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Cardiac fibrosis: potential therapeutic targets

  • Shuin Park
    Affiliations
    Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California

    Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, California

    Molecular, Cellular and Integrative Physiology Graduate Program, University of California, Los Angeles, Los Angeles, California
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  • Ngoc B. Nguyen
    Affiliations
    Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California

    Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, California

    Molecular, Cellular and Integrative Physiology Graduate Program, University of California, Los Angeles, Los Angeles, California
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  • Arash Pezhouman
    Affiliations
    Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California

    Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, California
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  • Reza Ardehali
    Correspondence
    Reprint requests: Reza Ardehali, MacDonald Medical Research Laboratory, Room 3760, 675 Charles E Young Dr S, Los Angeles, CA 90095.
    Affiliations
    Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California

    Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, California

    Molecular, Cellular and Integrative Physiology Graduate Program, University of California, Los Angeles, Los Angeles, California

    Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California
    Search for articles by this author
Published:March 09, 2019DOI:https://doi.org/10.1016/j.trsl.2019.03.001
      Cardiovascular disease is a leading cause of mortality in the world and is exacerbated by the presence of cardiac fibrosis, defined by the accumulation of noncontractile extracellular matrix proteins. Cardiac fibrosis is directly linked to cardiac dysfunction and increased risk of arrhythmia. Despite its prevalence, there is a lack of efficacious therapies for inhibiting or reversing cardiac fibrosis, largely due to the complexity of the cell types and signaling pathways involved. Ongoing research has aimed to understand the mechanisms of cardiac fibrosis and develop new therapies for treating scar formation. Major approaches include preventing the formation of scar tissue and replacing fibrous tissue with functional cardiomyocytes. While targeting the renin-angiotensin-aldosterone system is currently used as the standard line of therapy for heart failure, there has been increased interest in inhibiting the transforming growth factor-β signaling pathway due its established role in cardiac fibrosis. Significant advances in cell transplantation therapy and biomaterials engineering have also demonstrated potential in regenerating the myocardium. Novel techniques, such as cellular direct reprogramming, and molecular targets, such as noncoding RNAs and epigenetic modifiers, are uncovering novel therapeutic options targeting fibrosis. This review provides an overview of current approaches and discuss future directions for treating cardiac fibrosis.

      Abbreviations:

      AAV (adeno-associated viruses), AdV (adenovirus), Ang (angiotensin), CM (cardiomyocyte), CPC (cardiac progenitor cell), cTnT (cardiac troponin T), CVD (cardiovascular diseases), ECM (extracellular matrix), HF (heart failure), HFpEF (heart failure with preserved ejection fraction), HFrEF (heart failure with reduced ejection fraction), HGF (hepatocyte growth factor), hPSC (human pluripotent stem cell), LAD (left anterior descending artery), LVEDP (left ventricular end diastolic pressure), MI (myocardial infarction), MMP1 (matrix metalloproteinase-1), MSC (mesenchymal stem cell), PRR ((pro)renin receptor), RAAS (renin-angiotensin-aldosterone system), SeV (sendai virus), TGFβ (transforming growth factor β), TNFα (tumor necrosis factor α), αMHC (α-myosin heavy chain)
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