2. Academic Validation
  3. Nattokinase attenuates endothelial inflammation through the activation of SRF and THBS1

Nattokinase attenuates endothelial inflammation through the activation of SRF and THBS1

  • Int J Biol Macromol. 2024 May;268(Pt 2):131779. doi: 10.1016/j.ijbiomac.2024.131779.
Hui-Wen Chiu 1,  Chu-Lin Chou 2,  Kung-Ta Lee 3,  Chun-Che Shih 4,  Tzu-Hsuan Huang 5,  Li-Chin Sung 6
Affiliations

Affiliations

  • 1 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan.
  • 2 TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan; Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Nephrology, Department of Internal Medicine, Hsin Kuo Min Hospital, Taipei Medical University, Taoyuan City, Taiwan; Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
  • 3 Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan.
  • 4 Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan; Division of Cardiovascular Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 5 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 6 TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan; Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Department of General Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. Electronic address: 10204@s.tmu.edu.tw.
PMID: 38679250 DOI: 10.1016/j.ijbiomac.2024.131779
Abstract

Natto contains a potent fibrinolytic Enzyme called nattokinase (NK), which has thrombolytic, antihypertensive, antiatherosclerotic and lipid-lowering effects. Although NK has been recognized for its beneficial effect on humans with atherosclerotic Cardiovascular Disease (ASCVD), the underlying mechanisms involved in vascular inflammation-atherosclerosis development remain largely unknown. The current study aimed to explore the effects of NK on gene regulation, Autophagy, Necroptosis and inflammasome in vascular inflammation. The transcriptional profiles of NK in endothelial cells (ECs) by RNA sequencing (RNA-seq) revealed that NK affected THBS1, SRF and SREBF1 mRNA expression. In Q-PCR analysis, SRF and THBS1 were upregulated but SREBF1 was unaffected in ECs treated with NK. NK treatment induced Autophagy and inhibited NLRP3 inflammasome and Necroptosis in ECs. Furthermore, the inhibition of SRF or THBS1 by siRNA suppressed Autophagy and enhanced the NLRP3 inflammasome and Necroptosis. In a mouse model, NK reduced vascular inflammation by activating Autophagy and inhibiting NLRP3 inflammasome and Necroptosis. Our findings provide the first evidence that NK upregulates SRF and THBS1 genes, subsequently increasing Autophagy and decreasing Necroptosis and NLRP3 inflammasome formation to reduce vascular inflammation. Therefore, NK could serve as nutraceuticals or adjuvant therapies to reduce vascular inflammation and possible atherosclerosis progression.

Keywords

Autophagy; NLRP3 inflammasome; Nattokinase; Necroptosis; Vascular inflammation.

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