Article
Developmental Biology
Rajani M. George, Beth A. Firulli, Ram Podicheti, Douglas B. Rusch, Brandon J. Mannion, Len A. Pennacchio, Marco Osterwalder, Anthony B. Firulli
Summary: The transcription factor HAND2 is crucial in cardiogenesis and its deletion causes various heart defects. Single cell transcriptome analysis of H2CKO hearts revealed disrupted endocardial regulatory pathways. HAND2-dependent enhancers, including two for KLF2, a master regulator of shear-stress, were identified using HAND2 DNA occupancy data. Deletion of a specific enhancer caused reduced Klf2 expression in ventricular endocardium, revealing HAND2's role in endocardial gene regulatory networks and shear-stress response.
Article
Genetics & Heredity
Angelo B. Arrigo, Wenjuan Zhu, Kylia A. Williams, Carla Guzman-Moreno, Cecilia Lo, Jiuann-Huey I. Lin
Summary: The study investigates the association between genetic variants, specifically LRP1 mutations, with congenital heart disease (CHD) and its phenotypes. Through analysis of mouse models and human data, LRP1 mutations were found to be significantly associated with CHD, particularly atrioventricular septal defect and conotruncal defect. Additionally, rare damaging LRP1 mutations were observed to have a significant relationship with atrioventricular septal defect. This study provides important insights into the molecular mechanisms underlying CHD.
Article
Cell Biology
Akihiro Fukushima, Naoya Kataoka, Kazuhiro Nakamura
Summary: Oxytocinergic neurons in the PVH region innervate sympathetic premotor neurons in the rMR region to regulate BAT thermogenesis and cardiovascular functions. Defects in this pathway may lead to obesity and impaired thermoregulation.
Article
Cardiac & Cardiovascular Systems
Drayton C. Harvey, Rebecca J. Baer, Gretchen Bandoli, Christina D. Chambers, Laura L. Jelliffe-Pawlowski, S. Ram Kumar
Summary: This study examined the association between prenatal alcohol exposure and congenital heart disease (CHD) using retrospective analysis. The results showed that maternal alcohol-related diagnostic codes during pregnancy were associated with an increased risk of CHD, particularly for endocardial cushion and conotruncal defects.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Review
Cardiac & Cardiovascular Systems
Sonia Stefanovic, Heather C. Etchevers, Stephane Zaffran
Summary: Anomalies in the cardiac outflow tract (OFT) are common congenital heart defects, with the second heart field (SHF) being essential for its development. Perturbation of SHF can lead to CHDs, including anomalies of the great arteries. OFT development also depends on paracrine interactions between multiple cell types.
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
(2021)
Article
Engineering, Biomedical
Stephanie E. Lindsey, Irene E. Vignon-Clementel, Jonathan T. Butcher
Summary: Mechanical forces play a crucial role in the growth and remodeling of primitive pharyngeal arch arteries into the heart's great vessels. However, the direct correlation between hemodynamics and PAA morphogenesis has been poorly understood. A study using minimally invasive occlusion experiments in avian embryos and 3D anatomical models revealed significant changes in morphology and hemodynamics following vessel occlusion, providing insights into the dynamic vessel adaptation process.
ANNALS OF BIOMEDICAL ENGINEERING
(2021)
Article
Cardiac & Cardiovascular Systems
Marwa Mahmoud, Ian Evans, Laura Wisniewski, Yuen Tam, Claire Walsh, Simon Walker-Samuel, Paul Frankel, Peter Scambler, Ian Zachary
Summary: Research indicates a specific requirement for Bcar1 in neural crest cells, early myogenic and cardiac cells, essential for outflow tract septation, myocardialization, epithelial-to-mesenchymal transformation/cell cycle regulation, and differentiation into myogenic lineages. On the other hand, conditional knockouts of Bcar1 in differentiated smooth muscle, endothelial cells, and second heart field cells survived to term and were phenotypically normal at birth and postnatally.
CARDIOVASCULAR RESEARCH
(2022)
Article
Physiology
Leonor Parreira, Pedro Carmo, Rita Marinheiro, Dinis Mesquita, Jose Farinha, Ana Esteves, Pedro Amador, Antonio Ferreira, Marta Fonseca, Rui Caria, Pedro Adragao
Summary: In sinus rhythm, the endocardial activation duration and number of isochrones in the right ventricular outflow tract are significantly higher in patients with premature ventricular contractions compared to controls; deceleration zones and low voltage areas are more common in PVC patients. The propagation speed is lower in patients with PVCs compared to the control group.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Developmental Biology
Xuguang Nie, Christopher L. Ricupero, Kai Jiao, Peixin Yang, Jeremy J. Mao
Summary: mTOR plays a crucial role in cardiac neural crest cell development, and its disruption can lead to a spectrum of cardiac defects, including various degrees of persistent truncus arteriosus, ventricular septal defect, and ventricular wall defect.
