remodelling in the heart. ADAM15 is unique among the ADAMs, as it is also capable of degrading ECM proteins. ADAM12 and ADAM17 have been reported to regulate cardiac hypertrophy, but the role of ADAM15 in cardiac hypertrophy is not known. This study investigates the role of ADAM15 in cardiac hypertrophy and fibrosis following pressure overload. Methods &amp; Results: Genetically modified male ADAM15-deficient ( Adam15 -/- ) and wildtype (WT) mice were subjected to cardiac pressure overload by transverse aortic constriction (TAC). Cardiac function and structural remodelling were assessed using echocardiography at 2-, and 6-wks post-TAC. Hearts were excised at 2-, or 6-wks post-TAC. Adam15 -/- hearts presented greater hypertrophy and decreased cardiac systolic function at 6wks post-TAC, but no difference at 2wks post-TAC compared to WT-TAC mice. Adam15 -/- hearts also showed exacerbated fibrosis at 6wks post-TAC, but not at 2wks post-TAC, compared to WT. Mechanical strain (i.e. pressure overload) triggers two temporally activated pathways leading to an initial compensatory hypertrophy, which can culminate to decompensation and dilated cardiomyopathy. Consistent with the greater hypertrophy, phosphorylation of ERK1/2, JNK1/2/3, and GSK3β was increased in Adam15 -/- mice. The calcineurin-NFAT pathways can mediate pressure overload-induced hypertrophy, but we found that Adam15-deficiency did not impact this pathway. The mechanism responsible for this function of ADAM15 requires further investigation. Conclusion: This study reports a novel cardioprotective function for ADAM15 in pressure overload, where loss of ADAM15 promotes cardiac fibrosis and decompensated cardiac hypertrophy but does not alter the compensated hypertrophic response.
AB0033 Association of c ? reactive protein with bone mineral density and biochemical markers of bone turnover in osteoporosis patients with rheumatoid arthritis
Authors: DA Gukasyan, EL Nasonov, RM Balabanova, AV Smirnov
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To examine the association of C ? reactive protein (CRP) on bone mineral density and biochemical markers of bone turnover in osteoporosis patients with rheumatoid arthritis (RA). <h3>Methods</h3> Out of the 60 female patients with proved diagnosis of RA aged 34–64 years.; Gr. 1: 30 women with preserved menstrual cycle (median age 41,5 years, disease duration 9,5 years, rheumatoid factor positive 80%). Gr. 2: 30 women with postmenopause. (median age 56,2 years, disease duration 10,2 years, rheumatoid factor positive 83,3%). Both groups have not undergone any glucocorticoid or antiosteporodic therapy. Bone mineral density (BMD) was measured with a ?QDR Hologic 1000 plus? by Dual Energy X -Ray Absorptiometry (DEXA) method, for the lumbar spine and in proximal segments of the femur. Concentration of CRP, bone alkaline phosphatase (BAP) and deoxypyridinoline (Dpir) was studded by immunoensymatic method. <h3>Results</h3> In gr.1 of RA patients by with increase of concentration (CRP) &gt; 50 mg/l reliable decrease of BMD was determined in all studied sections of proximal segment of the femur, as compared with patients with CRB £ 50 mg/l level, and in gr. 2 similar change was observed only in BMD L1-L4. Negative correlation between CRB and BMD femoral neck (r = -0,53, ð &lt; 0,005) in RA patients of gr. 2, and in gr.1 with CRB and BMD of femoral neck (r = -0.5, ð &lt; 0,01) was revealed. Direct significant correlation between the level of Dpir and CRP has be revealed in both groups (r = 0,46, ð = 0,04 and r = 0,51, ð = 0,02 relatively). Reliable correlation between BMD L1-L4 and CRP, also between BAP and CRP was not revealed. <h3>Conclusion</h3> Increase of CRB concentration in RA correlated with growing of bone resorption markers and decrease of BMD of femoral neck.
