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Myocardin: A novel player in atherosclerosis

  • Author Footnotes
    1 These authors contributed equally to this work.
    Xiao-Dan Xia
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medicine Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China

    Department of Hand Surgery, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421002, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Zhen Zhou
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Cardiothoracic Surgery, Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421002, China
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  • Xiao-hua Yu
    Affiliations
    Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medicine Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China
    Search for articles by this author
  • Xi-Long Zheng
    Affiliations
    Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada
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  • Chao-Ke Tang
    Correspondence
    Corresponding author.
    Affiliations
    Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medicine Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.

      Highlights

      • Myocardin plays a vital role in differentiation and development of cardiocytes and vascular smooth muscle cells (VSMCs).
      • Myocardin is a pivotal regulator on lipid metabolism and vessel inflammation.
      • Myocardin is a promising therapeutic target for atherosclerosis.

      Abstract

      Myocardin (MYOCD) the most important coactivator of serum response factor (SRF), plays a critical role specifically in the development of cardiac myocytes and vascular smooth muscle cells (VSMCs). Binding of Myocardin to the SRF on the CArG box-containing target genes can transcriptionally activate a variety of downstream muscle-specific genes, such as Sm22α, Acta2, Myh11, and several other signaling pathways. Myocardin expression represents a contractile and differentiated SMC phenotype. Loss of Myocardin, however, represents a synthetic and dedifferentiated phenotype, a hallmark in atherosclerosis. Growing evidence shows that Myocardin is involved in lipid metabolism and vascular inflammation, the primary pathogenesis of atherosclerosis. Moreover, Myocardin expression level is altered in atherosclerotic patients and animal models, suggesting more extensive and important roles for Myocardin in atherosclerosis. In the current review, we summarized recent progress on the regulation and signaling of Myocardin, and highlighted its impacts on atherosclerotic disease.

      Keywords

      Abbreviations:

      MYOCD (Myocardin), AS (atherosclerosis), SRF (serum response factor), VSMC (vascular smooth muscle cell), Mrtf-A/B (Myocardin-related transcription factors A/B), Mamstr (Mef2-activating SAP transcriptional protein), SAP domain (scaffold attachment factors A and B (SAF-A and -B), Acinus, and PIAS), MADS (MCM1, Agamous, Deficiens, SRF-box transcription factor), TAD (transactivation domain), NTD (N-terminal domain), Arp5 (actin-related protein 5), Tead (TEA domain transcription factor), Foxo (forkhead transcription factor), Cdc7 (cell division cycle 7), Mef2 (myocyte-specific enhancer factor), Nfatc3 (nuclear factor of activated T cells c3), hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1), Tet2 (ten-eleven translocation-2), TGF-β (transforming growth factor-β), URR (upstream repressor region), Klf4 (Kruppel-like factor4), PRR (platelet-derived growth factor-BB-responsive region), Pkcα (protein kinase C α), MSCs (mesenchymal stem cells), lncRNAs (long non-coding RNAs), MicroRNAs (small non-encoding RNAs), UTR (un-translated region), Abca1 (ATP-binding cassette transporter A1), RCT (reverse cholesterol transport)
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