IL-5 overexpression attenuates aortic dissection by reducing inflammation and smooth muscle cell apoptosis

Life Sci. 2020 Jan 15:241:117144. doi: 10.1016/j.lfs.2019.117144. Epub 2019 Dec 9.

Abstract

Background: As an inflammation-related cytokine, interleukin (IL)-5 has been reported to be involved in the development of cardiovascular diseases, such as chronic heart failure and atherosclerosis. However, the role of IL-5 in acute aortic dissection (AAD) has barely been explored.

Methods: Aortic tissue samples from normal donors and patients with AAD were collected, and the expression and localization of IL-5 in aortic tissue were analyzed. In addition, a mouse AAD model was established by administering angiotensin II (Ang II) to β-aminopropionitrile (BAPN)-treated mice. Morphological examinations and histopathologic analyses were performed to evaluate the effects of IL-5 overexpression on the occurrence of AAD.

Results: IL-5 expression was significantly decreased in aorta samples from AAD patients compared to those from donors, and macrophages were the main source of IL-5. In addition, IL-5 expression was decreased in plasma and aortic tissue samples from AAD mice. IL-5 overexpression markedly attenuated the occurrence of AAD in mice and produced corresponding decreases in the inflammatory response and cell apoptosis. In cocultures of macrophages and smooth muscle cells (SMCs), IL-5 overexpression in the macrophages significantly reduced Ang II-induced SMC apoptosis.

Conclusion: IL-5 overexpression suppresses the development of AAD by reducing inflammation and SMC apoptosis. These results suggest that IL-5 is a potential therapeutic target in AAD.

Keywords: Acute aortic dissection; Interleukin; Macrophages; Smooth muscle cells.

MeSH terms

  • Aminopropionitrile / toxicity
  • Angiotensin II / toxicity
  • Animals
  • Aorta / metabolism
  • Aorta / pathology
  • Aortic Dissection / chemically induced
  • Aortic Dissection / complications
  • Aortic Dissection / metabolism
  • Aortic Dissection / prevention & control*
  • Apoptosis*
  • Case-Control Studies
  • Disease Models, Animal*
  • Female
  • Humans
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Interleukin-5 / genetics
  • Interleukin-5 / metabolism*
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology*
  • Prognosis

Substances

  • Interleukin-5
  • Angiotensin II
  • Aminopropionitrile