Abstract PO-072: Control of inter- and intra-patient cancer heterogeneity is a predictively accurate explanation for the success of many combination therapies for solid and hematological cancers
Authors: Adam C. Palmer, Ben Izar, Haeun Hwangbo, Peter K. Sorger
Journal: Cancer Research (2020)

Abstract Developing optimal drug combinations is one of the central challenges of cancer treatment research: drug combinations are used to treat most types of cancer, and are almost exclusively responsible for cures of advanced cancers. However, historically successful combination therapies were developed empirically, and the mechanistic basis for their efficacy has been largely speculative. I will present experiments, models, and computational analyses of clinical trial data, to investigate the mechanistic basis of clinically successful combination therapies across 12 types of cancer and 30 different therapies. These studies consistently identify the control of cancer heterogeneity between-patients (inter-tumor) and within-patients (intra-tumor) by independently active drugs as critical contributors to the efficacy of combination therapies in human patients. The key approaches for data analysis and modeling in these studies consist of adapting classical pharmacological concepts to the complex situation of populations of cancers with heterogeneous drug sensitivity. Synergistic drug interactions in humans appears uncommon among approved combination therapies, and even curative regimens exhibit drug additivity in experimental measurements and in clinical outcomes. Mathematical descriptions of heterogeneity in cellular or patient populations, and quantitative experimental measurements of how drug combinations address heterogeneity, lead to accurate predictions of clinical trial results for a diverse range of combination therapies, including those with immune checkpoint inhibitors (correlation between observed and expected Progression Free Survival in 14 trials, Pearson r = 0.98, P &amp;lt; 10^-8) and curative chemotherapy regimens for hematological cancers (correlation between observed and expected response rates and cure rates in 40 years of trials in childhood ALL, Pearson r = 0.99, P &amp;lt; 10^-10). These results have broad significance for the treatment of cancers, for the interpretation of clinical trials, and point to new opportunities to use combination therapies with greater precision. Citation Format: Adam C. Palmer, Ben Izar, Haeun Hwangbo, Peter K. Sorger. Control of inter- and intra-patient cancer heterogeneity is a predictively accurate explanation for the success of many combination therapies for solid and hematological cancers [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-072.
Blinatumomab in Children with Relapsed or Refractory B-Precursor Acute Lymphoblastic Leukemia (R/R-ALL): Final Results of 110 Patients Treated in an Expanded Access Study (RIALTO)
Authors: Franco Locatelli, Gerhard Zugmaier, Noemi Mergen, Peter Bader, Sima Jeha, Paul-Gerhardt Schlegel, Jean-Pierre Bourquin, Rupert Handgretinger, Benoit Brethon, Claudia Rössig, William Kormany, Puneeth Viswagnachar, Christiane Chen-Santel
Journal: Blood (2020)
Long-term remission of cryopyrin-associated periodic syndrome after allogeneic haematopoietic stem cell transplantation
Authors: Takehiko Mori, Masuho Saburi, Maki Hagihara, Masaaki Mori, Rie Yamazaki, Jun Kato
Journal: Annals of the Rheumatic Diseases (2020)

Cryopyrin-associated periodic syndrome (CAPS) is an inherited inflammatory disorder.1 CAPS is characterised by skin rash, fever and the inflammations involving the eyes, ears, bones, joints and meninges. The mutations of NLRP3 encoding interleukin-1 (IL-1) inflammasome protein, cryopyrin, lead to the increased IL-1β secretion. The treatment for CAPS includes symptomatic treatments and IL-1β pathway blocking agents.2–4 Although such agents are effective, they are not curative. Allogeneic haematopoietic stem cell transplantation (HSCT) is widely performed for haematological disorders and some inherited immune disorders. Through allogeneic HSCT, the hosts’ haematopoietic and immune cells are completely replaced by the normal donor cells. Therefore, CAPS could be theoretically cured by allogeneic HSCT; however, there have been no reported patients with CAPS who underwent allogeneic HSCT so far.

