1. Academic Validation
  2. Prevention of CaCl2-induced aortic inflammation and subsequent aneurysm formation by the CCL3-CCR5 axis

Prevention of CaCl2-induced aortic inflammation and subsequent aneurysm formation by the CCL3-CCR5 axis

  • Nat Commun. 2020 Nov 25;11(1):5994. doi: 10.1038/s41467-020-19763-0.
Yuko Ishida 1 Yumi Kuninaka 1 Mizuho Nosaka 1 Akihiko Kimura 1 Akira Taruya 2 Machi Furuta 3 Naofumi Mukaida 4 Toshikazu Kondo 5
Affiliations

Affiliations

  • 1 Department of Forensic Medicine, Wakayama Medical University, Wakayama, Japan.
  • 2 Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan.
  • 3 Department of Clinical Laboratory Medicine, Wakayama Medical University, Wakayama, Japan.
  • 4 Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
  • 5 Department of Forensic Medicine, Wakayama Medical University, Wakayama, Japan. kondot@wakayama-med.ac.jp.
Abstract

Inflammatory mediators such as cytokines and chemokines are crucially involved in the development of abdominal aortic aneurysm (AAA). Here we report that CaCl2 application into abdominal aorta induces AAA with intra-aortic infiltration of macrophages as well as enhanced expression of chemokine (C-C motif) ligand 3 (CCL3) and MMP-9. Moreover, infiltrating macrophages express C-C Chemokine Receptor 5 (CCR5, a specific receptor for CCL3) and MMP-9. Both Ccl3-/- mice and CCR5-/- but not CCR1-/- mice exhibit exaggerated CaCl2-inducced AAA with augmented macrophage infiltration and MMP-9 expression. Similar observations are also obtained on an angiotensin II-induced AAA model. Immunoneutralization of CCL3 mimics the phenotypes observed in CaCl2-treated Ccl3-/- mice. On the contrary, CCL3 treatment attenuates CaCl2-induced AAA in both wild-type and Ccl3-/- mice. Consistently, we find that the CCL3-CCR5 axis suppresses PMA-induced enhancement of MMP-9 expression in macrophages. Thus, CCL3 can be effective to prevent the development of CaCl2-induced AAA by suppressing MMP-9 expression.

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