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.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / toxicity
  • Animals
  • Anti-Inflammatory Agents / metabolism*
  • Aorta, Abdominal / drug effects
  • Aorta, Abdominal / immunology
  • Aorta, Abdominal / pathology
  • Aortic Aneurysm, Abdominal / chemically induced
  • Aortic Aneurysm, Abdominal / immunology*
  • Aortic Aneurysm, Abdominal / pathology
  • Calcium Chloride / toxicity
  • Chemokine CCL3 / genetics
  • Chemokine CCL3 / metabolism*
  • Disease Models, Animal
  • Humans
  • Inflammation Mediators / metabolism
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Knockout
  • Receptors, CCR1 / genetics
  • Receptors, CCR1 / metabolism
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Specific Pathogen-Free Organisms


  • Anti-Inflammatory Agents
  • CCR5 protein, mouse
  • Ccl3 protein, mouse
  • Ccr1 protein, mouse
  • Chemokine CCL3
  • Inflammation Mediators
  • Receptors, CCR1
  • Receptors, CCR5
  • Angiotensin II
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse
  • Calcium Chloride