Depletion of CD11c+ dendritic cells in apolipoprotein E-deficient mice limits angiotensin II-induced abdominal aortic aneurysm formation and growth

Objective: The role of chronic inflammation in abdominal aortic aneurysm (AAA) is controversial. CD11c(+) antigen-presenting cells (APCs) (dendritic cells (DCs)) have been reported in human AAA samples but their role is unclear. The effect of conditional depletion of CD11c(+) cells on experimental AAA was investigated in the angiotensin II (AngII)-infused apolipoprotein E-deficient (ApoE(-/-)) mouse model. Approach: CD11c-diphtheria toxin (DT or D.tox) receptor (DTR), ovalbumin (OVA) fragment as 140-386, and enhanced green fluorescent protein (eGFP)-ApoE(-/-) (CD11c.DOG.ApoE(-/-)) mice were generated and CD11c(+) cell depletion achieved with D.tox injections (8 ng/g body weight, i.p., every-other-day). AAA formation and growth were assessed by measurement of supra-renal aortic (SRA) diameter in vivo by serial ultrasound and by morphometry assessment of harvested aortas at the end of the study. Results: Depletion of CD11c(+)cells by administration of D.tox on alternative days was shown to reduce the maximum diameter of AAAs induced by 28 days AngII infusion compared with controls (D.tox, 1.58 +/- 0.03 mm vs Vehicle control, 1.81 +/- 0.06 mm, P<0.001). CD11c(+) depletion commencing after AM establishment by 14 days of Angll infusion, was also shown to lead to smaller AAAs than controls after a further 14 days (D.tox, 1.54 +/- 0.04 2. mm vs Vehicle control, 1.80 +/- 0.03 mm, P<:0.001). Flow cytometry revealed significantly lower numbers of circulating CD44(hi) CD62L(lo) effector CD4 T cells, CD44(hi) CD62L(lo )effector CD8 T cells and B220(+) B cells in CD11c(+) cell-depleted mice versus controls. CD11c(+) depletion attenuated SRA matrix degradation indicated by decreased neutrophil elastase activity (P=0.014), lower elastin degradation score (P=0.002) and higher collagen content (P=0.002). Conclusion: CD11c(+) cell-depletion inhibited experimental MA development and growth associated with down-regulation of circulating effector T cells and attenuated matrix degradation. The findings suggest involvement of autoreactive immune cells in AAA pathogenesis.