DEVELOPMENTAL BIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Chikai Zhou, Timm Haeneke, Eduarde Rohner, Jesper Sohlmer, Polina Kameneva, Artem Artemov, Igor Adameyko, Makoto Sahara
Summary: This study investigates the mechanism by which mutations in the STRA6 gene could lead to cardiac malformations. By comparing gene expression in human and mouse embryonic hearts, it is found that STRA6 is mainly expressed in the OFT region-specific heart progenitors in human hearts. Further experiments show that STRA6 knockout in human embryonic stem cells leads to improper differentiation into smooth muscle cells derived from the mesoderm and neural crest. Additionally, an interaction between RA nuclear receptors RAR alpha/RXR alpha and the cardiogenic transcription factor TBX1 is identified.
CARDIOVASCULAR RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Claes-Goran Reibring, Maha El Shahawy, Kristina Hallberg, Brian D. Harfe, Anders Linde, Amel Gritli-Linde
Summary: BMP signaling is crucial for the differentiation of secretory ameloblasts, and this study shows that it is also required for the differentiation of maturation-stage ameloblasts. The deactivation of Bmp2 and Bmp4 genes leads to the development of dysmorphic and dysfunctional maturation-stage ameloblasts, resulting in enamel defects and abnormal cell migration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Qian Liu, Jing Yang, Zhou Bolun, Miao Pei, Bofei Ma, Qiaoli Tong, Hongning Yin, Yan Zhang, Ling You, Ruiqin Xie
Summary: The study demonstrates that compared to conventional RVOP, LBBP can enhance cardiac function, improve BNP levels, and show advantages in left atrial function in the short term.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Joshua C. Peterson, Tim P. Kelder, Marie Jose T. H. Goumans, Monique R. M. Jongbloed, Marco C. DeRuiter
Summary: Although significant progress has been made in understanding the pathophysiology of congenital heart disease (CHDs) in recent years, the developmental processes affecting the cardiac outflow tract (OFT) remain poorly understood. There is a large variation in disease phenotypes among CHDs affecting the OFT, and relating cell lineage dynamics to morphologic variation in OFT pathologies remains challenging due to technical limitations. The lack of knowledge in this area is postulated to be related to underlying cell lineage dynamics, which are not well understood.
JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE
(2021)
Article
Acoustics
Maud Regouin, Julien Mancini, Antoine Lafouge, Pierre Mace, Nathalie Fontaine, Stephanie Roussin, Jimmy Guichard, Coralie Dumont, Edwin Quarello
Summary: The objective of this study was to define quality criteria for fetal LVOT assessment and to evaluate the impact of implementing these criteria on practice. The study found that LVOT pictures were present in over 94.3% of reports, and there was no significant change in practice following the introduction of the quality criteria.
JOURNAL OF ULTRASOUND IN MEDICINE
(2023)
Article
Developmental Biology
Drayton C. Harvey, Prashan De Zoysa, Omar Toubat, Jongkyu Choi, Jahnavi Kishore, Hidekazu Tsukamoto, S. Ram Kumar
Summary: The study found that acute prenatal alcohol exposure significantly increased the incidence of congenital heart defects, especially outflow tract alignment defects. Embryos with genetic defects in the second heart field showed a much higher incidence of congenital heart defects after exposure to prenatal alcohol, especially outflow tract defects.
BIRTH DEFECTS RESEARCH
(2022)
Article
Hematology
Lisa Traeger, Steffen B. Wiegand, Andrew J. Sauer, Benjamin H. P. Corman, Kathryn M. Peneyra, Florian Wunderer, Anna Fischbach, Aranya Bagchi, Rajeev Malhotra, Warren M. Zapol, Donald B. Bloch
Summary: This study aimed to identify components of the ubiquitin system involved in ferroportin degradation. The results showed that the E1 enzyme UBA6 and the adaptor protein NDFIP1, both part of the ubiquitin pathway, regulate the degradation of ferroportin and are involved in iron homeostasis. These specific components may be promising targets for treating iron-related diseases.
