• Dominant form of heart failure caused by

    From ScienceDaily@1:317/3 to All on Tue Mar 22 22:30:46 2022
    Dominant form of heart failure caused by metabolic-immune interaction,
    review article suggests

    Date:
    March 22, 2022
    Source:
    UT Southwestern Medical Center
    Summary:
    The dominant form of heart failure worldwide appears to be caused
    by a strong, bidirectional interaction between the body's response
    to metabolic stress and the immune system, according to a review
    article.

    The article argues for more research into this root cause to
    develop truly effective treatments.



    FULL STORY ==========================================================================
    The dominant form of heart failure worldwide appears to be caused by
    a strong, bidirectional interaction between the body's response to
    metabolic stress and the immune system, according to a review article
    written by UT Southwestern researchers and colleagues. The article,
    published in Nature Cardiovascular Research, argues for more research
    into this root cause to develop truly effective treatments.


    ========================================================================== "Heart failure with preserved ejection fraction affects millions of
    people around the globe, but we currently have little to offer these
    patients because the mechanisms behind it have been unknown. It's been
    called the single greatest unmet need in cardiovascular medicine,"
    said the article's senior author Joseph Hill, M.D., Ph.D., Professor
    of Internal Medicine and Molecular Biology and Chief of Cardiology
    at UT Southwestern. "We now have insight into this condition that we
    didn't have even five years ago, observations that could lead to viable clinical targets." Dr. Hill explained that heart failure -- the heart's inability to effectively pump blood -- comes in two broad types: heart
    failure with reduced ejection fraction (HFrEF), in which the amount of
    blood that leaves the heart with each beat declines, and heart failure
    with preserved ejection fraction (HFpEF), in which the heart is unable to
    fill with blood to capacity. While HFrEF has long been the most common
    form, HFpEF -- which is associated with obesity, diabetes, and other
    components of metabolic syndrome -- has grown in prevalence over the
    last several decades and overtaken HFrEF as the most common form.

    Numerous treatments exist for various types of HFrEF, but these
    interventions have no discernible effect on HFpEF. This is because
    the two conditions are caused by different underlying mechanisms, said
    Dr. Hill, a topic that his lab has studied for years. Although HFpEF can
    be improved through weight loss, losing weight is something that many individuals struggle with, he added, prompting the need for treatments.

    In the review article, Hill and his colleagues outline findings made
    over the past several years that point to joint metabolic and immune dysfunction as the root cause of HFpEF. For example, fat tissue secretes inflammatory molecules that migrate to the heart, recruiting immune
    cells evident in heart biopsy samples from individuals with HFpEF. At
    the same time, heart toxicity caused by overuse of fatty acids as fuel
    in individuals with metabolic syndrome appears to stimulate an immune
    response, leading to a vicious cycle.

    Crosstalk between fat tissue, the immune system, and the heart appears to amplify both immune and metabolic stress, ultimately causing the heart to
    fail over time. But how this crosstalk occurs, the effects it produces,
    and how to block them remain unclear, Dr. Hill said. Research into this
    new field of immunometabolism is shedding some light on these questions,
    but more research will be necessary to produce effective interventions
    for HFpEF patients, he added.

    "Research from our lab and others is raising possibilities of therapeutic targets that need to be investigated," Dr. Hill said. "There's a
    reasonable chance that we could have therapies available for this
    intractable condition within the next decade." U.S. News and World
    Reportranks UT Southwestern as the No.1 hospital in Texas for Cardiology
    and Heart Surgery and No.11 in the nation.

    Dr. Hill holds the James T. Willerson, M.D., Distinguished Chair in Cardiovascular Diseases and the Frank M. Ryburn Jr. Chair in Heart
    Research.

    Thomas G. Gillette, Ph.D., Associate Professor of Internal Medicine at
    UT Southwestern, contributed to the review article.

    This work was supported by grants from the DZHK (German Centre for Cardiovascular Research); the Deutsche Forschungsgemeinschaft (German
    Research Foundation, SFB-1470-A02), IMI2-CARDIATEAM (no. 821508); the Netherlands Cardiovascular Research Initiative, Dutch Cardiovascular
    Alliance CVON2016- Early HFPEF, 2015-10, CVON She-PREDICTS, no. 2017-21; National Institutes of Health (HL144477, HL122309, HL126012, HL128215, HL120732, HL147933 and HL155765), and the American Heart Association (19TPA34910006).


    ========================================================================== Story Source: Materials provided by UT_Southwestern_Medical_Center. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Gabriele G. Schiattarella, Pilar Alcaide, Gianluigi Condorelli,
    Thomas G.

    Gillette, Stephane Heymans, Elizabeth A. V. Jones, Marinos
    Kallikourdis, Andrew Lichtman, Federica Marelli-Berg, Sanjiv
    J. Shah, Edward B. Thorp, Joseph A. Hill. Immunometabolic
    mechanisms of heart failure with preserved ejection
    fraction. Nature Cardiovascular Research, 2022; 1 (3): 211 DOI:
    10.1038/s44161-022-00032-w ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220322191215.htm

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