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Tag: National Heart

  • Small proteins in heart play big role

    Small proteins in heart play big role

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    BYLINE: Beth Miller

    Newswise — A heartbeat is a carefully coordinated series of electrical signals led by sodium ion channels, which tell the heart when to contract and to relax. Any disruption to these signals may lead to cardiac diseases such as an irregular heartbeat, or arrhythmia. Two researchers at Washington University in St. Louis have taken a closer look at this process at the molecular level and have found what may provide new insights into different heart conditions and how to develop better therapies.

    Jonathan Silva, the Dennis & Barbara Kessler Career Development Associate Professor at the McKelvey School of Engineering, and Jeanne Nerbonne, Alumni Endowed Professor of Molecular Biology & Pharmacology in Medicine and Developmental Biology at the School of Medicine, and their labs found distinct effects of novel proteins, known as intracellular fibroblast growth factors (iFGF), on the regulation of the kinetics of cardiac sodium channel gating. Their results were published in the Journal of General Physiology March 21.

    Intracellular fibroblast growth factors are small proteins that are known to bind to sodium channels and to influence how these channels open and close, or “gate.” The gating properties of cardiac sodium channels affect how the electromechanical propagate through the heart. In addition, drugs interact differently with the sodium channels in different gating (i.e., open and closed) states, Silva said.

    The team sought to determine how one intracellular fibroblast growth factor, iFGF12, works in a healthy human heart by observing how the iFGFs change the sodium channel at the molecular level. Nerbonne’s lab generated a mouse model with iFGF12 to observe how it modulates the sodium channel in myocytes. Using electrophysiology methods, they found that it modulated the channel differently than the comparable iFGF in the mouse heart and changed the properties of the sodium current.

    “One of the reasons we want to define how the iFGFs and other sodium channel accessory proteins affect channel properties at the molecular level is that we know from previous work that the protein components of functional channels influence the pharmacology of these channels,” said Nerbonne, who also is the director of the Center for Cardiovascular Research. “These channels are potential therapeutic targets for people with arrhythmias.”

    Silva’s lab looked at how the iFGF affects channel function through methods they have developed to watch the voltage sensing domains.

    “We looked at how these subunits affect native cell electrophysiology, and that’s an exciting part of our collaboration with the Nerbonne lab,” Silva said. “We were able to determine how these subunits change the channel at the molecular level to cause those cell-level effects.”

    Going forward, the team plans to take a closer look at how different drugs interact with sodium channels that have different iFGF compositions.

    ***

    Originally published by the McKelvey School of Engineering.

    Angsutararux P, Dutta AK, Marras M, Abella C, Mellor RL, Shi J, Nerbonne JM, Silva JR. Differential regulation of cardiac sodium channels by intracellular fibroblast growth factors. Journal of General Physiology, March 21, 2023. https://doi.org/10.1085/jgp.202213300

    This research was supported by the National Institutes of Health’s National Heart, Lung, and Blood Institute (R01 142520 and R01 HL150637); the NIH National Center for Research Resources (UL1 RR024992) and the Children’s Discovery Institute Pediatric Disease Mouse Models Core at Washington University.

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    Washington University in St. Louis

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  • With $13M, UIC scientists will study lung inflammation mechanisms

    With $13M, UIC scientists will study lung inflammation mechanisms

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    Newswise — Researchers from the University of Illinois Chicago hope to learn more about how the human immune system is regulated by the endothelium in lung tissue, thanks to a $13 million, multi-project Program Project Grant award from the National Heart, Lung, and Blood Institute.

    The researchers hope that the projects will lead to new avenues for research and treatments to help patients who suffer from conditions like chronic obstructive pulmonary disorder, pulmonary fibrosis and acute respiratory distress disorder, a common and serious complication of COVID-19.

    Conditions like these are known to be exacerbated by the body’s own immune response, such as when the inflammation meant to fight infections or heal injuries spirals out of control and winds up inflicting harm.

    The researchers think that these inflammatory conditions may be common in the lungs because of unique endothelial cells, which line blood vessels and shield the lungs from trauma and bacterial or viral infections.

    “Targeted therapies remain an urgent unmet need. It is now becoming increasingly clear that the lung endothelium is a complex monolayer, an organ itself,” said Dolly Mehta, UIC professor and interim head of the Department of Pharmacology and Regenerative Medicine at the College of Medicine and the program director for the grant.  

    “Studying this enigmatic immune regulatory function of lung endothelium is crucial for understanding how endothelial cells control immunity and defensive function of the lungs,” she said.

    The research team consists of six investigators who will lead three separate project grants and three separate cores.