Article
Hematology
Rajeev Malhotra, Christopher J. Nicholson, Dongyu Wang, Vijeta Bhambhani, Samantha Paniagua, Charles Slocum, Haakon H. Sigurslid, Christian L. Lino Cardenas, Rebecca Li, Sophie L. Boerboom, Yin-Ching Chen, Shih-Jen Hwang, Chen Yao, Fumito Ichinose, Donald B. Bloch, Mark E. Lindsay, Gregory D. Lewis, Jayashri R. Aragam, Udo Hoffmann, Gary F. Mitchell, Naomi M. Hamburg, Ramchandran S. Vasan, Emelia J. Benjamin, Martin G. Larson, Warren M. Zapol, Susan Cheng, Jason D. Roh, Christopher J. O'Donnell, Christopher Nguyen, Daniel Levy, Jennifer E. Ho
Summary: This study finds an association between ucMGP levels and arterial stiffness, as well as future HFpEF. Experimental studies using mice also support the link between Mgp heterozygosity and arterial stiffness. These findings suggest a potential role of therapeutic targeting MGP in HFpEF.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Emily S. Lau, Lindsay G. Panah, Emily K. Zern, Elizabeth E. Liu, Robyn Farrell, Mark W. Schoenike, Mayooran Namasivayam, Timothy W. Churchill, Lisa Curreri, Rajeev Malhotra, Matthew Nayor, Gregory D. Lewis, Jennifer E. Ho
Summary: This study found that arterial stiffness is higher in women with HFpEF than in men, and it is associated with abnormally steep increases in pulmonary capillary wedge pressure with exercise, particularly in women. Arterial stiffness may preferentially contribute to abnormal diastolic function during exercise in women with HFpEF compared with men.
JOURNAL OF CARDIAC FAILURE
(2022)
Article
Cell Biology
Katy Borner, Sarah A. Teichmann, Ellen M. Quardokus, James C. Gee, Kristen Browne, David Osumi-Sutherland, Bruce W. Herr, Andreas Bueckle, Hrishikesh Paul, Muzlifah Haniffa, Laura Jardine, Amy Bernard, Song-Lin Ding, Jeremy A. Miller, Shin Lin, Marc K. Halushka, Avinash Boppana, Teri A. Longacre, John Hickey, Yiing Lin, M. Todd Valerius, Yongqun He, Gloria Pryhuber, Xin Sun, Marda Jorgensen, Andrea J. Radtke, Clive Wasserfall, Fiona Ginty, Jonhan Ho, Joel Sunshine, Rebecca T. Beuschel, Maigan Brusko, Sujin Lee, Rajeev Malhotra, Sanjay Jain, Griffin Weber
Summary: This Perspective discusses collaborative efforts by 16 international consortia to create a Human Reference Atlas (HRA) that includes three-dimensional representations of anatomy linked to tables naming major anatomical structures, cell types, and biomarkers (ASCT+B), as well as examples demonstrating the practical utility of the HRA.
NATURE CELL BIOLOGY
(2021)
Article
Critical Care Medicine
Annelise M. Kulpanowski, William A. Copen, Brandon L. Hancock, Eric S. Rosenthal, David A. Schoenfeld, Jacob A. Dodelson, Brian L. Edlow, W. Taylor Kimberly, Edilberto Amorim, M. Brandon Westover, Ming Ming Ning, Pamela W. Schaefer, Rajeev Malhotra, Joseph T. Giacino, David M. Greer, Ona Wu
Summary: Studies show that patients with substance-related cardiac arrests (SRCA) are more likely to develop severe cerebral edema and brain death compared to non-SRCA patients. However, there were no significant differences in discharge outcomes or survival between the two groups, potentially due to the higher rate of withdrawal of life-sustaining treatment in the non-SRCA group.
Review
Transplantation
Wen Wen, Ignacio Portales-Castillo, Rituvanthikaa Seethapathy, Scott Krinsky, Daniela Kroshinsky, Sahir Kalim, Jeremy Goverman, Rosalynn M. Nazarian, Vipul Chitalia, Rajeev Malhotra, Rafael Kramann, Cindy K. Malhotra, Sagar U. Nigwekar
Summary: This study evaluated the effects and safety of intravenous sodium thiosulphate (STS) for vascular calcification (VC) in patients with chronic kidney disease (CKD). The results showed that STS treatment could attenuate the progression of VC and arterial stiffness, with no significant adverse effects observed.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Biochemistry & Molecular Biology
Simone Redaelli, Aurora Magliocca, Rajeev Malhotra, Giuseppe Ristagno, Giuseppe Citerio, Giacomo Bellani, Lorenzo Berra, Emanuele Rezoagli
Summary: Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that has been approved by the FDA for treating persistent pulmonary hypertension in newborns. While it has shown promising effects in preclinical studies, there is a lack of high quality evidence for its use in clinical settings. Various clinical applications have been suggested, but more randomized clinical trials are needed to determine the specific therapeutic roles of iNO.
