SCIENCE@home

Loss of vascular smooth muscle cell autophagy exacerbates angiotensin II‐associated aortic remodeling

Azza Ramadan,Krishna K Singh,A. Quan,P. Plant,M. Al-Omran,H. Teoh,S. Verma

Published 2017 in Journal of Vascular Surgery

ABSTRACT

Objective The pathophysiologic processes of abdominal aortic aneurysms (AAAs) and atherosclerosis often intersect. Given that anomalies in vascular smooth muscle cell (SMC) autophagy have been noted in models of atherosclerosis, we sought to evaluate the potential role that SMC autophagy may play in the initiation and progression of AAAs. Methods Studies were conducted in ATG7flx/flx SM22&agr;‐Cretg/+ (SMC ATG7 knockout [SMC‐ATG7‐KO]) and ATG7WT/WT; SM22&agr;‐Cretg/+ (SMC ATG7 wild‐type [SMC‐ATG7‐WT]) littermates that were continuously infused with angiotensin II (Ang II; 1.5 mg/kg/d) for up to 12 weeks. Mortality, morbidity, hemodynamics, and aortic remodeling were documented. Results During the 12‐week observation window, all of the Ang II‐treated SMC‐ATG‐WT mice (n = 6) survived, whereas 10 of the 19 Ang II‐treated SMC‐ATG‐KO mice had died by week 7 (log‐rank test, P < .001). Mean arterial pressure (128.07 ± 3.4 mm Hg for Ang II‐treated SMC‐ATG‐KO vs 138.5 ± 5.87 mm Hg for Ang II‐treated SMC‐ATG‐WT mice) and diastolic arterial pressure (109.7 ± 2.55 mm Hg for Ang II‐treated SMC‐ATG7‐KO vs 119.4 ± 2.12 mm Hg for Ang II‐treated SMC‐ATG7‐WT mice) were significantly different between the two groups (P < .01). Cardiac rupture, myocardial infarct, end‐organ damage, pleural effusion, and venous distention were noted in Ang II‐treated SMC‐ATG7‐KO but not in Ang II‐treated SMC‐ATG7‐WT mice. Although the suprarenal aortic diameters of the Ang II‐treated SMC‐ATG7‐KO group demonstrated a trending increase (at week 4, 1.26 ± 0.06 mm [n = 14] for Ang II‐treated SMC‐ATG‐KO mice vs 1.09 ± 0.02 mm [n = 5] for Ang II‐treated SMC‐ATG‐WT mice; P < .05), only 2 of the 19 developed abdominal aortic dissections. Conclusions Mice with SMC ATG7 deficiency that are chronically infused with Ang II do not tend to develop dissecting AAA but do exhibit adverse aortic remodeling and appreciable cardiac failure‐associated mortality. Clinical Relevance Although loss of smooth muscle cell ATG7 had little impact on the development and progression of an experimental model of abdominal aortic aneurysm, it did promote both adverse aortic remodeling and cardiac failure‐associated mortality.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-41 of 41 references · Page 1 of 1

CITED BY

Showing 1-37 of 37 citing papers · Page 1 of 1