    Mehta is also the principal investigator for one of the projects, for $2.2 million, which supports research on a protein receptor in endothelial cells that promotes lung integrity.

    Asrar Malik, professor of pharmacology and regenerative medicine, and Dr. Jalees Rehman, professor and head of the Department of Biochemistry and Molecular Genetics, will lead the other two project grants.

    Malik’s lab will look at an enzyme called E3 ligase that influences the integrity of the lining of the blood vessels and the genes that activate the enzyme. Rehman’s lab will look at how mitochondria in endothelial cells can be leveraged to prevent out-of-control inflammation. The awards are $1.8 million and $2.2 million, respectively.

    “We know that in tissues like those found in the lung, heart and brain, the blood vessels present a unique and complicated immune environment, and we know that there is an interconnectedness between all the many cellular processes. The idea of this multi-project grant is to help create an infrastructure for collaboration among researchers looking at these various mechanisms,” Mehta said.

    Konstantinos Chronis, assistant professor of biochemistry and molecular genetics, will lead the project’s epigenetics and transcriptomics core. Gary Mo, assistant professor of pharmacology and regenerative medicine, will lead the cellular imaging core. Yoshikazu Tsukasaki, a research assistant professor also from the department of pharmacology and regenerative medicine, will lead the intravital imaging and physiology core.

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    University of Illinois Chicago

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  • Rutgers Researchers to Study the Impact of Multiple Health Conditions on Medication Outcomes in Older Adults

    Rutgers Researchers to Study the Impact of Multiple Health Conditions on Medication Outcomes in Older Adults

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    Newswise — The National Institutes of Health has awarded Rutgers a $3.5 million grant to conduct a five-year study exploring the impact medications have on older adults with multiple medical conditions.

    The goal of researchers from Rutgers Center for Pharmacoepidemiology and Treatment Science (PETS) is to provide patients with multiple chronic conditions, caregivers and health care providers with information needed to make informed treatment decisions.

    “Unfortunately, most clinical trials of medications do not include patients with multimorbidity, which means that there is little data available about the risks and benefits of medications in this population,” said Chintan Dave, assistant director at PETS and the principal investigator of the National Heart, Lung and Blood Institute grant-backed project. “This lack of information makes it difficult for health care providers to make informed decisions about treating patients with multiple medical conditions.”

    Multimorbidity is a common issue for older adults, according to researchers. In the U.S., more than two thirds of adults over the age of 65 have multiple chronic conditions, which can lead to higher health care costs and increased risk of negative health outcomes, including death.

    “With over 36 million older adults in the U.S. affected by multimorbidity, this is a pressing issue that requires immediate attention,” said Dave, who also is a core faculty member of the Rutgers Institute for Health, Health Care Policy and Aging Research (IFH) and an assistant professor with Rutgers Ernest Mario School of Pharmacy.

    Dave and his colleagues will use data from more than 23 million patients to learn how having multiple conditions affects the benefits and risks of medications, representing the first effort to systematically evaluate the impact of multimorbidity on medication related outcomes. Specifically, researchers will examine medication use and outcomes in three highly prevalent chronic conditions: Type 2 diabetes, atrial fibrillation and atherosclerotic cardiovascular disease.

    Coinvestigators involved in the study include Brian Strom, the chancellor of Rutgers Biomedical and Health Sciences; Tobias Gerhard, interim director of IFH and director of PETS; Jason Roy, a professor of biostatistics and chair of the Department of Biostatistics and Epidemiology at the Rutgers School of Public Health; Soko Setoguchi, a core faculty member at PETS and IFH, professor of medicine at Rutgers Robert Wood Johnson Medical School and professor of epidemiology at Rutgers School of Public Health; and Melissa Wei, an assistant professor of medicine in residence at the David Geffen School of Medicine at University of California, Los Angeles.

    The grant was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R01HL163163. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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    Rutgers University-New Brunswick

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  • Tufts University Researchers Find Link Between Foods Scored Higher By New Nutrient Profiling System and Better Long-Term Health Outcomes

    Tufts University Researchers Find Link Between Foods Scored Higher By New Nutrient Profiling System and Better Long-Term Health Outcomes

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    Newswise — The idea that what we eat directly affects our health is ancient; Hippocrates recognized this as far back as 400 B.C. But, identifying healthier foods in the supermarket aisle and on restaurant menus is increasingly challenging. Now, researchers at the Friedman School of Nutrition Science and Policy at Tufts have shown that a holistic food profiling system, Food Compass, identifies better overall health and lower risk for mortality.  

    In a paper published in Nature Communications on November 22, researchers assessed whether adults who ate more foods with higher Food Compass scores had better long-term health outcomes and found that they did.

