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SMYD2 regulates vascular smooth muscle cell phenotypic switching and intimal hyperplasia via interaction with myocardin

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Abstract

The SET and MYND domain-containing protein 2 (SMYD2) is a histone lysine methyltransferase that has been reported to regulate carcinogenesis and inflammation. However, its role in vascular smooth muscle cell (VSMC) homeostasis and vascular diseases has not been determined. Here, we investigated the role of SMYD2 in VSMC phenotypic modulation and vascular intimal hyperplasia and elucidated the underlying mechanism. We observed that SMYD2 expression was downregulated in injured carotid arteries in mice and phenotypically modulated VSMCs in vitro. Using an SMC-specific SMYD2 knockout mouse model, we found that SMYD2 ablation in VSMCs exacerbated neointima formation after vascular injury in vivo. Conversely, SMYD2 overexpression inhibited VSMC proliferation and migration in vitro and attenuated arterial narrowing in injured vessels in mice. SMYD2 downregulation promoted VSMC phenotypic switching accompanied with enhanced proliferation and migration. Mechanistically, genome-wide transcriptome analysis and loss/gain-of-function studies revealed that SMYD2 up-regulated VSMC contractile gene expression and suppressed VSMC proliferation and migration, in part, by promoting expression and transactivation of the master transcription cofactor myocardin. In addition, myocardin directly interacted with SMYD2, thereby facilitating SMYD2 recruitment to the CArG regions of SMC contractile gene promoters and leading to an open chromatin status around SMC contractile gene promoters via SMYD2-mediated H3K4 methylation. Hence, we conclude that SMYD2 is a novel regulator of VSMC contractile phenotype and intimal hyperplasia via a myocardin-dependent epigenetic regulatory mechanism.

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Data availability

All data associated with this study are present in the paper or the Supplementary Materials. RNA-seq data are accessible at the GEO under accession number: GSE161004. Any additional information for this study is available by contacting the corresponding authors upon reasonable request.

Abbreviations

CArG:

CC(A/T)6GG

ChIP:

Quantitative chromatin immunoprecipitation

ChIP-qPCR:

Chromatin immunoprecipitation-quantitative PCR

CT:

C-terminal

H3K36:

Histone H3 at lysine 36

H3K4:

Histone H3 at lysine 4

H4K20:

Histone H4 at lysine 20

HASMC:

Human aortic smooth muscle cell

LCA:

Left common carotid artery

MRTF-A/B:

Myocardin-related transcription factor A/B

PDGF-BB:

Platelet-derived growth factor BB

PLA:

Proximity ligation assay

RCA:

Right common carotid artery

SMYD2:

SET and MYND domain-containing protein 2

SMYD2SMC − / − :

SMC-specific SMYD2-deficient mice

SMYD2fl/fl :

SMYD2 homozygous floxed mice

SRF:

Serum response factor

TAD:

Transcription activation domain

VSMC:

Vascular smooth muscle cell

References

  1. Bennett MR, Sinha S, Owens GK (2016) Vascular smooth muscle cells in atherosclerosis. Circ Res 118:692–702. https://doi.org/10.1161/CIRCRESAHA.115.306361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Gomez D, Owens GK (2012) Smooth muscle cell phenotypic switching in atherosclerosis. Cardiovasc Res 95:156–164. https://doi.org/10.1093/cvr/cvs115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Alexander MR, Owens GK (2012) Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease. Annu Rev Physiol 74:13–40. https://doi.org/10.1146/annurev-physiol-012110-142315

    Article  CAS  PubMed  Google Scholar 

  4. Yoshida T et al (2003) Myocardin is a key regulator of CArG-dependent transcription of multiple smooth muscle marker genes. Circ Res 92:856–864. https://doi.org/10.1161/01.res.0000068405.49081.09

    Article  CAS  PubMed  Google Scholar 

  5. Miano JM, Long X, Fujiwara K (2007) Serum response factor: master regulator of the actin cytoskeleton and contractile apparatus. Am J Physiol Cell Physiol 292:C70-81. https://doi.org/10.1152/ajpcell.00386.2006