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2022)
Article
Cardiac & Cardiovascular Systems
Mayooran W. Namasivayam, Emily M. Lau, Emily A. Zern, Mark F. Schoenike, Kathryn M. Hardin, John Sbarbaro, Thomas Cunningham, Robyn R. Farrell, Jennifer C. Rouvina, Alyssa Kowal, Rohan E. Bhat, Liana Brooks, Matthew D. Nayor, Ravi V. Shah, Jennifer E. Ho, Rajeev Malhotra, Gregory D. Lewis
Summary: In this study, the hemodynamic correlates of inducible blood pressure pulsatility with exercise were evaluated in patients with HFpEF. The results showed that blood pressure pulsatility in HFpEF is associated with arterial stiffness and adverse cardiovascular outcomes.
JACC-HEART FAILURE
(2022)
Letter
Cardiac & Cardiovascular Systems
Matthew Nayor, Ariel Chernofsky, Patricia E. Miller, Nicole L. Spartano, Venkatesh L. Murthy, Rajeev Malhotra, Nicholas E. Houstis, Joanne M. Murabito, Clary B. Clish, Martin G. Larson, Ramachandran S. Vasan, Ravi V. Shah, Gregory D. Lewis
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2022)
Review
Critical Care Medicine
Davide Signori, Aurora Magliocca, Kei Hayashida, Jan A. Graw, Rajeev Malhotra, Giacomo Bellani, Lorenzo Berra, Emanuele Rezoagli
Summary: Nitric oxide (NO) plays a crucial role in human life, being involved in both organ physiology and pathophysiology. This review aims to elucidate the mechanisms of NO in the respiratory and cardio-cerebrovascular systems under healthy or dysfunctional endothelium. It covers the production and effects of endogenous NO, as well as the disturbances related to NO depletion and excess. The potential therapeutic role of exogenous NO and the importance of NO in various clinical conditions are also discussed.
INTENSIVE CARE MEDICINE EXPERIMENTAL
(2022)
Article
Cardiac & Cardiovascular Systems
Ravi Shah, Patricia Miller, Laura A. Colangelo, Ariel Chernofsky, Nicholas E. Houstis, Rajeev Malhotra, Raghava S. Velagaleti, David R. Jacobs, Kelley Pettee Gabriel, Jared P. Reis, Donald M. Lloyd-Jones, Clary B. Clish, Martin G. Larson, Ramachandran S. Vasan, Venkatesh L. Murthy, Gregory D. Lewis, Matthew Nayor
Summary: This study aimed to develop a blood-based biomarker for cardiorespiratory fitness and explore its application in predicting the risk of cardiovascular disease and mortality. The researchers found that this blood biomarker had a high correlation with cardiorespiratory fitness and could predict the risk of cardiovascular disease and mortality in young adults.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Review
Hematology
Nadia R. Sutton, Rajeev Malhotra, Cynthia St. Hilaire, Elena Aikawa, Roger S. Blumenthal, Grace Gackenbach, Parag Goyal, Adam Johnson, Sagar U. Nigwekar, Catherine M. Shanahan, Dwight A. Towler, Brooke N. Wolford, Yabing Chen
Summary: Cardiovascular disease is the leading cause of death globally, particularly in individuals over the age of 65, with myocardial infarction and stroke being the primary contributors. The development of vascular aging and vascular calcification with aging is not fully understood, but is believed to be influenced by genetic risk, environmental factors, and the ability of vascular smooth muscle cells to acquire an osteogenic phenotype. Understanding the molecular mechanisms behind age-associated vascular pathology may lead to strategies for promoting healthy vascular aging. This article provides a summary of current knowledge on age-associated vascular disease, with a focus on vascular calcification.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tslil Ast, Hong Wang, Eizo Marutani, Fumiaki Nagashima, Rajeev Malhotra, Fumito Ichinose, Vamsi K. Mootha
Summary: Friedreich's ataxia (FA) is a devastating neurodegenerative disease, and oxygen is a key environmental variable that can modify its pathogenesis. This study evaluated seven hypoxia-inspired regimens in a mouse model of FA and found that an intermittent hypoxia regimen was harmful, while mild chronic hypoxia delayed the onset of ataxia. Excitingly, chronic, continuous 11% oxygen breathing could rapidly reverse ataxia. These findings highlight the potential and limitations of hypoxia-inspired regimens for FA and emphasize the need for further pre-clinical optimization before translation to humans.