A 30-year-old woman had a long-standing history of recurrent symptoms/signs such as fever, skin rash, arthralgia, serious headache and uveitis of the neonatal onset. She had presented a hearing loss since her …
Prognostic Role of C-Reactive Protein, C-Reactive Protein Kinetics and C-Reactive Protein/ Albumin Ratio in Newly Diagnosed B-Cell Chronic Lymphoproliferative Diseases
Authors: Huimin Zhang, Ya Zhang, Xiangxiang Zhou, Xiang Sun, Yang Han, Xinting Hu, Xiaoya Yun, Xin Wang
Journal: Blood (2020)
Pre-pandemic psychiatric disorders and risk of COVID-19: a UK Biobank cohort analysis
Authors: Huazhen Yang, Wenwen Chen, Yao Hu, Yilong Chen, Yu Zeng, Yajing Sun, Zhiye Ying, Junhui He, Yuanyuan Qu, Donghao Lu, Fang Fang, Unnur A Valdimarsdóttir, Huan Song
Journal: The Lancet Healthy Longevity (2020)
Enhanced Risk Stratification of 21,178 Children, Adolescents, and Young Adults with Acute Lymphoblastic Leukemia (ALL) Incorporating White Blood Count (WBC), Age, and Minimal Residual Disease (MRD) at Day 8 and 29 As Continuous Variables: A Children's Oncology Group (COG) Report
Authors: Mignon L. Loh, Natalie DelRocco, Michael J Borowitz, Karen R Rabin, Patrick A Zweidler-McKay, Kelly W Maloney, Leonard A. Mattano, Eric C Larsen, Anne L Angiolillo, Reuven J Schore, Michael J Burke, Wanda L Salzer, Brent L Wood, Andrew J Carroll, Nyla A Heerema, Shalini C Reshmi, Julie M Gastier-Foster, Richard C Harvey, I-Ming L Chen, Cheryl L Willman, Naomi J Winick, William Carroll, Stephen P Hunger, Elizabeth A. Raetz, Meenakshi Devidas, John Kairalla, Kathryn G Roberts, Charles G Mullighan
Journal: Blood (2020)
Safety and Efficacy of Decitabine Plus Ipilimumab in Relapsed or Refractory MDS/AML in the Post-BMT or Transplant Naïve Settings
Authors: Jacqueline S. Garcia, Yael Flamand, Benjamin K. Tomlinson, Michael Keng, Lourdes M. Mendez, Samer Khaled, Asad Bashey, Andrew M. Brunner, Alexandra Savell, Donna Neuberg, Ilene Galinsky, Marlise R. Luskin, David P. Steensma, Martha Wadleigh, Eric S. Winer, David E. Avigan, Nicole Cullen, Scott Rodig, Livius Penter, R. Coleman Lindsley, Stephanie Andrews, Matthew S. Davids, Catherine J. Wu, Richard M. Stone, Daniel J. DeAngelo, Robert J. Soiffer
Journal: Blood (2020)
Clinical Impacts of Germline <i>DDX41</i> Mutations on Myeloid Neoplasms
Authors: Hideki Makishima, Yasuhito Nannya, June Takeda, Yukihide Momozawa, Ryunosuke Saiki, Tetsuichi Yoshizato, Yoshiko Atsuta, Yuka Iijima-Yamashita, Kenichi Yoshida, Yuichi Shiraishi, Yasunobu Nagata, Yusuke Shiozawa, Makoto Onizuka, Kenichi Chiba, Hiroko Tanaka, Nobuyuki Kakiuchi, Yotaro Ochi, Hiroo Ueno, Hidehiro Itonaga, Yoshinobu Kanda, Masashi Sanada, Ayana Kon, Yasushi Miyazaki, Keizo Horibe, Maria Creignou, Magnus Tobiasson, Hisashi Tsurumi, Senji Kasahara, Chantana Polprasert, Eva Hellstrom Lindberg, Akifumi Kondo Takaori, Toru Kiguchi, Mario Cazzola, Fumihiko Matsuda, Kazuma Ohyashiki, Jaroslaw P. Maciejewski, Torsten Haferlach, Yoichiro Kamatani, Michiaki Kubo, Satoru Miyano, Seishi Ogawa
Journal: Blood (2020)
Abstract 237: Noncanonical WNT Activation in Human Right Ventricular Heart Failure
Authors: Jonathan Edwards, Jeffrey A Brandimarto, Dong-Qing Hu, Nora Yucel, Li Li, Sunhye Jeong, Kenneth C Bedi, Hyun Tae Hwang, Mingming Zhao, Kenneth B Margulies, Daniel Bernstein, Sushma Reddy, Zoltan Arany
Journal: Circulation Research (2020)

Background: Drivers of adaptive and pathologic human right ventricular (RV) remodeling are poorly defined, but there is some evidence that WNT signaling contributes to these processes. Methods: Using a candidate gene approach, we sought to identify genes specifically expressed in RV failure by assessing the expression of 28 WNT-related genes in the RVs of three groups: human explanted nonfailing donor hearts (NF, n = 29), pre-transplant cardiomyopathy hearts with preserved RV function (pRV, n = 78), and pre-transplant cardiomyopathy hearts with RV failure (RVF, n = 35). Results: We identified the noncanonical WNT receptor ROR2 as transcriptionally strongly upregulated in RVF compared to pRV and NF (p &lt; 0.05, adjusted for multiple hypothesis testing using Benjamin-Hochberg). By