    Article  CAS  PubMed  Google Scholar 

  6. Miano JM (2015) Myocardin in biology and disease. J Biomed Res 29:3–19. https://doi.org/10.7555/jbr.29.20140151

    Article  CAS  PubMed  Google Scholar 

  7. Lockman K, Taylor JM, Mack CP (2007) The histone demethylase, Jmjd1a, interacts with the myocardin factors to regulate SMC differentiation marker gene expression. Circ Res 101:e115-123. https://doi.org/10.1161/circresaha.107.164178

    Article  CAS  PubMed  Google Scholar 

  8. Gan Q et al (2011) WD repeat-containing protein 5, a ubiquitously expressed histone methyltransferase adaptor protein, regulates smooth muscle cell-selective gene activation through interaction with pituitary homeobox 2. J Biol Chem 286:21853–21864. https://doi.org/10.1074/jbc.M111.233098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Liu R et al (2013) Ten-eleven translocation-2 (TET2) is a master regulator of smooth muscle cell plasticity. Circulation 128:2047–2057. https://doi.org/10.1161/CIRCULATIONAHA.113.002887

    Article  PubMed  PubMed Central  Google Scholar 

  10. Barrero MJ, Boue S, Izpisua Belmonte JC (2010) Epigenetic mechanisms that regulate cell identity. Cell Stem Cell 7:565–570. https://doi.org/10.1016/j.stem.2010.10.009

    Article  CAS  PubMed  Google Scholar 

  11. Bauer AJ, Martin KA (2017) Coordinating regulation of gene expression in cardiovascular disease: interactions between chromatin modifiers and transcription factors. Front Cardiovasc Med 4:19. https://doi.org/10.3389/fcvm.2017.00019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gomez D, Swiatlowska P, Owens GK (2015) Epigenetic control of smooth muscle cell identity and lineage memory. Arterioscler Thromb Vasc Biol 35:2508–2516. https://doi.org/10.1161/atvbaha.115.305044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Liu R, Leslie KL, Martin KA (2015) Epigenetic regulation of smooth muscle cell plasticity. Biochem Biophys Acta 1849:448–453. https://doi.org/10.1016/j.bbagrm.2014.06.004

    Article  CAS  PubMed  Google Scholar 

  14. Villeneuve LM et al (2008) Epigenetic histone H3 lysine 9 methylation in metabolic memory and inflammatory phenotype of vascular smooth muscle cells in diabetes. Proc Natl Acad Sci U S A 105:9047–9052. https://doi.org/10.1073/pnas.0803623105

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ahmed ASI et al (2018) Long noncoding RNA NEAT1 (nuclear paraspeckle assembly transcript 1) is critical for phenotypic switching of vascular smooth muscle cells. Proc Natl Acad Sci U S A 115:E8660–E8667. https://doi.org/10.1073/pnas.1803725115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Brown MA, Sims RJ 3rd, Gottlieb PD, Tucker PW (2006) Identification and characterization of SMYD2: a split SET/MYND domain-containing histone H3 lysine 36-specific methyltransferase that interacts with the Sin3 histone deacetylase complex. Mol Cancer 5:26. https://doi.org/10.1186/1476-4598-5-26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Rice M et al (2014) SMYD2 structure and function: a multispecificity protein lysine methyltransferase. J Cytol Mol Biol 1:7

    Google Scholar 

  18. Du SJ, Tan X, Zhang J (2014) SMYD Proteins: Key Regulators in Skeletal and Cardiac Muscle Development and Function. Anatomical Record (Hoboken, N. J.: 2007) 297:1650–1662. https://doi.org/10.1002/ar.22972

    Article  CAS  PubMed  Google Scholar 

  19. Spellmon N, Holcomb J, Trescott L, Sirinupong N, Yang Z (2015) Structure and Function of SET and MYND Domain-Containing Proteins. Int J Mol Sci 16

  20. Tracy C et al (2018) The Smyd family of methyltransferases: role in cardiac and skeletal muscle physiology and pathology. Curr Opin Physiol 1:140–152. https://doi.org/10.1016/j.cophys.2017.10.001

    Article  PubMed  Google Scholar 

  21. Abu-Farha M et al (2008) The tale of two domains: proteomics and genomics analysis of SMYD2, a new histone methyltransferase. Molecular & cellular proteomics : MCP 7:560–572. https://doi.org/10.1074/mcp.M700271-MCP200