HUMAN MOLECULAR GENETICS
(2023)
Editorial Material
Biology
Kuldeep Singh, Rajeev Malhotra
Summary: The accumulation of iron as one grows older may hinder the positive effects of hormone replacement therapy on cardiovascular disease in women during late postmenopause.
Article
Multidisciplinary Sciences
Avinash Boppana, Sujin Lee, Rajeev Malhotra, Marc Halushka, Katherine S. Gustilo, Ellen M. Quardokus, Bruce W. W. Herr II, Katy Borner, Griffin M. Weber
Summary: More than 150 scientists from 17 consortia are collaborating on an international project to build a Human Reference Atlas, which maps all 37 trillion cells in the healthy adult human body. The project has released the first open and comprehensive database of the adult human blood vasculature, called the Human Reference Atlas-Vasculature Common Coordinate Framework (HRA-VCCF). It includes 993 vessels and their branching connections, 10 cell types, and 10 biomarkers.
Review
Developmental Biology
Cheng Shi, Pengfei Jiao, Zhiyi Chen, Lan Ma, Siyue Yao
Summary: This review discusses the molecular etiology of congenital craniofacial abnormalities, with a focus on the role and mechanism of noncoding RNAs in regulating craniofacial development. Aberrant expression of noncoding RNAs has been implicated in the pathogenesis of craniofacial abnormalities, providing potential therapeutic targets.
DEVELOPMENTAL BIOLOGY
(2024)
Article
Developmental Biology
Hideru Togashi, Steven Ray Davis, Makoto Sato
Summary: Tile patterns, regulated by cell adhesion molecules, are regular arrangements of cells that play important functional roles in multicellular organisms. The physical constraints and cell adhesion regulate both cell shape and tissue morphogenesis.
DEVELOPMENTAL BIOLOGY
(2024)
Article
Developmental Biology
Armen Khanbabei, Lina Segura, Cynthia Petrossian, Aaron Lemus, Ithan Cano, Courtney Frazier, Armen Halajyan, Donnie Ca, Mariano Loza-Coll
Summary: This article investigates the genetic regulatory mechanisms of Drosophila intestinal stem cells. The study found that most target genes co-regulated by Esg and STAT show a consistent gene expression pattern. However, manipulating these validated targets in vivo rarely replicated the effects of manipulating Esg and STAT, suggesting the presence of complex genetic interactions among the downstream targets of these two master regulator genes.
DEVELOPMENTAL BIOLOGY
(2024)
Article
Developmental Biology
Bayley J. Waters, Zoe R. Birman, Matthew R. Wagner, Julia Lemanski, Barak Blum
Summary: Researchers found that conditional deletion of Robo2 in adult mice led to a significant loss of islet architecture without affecting beta cell identity or function, suggesting that Robo2 plays a role in actively maintaining adult islet architecture. Understanding the factors required for islet architecture maintenance is crucial for developing future diabetes therapies.
DEVELOPMENTAL BIOLOGY
(2024)
Article
Developmental Biology
Rhiannon Clements, Tyler Smith, Luke Cowart, Jennifer Zhumi, Alan Sherrod, Aidan Cahill, Ginger L. Hunter
Summary: Cell protrusions play a crucial role in regulating cell activities during development. By studying the regulation mechanism in fruit fly sensory bristle patterning, it was found that Myosin XV is essential for the dynamics of signaling filopodia and promotes long-range Notch signaling.
DEVELOPMENTAL BIOLOGY
(2024)
Article
Developmental Biology
Margaret Keating, Ryan Hagle, Daniel Osorio-Mendez, Anjelica Rodriguez-Parks, Sarah I. Almutawa, Junsu Kang
Summary: Knock-in reporter (KI) animals are essential for studying gene expression in biomedical research. This study developed a new strategy using minicircle technology and a minimal promoter to enhance knock-in events and establish stable KI transgenic reporter lines. The study also highlighted the importance of selecting the proper KI line due to potential inappropriate influence of genome editing on reporter gene expression.
DEVELOPMENTAL BIOLOGY
(2024)
Article
Developmental Biology
Christian Altbuerger, Meta Rath, Daniel Armbruster, Wolfgang Driever
Summary: This study reveals that Neurog1 and Olig2 transcription factors have differential requirements for the development of dopaminergic neurons, and they integrate local patterning signals and Notch neurogenic selection signaling to specify the progenitor population and initiate neurogenesis and differentiation.
DEVELOPMENTAL BIOLOGY
(2024)
