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.
Abbreviations:
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)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: August 21, 2020
Accepted:
August 17,
2020
Received in revised form:
July 27,
2020
Received:
April 13,
2020
Identification
Copyright
© 2020 Elsevier Inc. All rights reserved.