    Article  CAS  PubMed  Google Scholar 

  22. Boehm D et al (2017) SMYD2-Mediated Histone Methylation Contributes to HIV-1 Latency. Cell Host Microbe 21:569-579 e566. https://doi.org/10.1016/j.chom.2017.04.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Huang J et al (2006) Repression of p53 activity by SMYD2-mediated methylation. Nature 444:629–632. https://doi.org/10.1038/nature05287

    Article  CAS  PubMed  Google Scholar 

  24. Abu-Farha M et al (2011) Proteomic analyses of the SMYD family interactomes identify HSP90 as a novel target for SMYD2. J Mol Cell Biol 3:301–308. https://doi.org/10.1093/jmcb/mjr025

    Article  CAS  PubMed  Google Scholar 

  25. Cho HS et al (2012) RB1 methylation by SMYD2 enhances cell cycle progression through an increase of RB1 phosphorylation. Neoplasia (New York, N.Y.) 14:476–486

    Article  CAS  PubMed  Google Scholar 

  26. Zhang X et al (2013) Regulation of estrogen receptor alpha by histone methyltransferase SMYD2-mediated protein methylation. Proc Natl Acad Sci USA 110:17284–17289. https://doi.org/10.1073/pnas.1307959110

    Article  PubMed  PubMed Central  Google Scholar 

  27. Piao L et al (2014) The histone methyltransferase SMYD2 methylates PARP1 and promotes poly(ADP-ribosyl)ation activity in cancer cells. Neoplasia 16:257–264. https://doi.org/10.1016/j.neo.2014.03.002. (264.e252)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zeng Y et al (2019) Regulation of EZH2 by SMYD2-Mediated Lysine Methylation Is Implicated in Tumorigenesis. Cell Rep 29:1482-1498 e1484. https://doi.org/10.1016/j.celrep.2019.10.004

    Article  CAS  PubMed  Google Scholar 

  29. Li LX et al (2017) Lysine methyltransferase SMYD2 promotes cyst growth in autosomal dominant polycystic kidney disease. J Clin Investig 127:2751–2764. https://doi.org/10.1172/JCI90921

    Article  PubMed  PubMed Central  Google Scholar 

  30. Li LX et al (2018) Lysine methyltransferase SMYD2 promotes triple negative breast cancer progression. Cell Death Dis 9:326. https://doi.org/10.1038/s41419-018-0347-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yi X, Jiang XJ, Fang ZM (2019) Histone methyltransferase SMYD2: ubiquitous regulator of disease. Clin Epigenetics 11:112. https://doi.org/10.1186/s13148-019-0711-4

    Article  PubMed  PubMed Central  Google Scholar 

  32. Diehl F et al (2010) Cardiac deletion of SMYD2 is dispensable for mouse heart development. PLoS ONE 5:e9748. https://doi.org/10.1371/journal.pone.0009748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Voelkel T et al (2013) Lysine methyltransferase SMYD2 regulates Hsp90-mediated protection of the sarcomeric titin springs and cardiac function. Biochem Biophys Acta 1833:812–822. https://doi.org/10.1016/j.bbamcr.2012.09.012

