Depletion of CD11c+ dendritic cells in apolipoprotein E-deficient mice limits angiotensin II-induced abdominal aortic aneurysm formation and growth. (12th November 2019)

• Record Type: Journal Article
• Authors: Krishna, Smriti M.; Moran, Corey S.; Jose, Roby J.; Lazzaroni, Sharon; Huynh, Pacific; Golledge, Jonathan
• Is Part Of: Clinical science. Volume 133:Number 21(2019)
• Page Start: 2203
• Page End: 2215
• Publication Date: 2019-11-12
• Subjects: Abdominal aortic aneurysm -- angiotensin II -- Apolipoprotein E -- dendritic cells -- neutrophil elastase; Medicine -- Periodicals; Biochemistry -- Periodicals; 616
• DOI: 10.1042/CS20190924
• Languages: English
• ISSNs: 0143-5221

Abstract

Abstract: 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 (D TR), ovalbumin (O VA) fragment aa 140–386, and enhanced green fluorescent protein (eG FP)- 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 AAA establishment by 14 days of AngII infusion, was also shown to lead to smaller AAAs than controls after a further 14 days ( D.tox, 1.54 ± 0.04 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=0.012 ) and higher collagen content ( P=0.002 ). Conclusion: CD11c + cell-depletion inhibited experimental AAA 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.