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CCL7 contributes to angiotensin II-induced abdominal aortic aneurysm by promoting macrophage infiltration and pro-inflammatory phenotype.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2021 Aug; Vol. 25 (15), pp. 7280-7293. Date of Electronic Publication: 2021 Jun 29. - Publication Year :
- 2021
-
Abstract
- Chemokine C-C motif ligand 7 (CCL7), a member of CC chemokine subfamily, plays pivotal roles in numerous inflammatory diseases. Hyper-activation of inflammation is an important characteristic of abdominal aortic aneurysm (AAA). Therefore, in the present study, we aimed to determine the effect of CCL7 on AAA formation. CCL7 abundance in aortic tissue and macrophage infiltration were both increased in angiotensin II (Ang II)-induced AAA mice. Ex vivo, CCL7 promoted macrophage polarization towards M1 phenotype. This effect was reversed by the blockage of CCR1, a receptor of CCL7. CCL7 up-regulated JAK2/STAT1 protein level in macrophage, and CCL7-induced M1 activation was suppressed by JAK2/STAT1 pathway inhibition. To verify the effect of CCL7 on AAA in vivo, either CCL7-neutralizing antibody (CCL7-nAb) or vehicles were intraperitoneally injected 24 hours prior to Ang II infusion and subsequently every three days for 4 weeks. CCL7-nAb administration significantly attenuated Ang II-induced luminal and external dilation as well as pathological remodelling. Immunostaining showed that CCL7-nAb administration significantly decreased aneurysmal macrophage infiltration. In conclusion, CCL7 contributed to Ang II-induced AAA by promoting M1 phenotype of macrophage through CCR1/JAK2/STAT1 signalling pathway.<br /> (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
- Subjects :
- Angiotensin II toxicity
Animals
Aortic Aneurysm, Abdominal etiology
Aortic Aneurysm, Abdominal pathology
Cell Differentiation
Cells, Cultured
Chemokine CCL7 antagonists & inhibitors
Human Umbilical Vein Endothelial Cells metabolism
Humans
Janus Kinase 2 metabolism
Macrophages physiology
Male
Mice
Mice, Inbred C57BL
Phenotype
Receptors, CCR1 metabolism
STAT1 Transcription Factor metabolism
Vascular Remodeling
Aortic Aneurysm, Abdominal metabolism
Cell Movement
Chemokine CCL7 metabolism
Macrophages metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 25
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 34189838
- Full Text :
- https://doi.org/10.1111/jcmm.16757