    Article  CAS  PubMed  Google Scholar 

  34. Xu G et al (2015) The histone methyltransferase SMYD2 is a negative regulator of macrophage activation by suppressing interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) production. J Biol Chem 290:5414–5423. https://doi.org/10.1074/jbc.M114.610345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Jones GT et al (2017) Meta-analysis of genome-wide association studies for abdominal aortic aneurysm identifies four new disease-specific risk loci. Circ Res 120:341–353. https://doi.org/10.1161/CIRCRESAHA.116.308765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Toghill BJ, Saratzis A, Freeman PJ, Sylvius N, Bown MJ (2018) SMYD2 promoter DNA methylation is associated with abdominal aortic aneurysm (AAA) and SMYD2 expression in vascular smooth muscle cells. Clin Epigenetics 10:29. https://doi.org/10.1186/s13148-018-0460-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Skarnes WC et al (2011) A conditional knockout resource for the genome-wide study of mouse gene function. Nature 474:337–342. https://doi.org/10.1038/nature10163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Holtwick R et al (2002) Smooth muscle-selective deletion of guanylyl cyclase-A prevents the acute but not chronic effects of ANP on blood pressure. Proc Natl Acad Sci USA 99:7142–7147. https://doi.org/10.1073/pnas.102650499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hu G et al (2010) Modulation of myocardin function by the ubiquitin E3 ligase UBR5. J Biol Chem 285:11800–11809. https://doi.org/10.1074/jbc.M109.079384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wang X et al (2012) The induction of yes-associated protein expression after arterial injury is crucial for smooth muscle phenotypic modulation and neointima formation. Arterioscler Thromb Vasc Biol 32:2662–2669. https://doi.org/10.1161/atvbaha.112.254730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Osman I et al (2019) TEAD1 (TEA Domain Transcription Factor 1) Promotes Smooth Muscle Cell Proliferation Through Upregulating SLC1A5 (Solute Carrier Family 1 Member 5)-Mediated Glutamine Uptake. Circ Res 124:1309–1322. https://doi.org/10.1161/CIRCRESAHA.118.314187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Xu F et al (2015) MicroRNA-15b/16 attenuates vascular neointima formation by promoting the contractile phenotype of vascular smooth muscle through targeting YAP. Arterioscler Thromb Vasc Biol 35:2145–2152. https://doi.org/10.1161/atvbaha.115.305748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wen T et al (2019) Transcription factor TEAD1 is essential for vascular development by promoting vascular smooth muscle differentiation. Cell Death Differ 26:2790–2806. https://doi.org/10.1038/s41418-019-0335-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rothman A et al (1992) Development and characterization of a cloned rat pulmonary arterial smooth muscle cell line that maintains differentiated properties through multiple subcultures. Circulation 86:1977–1986

    Article  CAS  PubMed  Google Scholar 

  45. Eggert E et al (2016) Discovery and characterization of a highly potent and selective aminopyrazoline-based in vivo probe (BAY-598) for the protein lysine methyltransferase SMYD2. J Med Chem 59:4578–4600. https://doi.org/10.1021/acs.jmedchem.5b01890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Shang L, Wei M (2019) Inhibition of SMYD2 sensitized cisplatin to resistant cells in NSCLC through activating p53 pathway. Front Oncol 9:306. https://doi.org/10.3389/fonc.2019.00306

    Article  PubMed  PubMed Central  Google Scholar 

  47. Ran FA et al (2013) Genome engineering using the CRISPR-Cas9 system. Nat Protoc 8:2281–2308. https://doi.org/10.1038/nprot.2013.143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zhou Y et al (2019) LncRNA CRNDE regulates the proliferation and migration of vascular smooth muscle cells. J Cell Physiol 234:16205–16214. https://doi.org/10.1002/jcp.28284

    Article  CAS  PubMed  Google Scholar 

  49. Farooq SM et al (2018) Disruption of GPR35 exacerbates dextran sulfate sodium-induced colitis in mice. Dig Dis Sci 63:2910–2922. https://doi.org/10.1007/s10620-018-5216-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Li C et al (2007) Spatiotemporal coupling of cAMP transporter to CFTR chloride channel function in the gut epithelia. Cell 131:940–951. https://doi.org/10.1016/j.cell.2007.09.037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Hou Y et al (2015) A critical role of CXCR2 PDZ-mediated interactions in endothelial progenitor cell homing and angiogenesis. Stem cell research 14:133–143. https://doi.org/10.1016/j.scr.2014.12.001

    Article  CAS  PubMed  Google Scholar 

  52. Wu Y et al (2012) A chemokine receptor CXCR2 macromolecular complex regulates neutrophil functions in inflammatory diseases. J Biol Chem 287:5744–5755. https://doi.org/10.1074/jbc.M111.315762

