IL-17A promotes vascular calcification in an ex vivo murine aorta culture

Biochem Biophys Res Commun. 2022 May 14:604:83-87. doi: 10.1016/j.bbrc.2022.03.051. Epub 2022 Mar 10.

Abstract

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.

Keywords: Aorta; Chronic inflammation; Ex vivo culture; IL-17A; Vascular calcification.

MeSH terms

  • Animals
  • Aorta, Abdominal
  • Inflammation / complications
  • Interleukin-17* / pharmacology
  • Interleukin-17* / physiology
  • Interleukin-6 / pharmacology
  • Mice
  • Psoriasis* / complications
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Calcification* / etiology
  • Vascular Calcification* / metabolism
  • X-Ray Microtomography

Substances

  • Il17a protein, mouse
  • Interleukin-17
  • Interleukin-6
  • Tumor Necrosis Factor-alpha