TY - JOUR
T1 - IL-17A promotes vascular calcification in an ex vivo murine aorta culture
AU - Hiramatsu-Asano, Sumie
AU - Mukai, Tomoyuki
AU - Akagi, Takahiko
AU - Uchida, Haruhito A.
AU - Fujita, Shunichi
AU - Nakano, Kazuhisa
AU - Morita, Yoshitaka
N1 - Funding Information:
This work was supported by JSPS Grant-in-Aid for Scientific Research [grant numbers 20K17442 to S.H.A., 20K08875 to S.F., and 21K08484 to T.M.]; Health Labour Sciences Research Grant [grant number 20FC1047 to T.M.]; the Japan Rheumatism Foundation [research grant to S.H.A.]; the Takeda Science Foundation [research grant to S.H.A.]; the Japan Arteriosclerosis Prevention Foundation [research grant to S.H.A.]; Kawasaki Medical School [research project grant numbers R02B-065 and R03B-090 to S.H.A.]; Wesco Scientific Promotion Foundation [research grant to S.H.A.]; and UCB Japan [research grant to T.M.].
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/5/14
Y1 - 2022/5/14
N2 - Background: Vascular calcification is characterized by mineral deposition in the vasculature, which is triggered by chronic systemic inflammation, including psoriasis. Psoriasis is an IL-17A-mediated inflammatory skin disease that is associated with exacerbated vascular calcification and high cardiovascular mortality. Although previous studies have shown that IL-17A induces vascular dysfunction in murine psoriasis models, it has not been clarified whether IL-17A induces vascular calcification. In this study, we investigated the potential vascular calcification-inducing effect of IL-17A in an ex vivo culture system. Methods: Thoracic and abdominal aortas from mice were cultured in a medium supplemented with inorganic phosphate and were treated with inflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-17A). Vascular calcification was determined using micro-computed tomography (CT) and histological analyses. Results: IL-1β, TNF-α, and IL-6 did not significantly promote vascular calcification, whereas IL-17A significantly accelerated vascular calcification of the aorta, as indicated by the increased mineralized volume based on micro-CT analysis. Micro-CT and histological analyses also revealed that the promoting effect of IL-17A on vascular calcification was concentration dependent. Conclusions: IL-17A significantly promoted vascular calcification in ex vivo cultured aortas, which suggests that this mechanism is involved in the increased risk of cardiovascular events in IL-17A-mediated inflammatory diseases.
AB - Background: Vascular calcification is characterized by mineral deposition in the vasculature, which is triggered by chronic systemic inflammation, including psoriasis. Psoriasis is an IL-17A-mediated inflammatory skin disease that is associated with exacerbated vascular calcification and high cardiovascular mortality. Although previous studies have shown that IL-17A induces vascular dysfunction in murine psoriasis models, it has not been clarified whether IL-17A induces vascular calcification. In this study, we investigated the potential vascular calcification-inducing effect of IL-17A in an ex vivo culture system. Methods: Thoracic and abdominal aortas from mice were cultured in a medium supplemented with inorganic phosphate and were treated with inflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-17A). Vascular calcification was determined using micro-computed tomography (CT) and histological analyses. Results: IL-1β, TNF-α, and IL-6 did not significantly promote vascular calcification, whereas IL-17A significantly accelerated vascular calcification of the aorta, as indicated by the increased mineralized volume based on micro-CT analysis. Micro-CT and histological analyses also revealed that the promoting effect of IL-17A on vascular calcification was concentration dependent. Conclusions: IL-17A significantly promoted vascular calcification in ex vivo cultured aortas, which suggests that this mechanism is involved in the increased risk of cardiovascular events in IL-17A-mediated inflammatory diseases.
KW - Aorta
KW - Chronic inflammation
KW - Ex vivo culture
KW - IL-17A
KW - Vascular calcification
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U2 - 10.1016/j.bbrc.2022.03.051
DO - 10.1016/j.bbrc.2022.03.051
M3 - Article
C2 - 35303683
AN - SCOPUS:85126537380
SN - 0006-291X
VL - 604
SP - 83
EP - 87
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
ER -