western blot, ROR2 protein expression correlated to mRNA expression (R 2 = 0.41, p = 8.1 x 10-18) and increased linearly with higher right atrial to pulmonary capillary wedge ratio in RVF (R 2 =0.40, p = 3.0 x 10-5). Using trichrome, immunohistochemistry, and RNAscope, we identified preferential ROR2 mRNA and protein expression in fibrotic regions by both cardiomyocytes and noncardiomyocytes. High ROR2 expression correlated with increased expression of a known ROR2 target, the WNT/Ca2+ responsive protease calpain and its target FLNA (R 2 0.25 and 0.67, respectively, p &lt; 0.05), as well as with increased relative phosphorylation of FLNA (R 2 0.62, p &lt; 0.05), a marker of its activation by ROR2. Finally, mice with a range of RVF severity, generated by pulmonary artery constriction, demonstrated a robust increase in ROR2 and FLNA expression compared to sham-treated animals, and ROR2 and FLNA expression correlated strongly with each other (R 2 0.89, p = 6.9 x 10-5) and with increasing RV weight normalized to body weight (R 2 ~0.8, p &lt; 0.001, both). Conclusion: ROR2 expression in the RV is dramatically increased in humans and mice with severe RVF, and ROR2 expression correlates with worsening RV hemodynamics, calpain expression, FLNA cleavage, and FLNA phosphorylation. Taken together, the data reveal the robust activation of noncanonical WNT signaling in human RVF, and identify ROR2-mediated cytoskeleton protein cleavage as a potential novel target of human pathologic RV remodeling.
Mental Health Assessment of Youth with Sickle Cell Disease and Their Primary Caretakers: Baseline Depression and COVID-19 Pandemic-Associated Psychosocial Stress in a Multi-Site Study
Authors: Nancy S. Green, Deepa Manwani, Kim Smith-Whitley, Banu Aygun, Abena Appiah-Kubi, Arlene Smaldone
Journal: Blood (2020)
MicroRNA-mediated vascular intercellular communication is altered in chronic kidney disease
Authors: Andreas Zietzer, Eva Steffen, Sven Niepmann, Philip Düsing, Mohammed Rabiul Hosen, Weiyi Liu, Paul Jamme, Baravan Al-Kassou, Philipp Roger Goody, Sebastian Zimmer, Katrin S Reiners, Alexander Pfeifer, Michael Böhm, Nikos Werner, Georg Nickenig, Felix Jansen
Journal: Cardiovascular Research (2020)

Chronic kidney disease (CKD) is an independent risk factor for the development of coronary artery disease (CAD). For both, CKD and CAD, the intercellular transfer of microRNAs (miRs) through extracellular vesicles (EVs) is an important factor of disease development. Whether the combination of CAD and CKD affects endothelial function through cellular crosstalk of EV-incorporated miRs is still unknown.
Genotype-Phenotype Correlations in Patients with Myeloid Malignancies Using Explainable Artificial Intelligence
Authors: Nathan Radakovich, Luca Malcovati, Manja Meggendorfer, Mikkael A. Sekeres, Jacob Shreve, Cameron Beau Hilton, Yazan Rouphail, Wencke Walter, Stephan Hutter, Anna Gallì, Sarah Pozzi, Aaron T. Gerds, Sudipto Mukherjee, Cassandra M Kerr, Babal K. Jha, Claudia Haferlach, Jaroslaw P. Maciejewski, Torsten Haferlach, Aziz Nazha
Journal: Blood (2020)
Clinical and Genetic Findings in CTNNA1-Associated Macular Pattern Dystrophy
Authors: Alexander Tanner, Hwei Wuen Chan, Jose S. Pulido, Gavin Arno, Rola Ba-Abbad, Neringa Jurkute, Anthony G. Robson, Catherine A. Egan, Hannah Knight, Antonio Calcagni, Rachel L. Taylor, Eva Lenassi, Graeme C. Black, Anthony T. Moore, Michel Michaelides, Andrew R. Webster, Omar A. Mahroo
Journal: Ophthalmology (2020)

Macular pattern dystrophies of the retinal pigment epithelium have various causes and effects on vision, with abnormalities particularly evident on short-wavelength autofluorescence imaging. A number of genes have been implicated, frequently PRPH2. In 2015, 3 heterozygous missense variants in CTNNA1 (encoding the widely expressed α-catenin protein) were associated with butterfly-shaped pigment dystrophy: c.953T→C (p.Leu318Ser), c.1293T→G (p.Ile431Met), and c.919G→A (p.Glu307Lys).1 Herein, we describe 6 additional families with CTNNA1 missense variants (affected individuals exhibiting pattern dystrophy), corroborating the previous report.
