Reducing SULT2B1 promotes the interaction of LncRNAgga3-204 with SMAD4 to inhibit the macrophage inflammatory response and delay atherosclerosis progression.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 101280339 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1810 (Electronic) Linking ISSN: 18781810 NLM ISO Abbreviation: Transl Res Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York, N.Y. : Elsevier, [2006]-
    • Subject Terms:
      Atherosclerosis*/metabolism ; Atherosclerosis*/genetics ; Atherosclerosis*/pathology ; Sulfotransferases*/genetics ; Sulfotransferases*/metabolism ; Macrophages*/metabolism ; Inflammation*/metabolism ; Inflammation*/pathology ; Smad4 Protein*/metabolism ; Smad4 Protein*/genetics ; Disease Progression*; Animals ; Mice ; Humans ; Male ; Mice, Inbred C57BL ; Female
    • Abstract:
      Inflammation is a crucial pathophysiological mechanism in atherosclerosis (AS). This study aims to investigate the impact of sulfotransferase family 2b member 1 (SULT2B1) on the inflammatory response of macrophages and the progression of AS. Here, we reported that SULT2B1 expression increased with the progression of AS. In AS model mice, knockdown of Sult2b1 led to remission of AS and reduced inflammation levels. Further exploration of the downstream molecular mechanisms of SULT2B1 revealed that suppressing Sult2b1 in macrophages resulted in decreased levels of 25HC3S in the nucleus, elevated expression of Lxr, and increased the transcription of Lncgga3-204. In vivo, knockdown of Lncgga3-204 aggravated the inflammatory response and AS progression, while the simultaneous knockdown of both Sult2b1 and Lncgga3-204 exacerbated AS and the inflammatory response compared with knockdown of Sult2b1 alone. Increased binding of Lncgga3-204 to SMAD4 in response to oxidized-low density lipoprotein (ox-LDL) stimulation facilitated SMAD4 entry into the nucleus and regulated Smad7 transcription, which elevated SMAD7 expression, suppressed NF-κB entry into the nucleus, and ultimately attenuated the macrophage inflammatory response. Finally, we identified the presence of a single nucleotide polymorphism (SNP), rs2665580, in the SULT2B1 promoter region in monocytes from coronary artery disease (CAD) patients. The predominant GG/AG/AA genotypes were observed in the Asian population. Elevated SULT2B1 expression in monocytes with GG corresponded to elevated inflammatory factor levels and more unstable coronary plaques. To summarize, our study demonstrated that the critical role of SULT2B1/Lncgga3-204/SMAD4/NF-κB in AS progression. SULT2B1 serves as a novel biomarker indicating inflammatory status, thereby offering insights into potential therapeutic strategies for AS.
      Competing Interests: Conflict of interests All authors have read the journal's policy on disclosure of potential conflicts of interest and have none to declare.
      (Copyright © 2024 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Atherosclerosis; Inflammation; LncRNA; Macrophage; Sulfotransferase family 2b member 1
    • Accession Number:
      EC 2.8.2.- (Sulfotransferases)
      0 (Smad4 Protein)
      EC 2.8.2.- (SULT2B1b protein, mouse)
      EC 2.8.2.2 (SULT2B1 protein, human)
    • Publication Date:
      Date Created: 20240129 Date Completed: 20240508 Latest Revision: 20240517
    • Publication Date:
      20240517
    • Accession Number:
      10.1016/j.trsl.2024.01.004
    • Accession Number:
      38286358