    Article  CAS  PubMed  Google Scholar 

  53. Zhou J, Blue EK, Hu G, Herring BP (2008) Thymine DNA glycosylase represses myocardin-induced smooth muscle cell differentiation by competing with serum response factor for myocardin binding. J Biol Chem 283:35383–35392. https://doi.org/10.1074/jbc.M805489200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Salmon M, Gomez D, Greene E, Shankman L, Owens GK (2012) Cooperative binding of KLF4, pELK-1, and HDAC2 to a G/C repressor element in the SM22alpha promoter mediates transcriptional silencing during SMC phenotypic switching in vivo. Circ Res 111:685–696. https://doi.org/10.1161/circresaha.112.269811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Nagao M et al (2020) Coronary disease-associated gene TCF21 Inhibits smooth muscle cell differentiation by blocking the myocardin-serum response factor pathway. Circ Res 126:517–529. https://doi.org/10.1161/CIRCRESAHA.119.315968

    Article  CAS  PubMed  Google Scholar 

  56. Liu J et al (2021) TEAD1 protects against necroptosis in postmitotic cardiomyocytes through regulation of nuclear DNA-encoded mitochondrial genes. Cell Death Differ. https://doi.org/10.1038/s41418-020-00732-5

    Article  PubMed  PubMed Central  Google Scholar 

  57. Mack CP, Owens GK (1999) Regulation of smooth muscle alpha-actin expression in vivo is dependent on CArG elements within the 5’ and first intron promoter regions. Circ Res 84:852–861

    Article  CAS  PubMed  Google Scholar 

  58. Owens GK, Kumar MS, Wamhoff BR (2004) Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 84:767–801

    Article  CAS  PubMed  Google Scholar 

  59. Kumar A, Lindner V (1997) Remodeling with neointima formation in the mouse carotid artery after cessation of blood flow. Arterioscler Thromb Vasc Biol 17:2238–2244. https://doi.org/10.1161/01.atv.17.10.2238

    Article  CAS  PubMed  Google Scholar 

  60. Yang F et al (2018) miR-22 is a novel mediator of vascular smooth muscle cell phenotypic modulation and neointima formation. Circulation 137:1824–1841. https://doi.org/10.1161/circulationaha.117.027799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Holycross BJ, Blank RS, Thompson MM, Peach MJ, Owens GK (1992) Platelet-derived growth factor-BB-induced suppression of smooth muscle cell differentiation. Circ Res 71:1525–1532

    Article  CAS  PubMed  Google Scholar 

  62. Jawien A, Bowen-Pope DF, Lindner V, Schwartz SM, Clowes AW (1992) Platelet-derived growth factor promotes smooth muscle migration and intimal thickening in a rat model of balloon angioplasty. J Clin Investig 89:507–511. https://doi.org/10.1172/JCI115613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Cao D et al (2005) Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin. Mol Cell Biol 25:364–376. https://doi.org/10.1128/mcb.25.1.364-376.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Spellmon N, Holcomb J, Trescott L, Sirinupong N, Yang Z (2015) Structure and function of SET and MYND domain-containing proteins. Int J Mol Sci 16:1406–1428. https://doi.org/10.3390/ijms16011406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Talasila A et al (2013) Myocardin regulates vascular response to injury through miR-24/-29a and platelet-derived growth factor receptor-beta. Arterioscler Thromb Vasc Biol 33:2355–2365. https://doi.org/10.1161/atvbaha.112.301000

    Article  CAS  PubMed  Google Scholar 

  66. Ackers-Johnson M et al (2015) Myocardin regulates vascular smooth muscle cell inflammatory activation and disease. Arterioscler Thromb Vasc Biol 35:817–828. https://doi.org/10.1161/atvbaha.114.305218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Ueyama T, Kasahara H, Ishiwata T, Nie Q, Izumo S (2003) Myocardin expression is regulated by Nkx2.5, and its function is required for cardiomyogenesis. Mol Cell Biol 23:9222–9232. https://doi.org/10.1128/mcb.23.24.9222-9232.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Ruthenburg AJ, Allis CD, Wysocka J (2007) Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark. Mol Cell 25:15–30. https://doi.org/10.1016/j.molcel.2006.12.014