Reduction of ARHGAP21 Alters Platelet Biogenesis <i>in Vitro</i> and Accelerates Hemostatic Response <i>In Vivo</i>
Authors: Mariana Lazarini, Vanessa Bernusso, Karla P.V Ferro, Adriana Silva Santos Duarte, Cristina Pontes Vicente, Erich V De Paula, Sara T Olalla Saad
Journal: Blood (2020)
Nelfinavir Overcomes Proteasome Inhibitor Resistance in Multiple Myeloma By Modulating Membrane Lipid Bilayer Composition and Fluidity
Authors: Andrej Besse, Lenka Besse, Sara C. Stolze, Amin Sobh, Esther A. Zaal, Alwin J van der Ham, Mario Ruiz, Santosh Phuyal, Lorina Büchler, Marc Sathianathan, Bogdan I. Florea, Jan Borén, Marcus Ståhlman, Alex Loguinov, Bart Everts, Celia R. Berkers, Marc Pilon, Hesso Farhan, Chris D. Vulpe, Herman S. Overkleeft, Christoph Driessen
Journal: Blood (2020)
Complete Hemodynamic Profiling With Pulmonary Artery Catheters in Cardiogenic Shock Is Associated With Lower In-Hospital Mortality
Authors: A Reshad Garan, Manreet Kanwar, Katherine L Thayer, Evan Whitehead, Elric Zweck, Jaime Hernandez-Montfort, Claudius Mahr, Jillian L Haywood, Neil M Harwani, Detlef Wencker, Shashank S Sinha, Esther Vorovich, Jacob Abraham, William O'Neill, Daniel Burkhoff, Navin K Kapur
Journal: JACC Heart Failure (2020)
Abstract 354: The Role of the Liver Heart Axis During Cardiac Remodeling
Authors: Soichiro Usui, Shin-ichiro Takashima, Kenji Sakata, Masa-aki Kawashiri, Masayuki Takamura
Journal: Circulation Research (2020)

Background: Hepatokine selenoprotein P (SeP) contributes to insulin resistance and hyperglycemia in patients with type 2 diabetes. Although clinical studies suggest the insulin resistance is an independent risk factor of heart failure and inhibition of SeP protects the heart from ischemia reperfusion injury, the role of SeP in pathogenesis of chronic heart failure is not well understood. Objective: We examined the role of SeP in the regulation of cardiac remodeling in response to pressure overload. Methods and Results: We measured serum SeP levels in 22 patients for heart failure with reduced ejection fraction (HFrEF; LVEF&lt;50%) and 22 normal subjects. Serum levels of SeP were significantly elevated in patients with HFrEF compared to in normal subjects (3.55 ± 0.43 vs 2.98 ± 0.43, p&lt;0.01). To examine the role of SeP in cardiac remodeling, SeP knockout (KO) and wild-type (WT) mice were subjected to pressure overload (transverse aortic constriction (TAC)) for 2 weeks. The mortality rate following TAC was significantly decreased in SeP KO mice compared to WT mice (22.5 % in KO mice (n=40) vs 52.3 % in WT mice (n=39) p&lt;0.01). LV weight/tibial length (TL) was significantly smaller in SeP KO mice than in WT mice (6.75 ± 0.24 vs 8.33 ± 0.32, p&lt;0.01). Lung weight/TL was significantly smaller in SeP KO than in WT mice (10.46 ± 0.44 vs 16.38 ± 1.12, p&lt;0.05). Interestingly, hepatic expression of SeP in WT was significantly increased by TAC. To determine whether hepatic overexpression of SeP affects TAC-induced cardiac hypertrophy, a hydrodynamic injection method was used to generate mice that overexpress SeP mRNA in the liver. Hepatic overexpression of SeP in SeP KO mice lead to a significant increase in LV weight/TL and Lung weight/TL after TAC compared to that in other SeP KO mice. Conclusions: These results suggest that serum levels of SeP were elevated in patients with heart failure with reduced ejection fraction and cardiac pressure overload induced hepatic expression of SeP in mice model. Gene deletion of SeP attenuated cardiac hypertrophy and dysfunction in response to pressure overload in mice. SeP possibly plays a pivotal role in promoting cardiac remodeling through the liver-heart axis.