    Introduced in 2021, Food Compass provides a holistic measure of the overall nutritional value of a food, beverage, or mixed meal. It measures 9 domains of each item, such as nutrient ratios, food-based ingredients, vitamins, minerals, extent of processing, and additives. Based on scores of 10,000 commonly consumed products in the U.S., researchers recommend foods with scores of 70 or above as foods to encourage; foods with scores of 31-69 to be eaten in moderation; and anything that scores 30 or below to be consumed sparingly. For this new study, Food Compass was used to score a person’s entire diet, based on the Food Compass scores of all the foods and beverages they regularly consume.

    “A nutrient profiling system is intended to be an objective measure of how healthy a food is. If it’s achieving its purpose, then individuals who eat more foods with higher scores should have better health,” said Meghan O’Hearn, a doctoral candidate at the Friedman School and the study’s lead author.

    For this validation study, researchers used nationally representative dietary records and health data from 47,999 U.S. adults aged 20-85 who were enrolled between 1999-2018 in the National Health and Nutrition Examination Survey (NHANES). Deaths were determined through linkage with the National Death Index (NDI).

    Overall, researchers found that the mean Food Compass score for the diets of the nearly 50,000 subjects was only 35.5 out of 100, well below ideal. “One of the most alarming discoveries was just how poor the national average diet is,” said O’Hearn. “This is a call for actions to improve diet quality in the United States.”

    When people’s Food Compass diet scores were assessed against health outcomes, multiple significant relationships were seen, even adjusting for other risk factors like age, sex, race, ethnicity, education, income, smoking, alcohol intake, physical activity, and diabetes status. A higher Food Compass diet score was associated with lower blood pressure, blood sugar, blood cholesterol, body mass index, and hemoglobin A1c levels; and lower prevalence of metabolic syndrome and cancer. A higher Food Compass diet score was also associated with lower risk of mortality: for each 10-point increase, there was a 7 percent lower risk of death from all causes.

    “When searching for healthy foods and drinks, it can be a bit of a wild west,” said Dariush Mozaffarian, Jean Mayer Professor of Nutrition and dean for policy at the Friedman School. “Our findings support the validity of Food Compass as a tool to guide consumer decisions, as well as industry reformulations and public health strategies to identify and encourage healthier foods and beverages.”

    Compared to existing nutrient profiling systems, Food Compass provides a more innovative and comprehensive assessment of nutritional quality, researchers say. For example, rather than measuring levels of dietary fats, sodium, or fiber in isolation, it takes a more nuanced and holistic view, evaluating the ratio of saturated to unsaturated fat; sodium to potassium; and carbohydrate to fiber. 

    Food Compass also boosts scores for ingredients shown to have protective effects on health, like fruits, non-starchy vegetables, beans and legumes, whole grains, nuts and seeds, seafood, yogurt, and plant oils; and lowers scores for less healthful ingredients like refined grains, red and processed meat, and ultra-processed foods and additives.

    Researchers designed Food Compass with the ever-evolving field of nutrition science in mind, and their multidisciplinary team—comprised of researchers with expertise in epidemiology, medicine, economics, and biomolecular nutrition—will continue to evaluate and adapt the tool based on the most cutting-edge nutrition research.

    “We know Food Compass is not perfect,” said Mozaffarian. “But, it provides a more comprehensive, holistic rating of a food’s nutritional value than existing systems, and these new findings support its validity by showing it predicts better health.”

    These findings are timely given the release of the new U.S. National Strategy on Hunger, Nutrition and Health. One pillar of this strategy is to “empower all consumers to make and have access to healthy choices” through measures such as updating food labeling and making it easier to interpret, creating healthier food environments, and creating a healthier food supply.

    “This study further validates Food Compass as a useful tool for defining healthy foods. We hope the Food Compass algorithm—publicly available to all—can help guide front-of-pack labeling; procurement choices in workplace, hospital, and school cafeterias; incentive programs for healthier eating in healthcare and federal nutrition programs; industry reformulations; and government policies around food,” said O’Hearn.  

    Researchers plan to work on a simplified version that requires fewer nutrient inputs, as well as versions tailored to specific conditions such as diabetes and pregnancy or to other nations’ populations. The research team is also interested in adding Food Compass domains based on other aspects of foods, such as environmental sustainability, social justice, or animal welfare.

    “We look forward to continuing to find ways to improve the Food Compass system, and to get it to more users to help clear up confusion about healthier choices,” said Mozaffarian.

    Research reported in this article was supported by the National Institutes of Health’s National Heart, Lung, and Blood Institute under award number 2R01HL115189 and Vail Innovative Global Research. Complete information on authors, funders, and conflicts of interest is available in the published paper.

    The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.

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    Tufts University

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