Deletion of NF-κB/RelA in angiotensin II-sensitive mesenchymal cells blocks aortic vascular inflammation and abdominal aortic aneurysm formation

Talha Ijaz, Hong Sun, Irina V. Pinchuk, Dianna M. Milewicz, Ronald G. Tilton, Allan R. Brasier

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Objective - Infusion of angiotensin II (Ang II) induces extracellular matrix remodeling and inflammation resulting in abdominal aortic aneurysms (AAAs) in normolipidemic mice. Although Ang II activates mesenchymal cells in the media and adventitia to become fibrogenic, the sentinel role of this mesenchymal population in modulating the inflammatory response and aneurysms is not known. We test the hypothesis that these fibrogenic mesenchymal cells play a critical role in Ang II-induced aortic wall vascular inflammation and AAA formation. Approach and Results - Ang II infusion increased phospho-Ser536-RelA and interleukin (IL)-6 immunostaining in the abdominal aorta. In addition, aortic mRNA transcripts of RelA-dependent cytokines IL-6 and IL-1β were significantly elevated suggesting that Ang II functionally activates RelA signaling. To test the role of mesenchymal RelA in AAA formation, we generated RelA-CKO mice by administering tamoxifen to double transgenic mice harboring RelA-flox alleles and tamoxifen-inducible Col1a2 promoter-driven Cre recombinase (Col1a2-CreERT). Tamoxifen administration to Col1a2-CreERT·mT/mG mice induced Cre expression and RelA depletion in aortic smooth muscle cells and fibroblasts but not in endothelial cells. Infusion of Ang II significantly increased abdominal aortic diameter and the incidence of AAA in RelA wild-type but not in RelA-CKO mice, independent of changes in systolic blood pressure. Furthermore, mesenchymal cell-specific RelA-CKO mice exhibited decreased expression of IL-6 and IL-1β cytokines and decreased recruitment of C68+ and F4/80lo·Ly6Chi monocytes during Ang II infusion. Conclusions - Fibrogenic mesenchymal RelA plays a causal role in Ang II-induced vascular inflammation and AAA in normolipidemic mice.

Original languageEnglish (US)
Pages (from-to)1881-1890
Number of pages10
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number10
StatePublished - 2017


  • Abdominal
  • Angiotensin II
  • Animals
  • Aortic aneurysm
  • Blood pressure
  • Interleukin-6

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Deletion of NF-κB/RelA in angiotensin II-sensitive mesenchymal cells blocks aortic vascular inflammation and abdominal aortic aneurysm formation'. Together they form a unique fingerprint.

Cite this