Substance P blocks β-aminopropionitrile-induced aortic injury through modulation of M2 monocyte-skewed monocytopoiesis

  • Jiyuan Piao
    Department of Genetic Engineering, College of Life Science and Graduate School of Biotechnology, Kyung Hee University, Yong In, South Korea
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  • Jeong Seop Park
    Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, South Korea
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  • Dae Yeon Hwang
    East-West Medical Research Institute, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, South Korea
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  • Hyun Sook Hong
    Reprint requests: Hyun Sook Hong, Ph.D.; Phone: +82-2-958-1828; or Youngsook Son, Ph.D.; Phone: +82-31-201-3826.
    Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, South Korea

    East-West Medical Research Institute, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, South Korea
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  • Youngsook Son
    Reprint requests: Hyun Sook Hong, Ph.D.; Phone: +82-2-958-1828; or Youngsook Son, Ph.D.; Phone: +82-31-201-3826.
    Department of Genetic Engineering, College of Life Science and Graduate School of Biotechnology, Kyung Hee University, Yong In, South Korea
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Published:August 21, 2020DOI:
      Aortic injuries, including aortic aneurysms and dissections, are fatal vascular diseases with distinct histopathological features in the aortic tissue such as inflammation-induced endothelial dysfunction, infiltration of immune cells, and breakdown of the extracellular matrix. Few treatments are available for treating aortic aneurysms and dissections; thus, basic and clinical studies worldwide have been attempted to inhibit disease progression.
      Substance P (SP) exerts anti-inflammatory effects and promotes restoration of the damaged endothelium, leading to vasculature protection and facilitation of tissue repair. This study was conducted to explore the protective effects of systemically injected SP on thoracic aortic injury (TAI). A TAI animal model was induced by orally administering β-aminopropionitrile to rats for 6 weeks. β-aminopropionitrile blocked crosslinking ECM in aorta to cause structural alteration with inflammation within 1 week and then, induced aortic dissection within 4 weeks of initiating treatment, leading to mortality within 6 weeks. Treatment of TAI rats with SP-induced anti-inflammatory responses systemically and locally, possibly by enriching anti-inflammatory M2 monocytes in the spleen and peripheral blood at early phase of aortic injury due to β-aminopropionitrile. SP-induced immune suppression finally prevented the development of aortic dissection by limiting inflammation-mediated aortic destruction.
      Taken together, these results suggest that SP treatment can block aortic injury by controlling the immune-cell profile and suppressing proinflammatory responses during the initial stage of vascular disease progression.


      Arg-1 (arginase-1), α-SMA (alpha-smooth muscle actin), BAPN (β-aminopropionitrile), BM (bone marrow), CFU (colony forming unit), CRP (C-reactive protein), IL-10 (interleukin-10), iNOS (inducible nitric oxide synthase), LOX (lysyl oxidase), MCP-1 (monocyte chemoattractant protein-1), MMP (matrix metalloproteinase), NK-1R (neurokinin-1 receptor), OPN (osteopontin), SMC (smooth muscle cell), SP (substance p), TNF-α (tumor necrosis factor-alpha), VCAM-1 (vascular cell adhesion protein-1)
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