    Article  CAS  PubMed  Google Scholar 

  69. Wang Z et al (2009) Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell 138:1019–1031. https://doi.org/10.1016/j.cell.2009.06.049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. McDonald OG, Wamhoff BR, Hoofnagle MH, Owens GK (2006) Control of SRF binding to CArG box chromatin regulates smooth muscle gene expression in vivo. J Clin Investig 116:36–48. https://doi.org/10.1172/jci26505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hu M, Hiroyasu S, Granville DJ, Kassiri Z (2022) Implications of Sm22alpha-Cre expression in keratinocytes and unanticipated inflammatory skin lesion in a model of atherosclerosis. Am J Physiol Heart Circ Physiol 323:H528–H534. https://doi.org/10.1152/ajpheart.00325.2022

    Article  CAS  PubMed  Google Scholar 

  72. Chakraborty R et al (2019) Promoters to study vascular smooth muscle. Arterioscler Thromb Vasc Biol 39:603–612. https://doi.org/10.1161/ATVBAHA.119.312449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Warthi G et al (2022) Generation and comparative analysis of an Itga8-CreER (T2) mouse with preferential activity in vascular smooth muscle cells. Nat Cardiovasc Res 1:1084–1100. https://doi.org/10.1038/s44161-022-00162-1

    Article  PubMed  PubMed Central  Google Scholar 

  74. Yang D et al (2021) H3K4 methyltransferase Smyd3 mediates vascular smooth muscle cell proliferation, migration, and neointima formation. Arterioscler Thromb Vasc Biol 41:1901–1914. https://doi.org/10.1161/ATVBAHA.121.314689

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Dr. Chengliu Jin and Zoe Liu (Transgenic Core at GSU) for generous help with generating the SMYD2 KO mice.

Funding

This work was supported by startup fund from Georgia State University (to C Li) and by grants from National Natural Science Foundation of China (82000448 to Y Zhou) and from National Institutes of Health (HL128647 to C Li, HL149995 to J Zhou, and HL140954 to P Song and M-H Zou). C Li is a recipient of Transformational Project Award (20TPA35410012) from American Heart Association. S. Sharma is a recipient of Pre-doctoral Fellowship (917128) from American Heart Association. J Zhou is a recipient of Established Investigator Award (17EIA33460468) and Transformational Project Award (19TPA34910181) from American Heart Association. M-H Zou is a Georgia Research Alliance Eminent Scholar in Molecular Medicine.

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  1. Yuning Hou

    Present address: Cancer Animal Models Shared Resource, Winship Cancer Institute, Emory University, Atlanta, GA, USA

Authors and Affiliations

  1. Center for Molecular and Translational Medicine, Institute for Biomedical Sciences, Georgia State University, 157 Decatur St SE, Atlanta, GA, 30303, USA

    Yu Zhou, Shaligram Sharma, Xiaonan Sun, Xiaoqing Guan, Yuning Hou, Ming-Hui Zou, Ping Song & Chunying Li

  2. Division of Vascular Surgery, National-Local Joint Engineering Laboratory of Vascular Disease Treatment, Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangdong Engineering Laboratory of Diagnosis and Treatment of Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, No 58, Zhongshan 2nd Street, Yuexiu District, Guangzhou, 510080, Guangdong, China

    Yu Zhou, Shenming Wang & Zuojun Hu

  3. Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI, USA

    Zhe Yang

  4. Department of Biology, Center for Obesity Reversal, Georgia State University, Atlanta, GA, USA

    Hang Shi

  5. Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA, USA

    Jiliang Zhou

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Contributions

YZ designed and performed most of the experiments and analyzed data. SS and XS performed some data collection. CL and ZH conceived, designed, and supervised the study. YZ and CL wrote and revised the manuscript. JZ and PS provided reagents and revised the manuscript. XG, YH, ZY, HS, M-HZ, PS, JZ, and SW contributed to discussion and interpretation of the data and review of the manuscript. All authors reviewed and approved the final version of the manuscript.

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Correspondence to Yu Zhou, Zuojun Hu or Chunying Li.

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Zhou, Y., Sharma, S., Sun, X. et al. SMYD2 regulates vascular smooth muscle cell phenotypic switching and intimal hyperplasia via interaction with myocardin. Cell. Mol. Life Sci. 80, 264 (2023). https://doi.org/10.1007/s00018-023-04883-9

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  • DOI: https://doi.org/10.1007/s00018-023-04883-9

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