Evolution of angiotensin II-mediated atherosclerosis in ApoE KO mice

J. Cha, V. Ivanov, S. Ivanova, T. Kalinovsky, M. Rath, A. Niedzwiecki

Molecular Medicine Reports, 2010, 3:565-570

The dysregulation of renin-angiotensin system signaling is a contributing factor to the development of atherosclerosis and cardiovascular disease. We studied a progression of angiotensin II (AngII)-induced arterial wall atherosclerosis after its induction. Atherosclerosis was accelerated in ApoE (-/-) C57B6 mice by 4 weeks of continuous osmotic pump administration of AngII at 23 nmol/24 h. Changes in aortae were evaluated at 4 and 16 weeks after pump installation, as well as in mice without AngII administration. AngII supplementation induced additional lesions in the aortic arch and its vessels 4 weeks after pump installation showing that AngII had taken effect in comparison to non-AngII controls.

These observations were both grossly visible and confirmed through histology. Additionally, the angiotensin II-mediated injuries continued to accelerate great vessel atherosclerosis after AngII discontinuation at 4 weeks. Atherosclerosis in ApoE KO mice post 16 weeks AngII administration was over 3-fold greater than indicated by the difference in lesion development between ApoE KO mice post 4 weeks AngII and age-matched control ApoE KO mice. While lesion size after 12 weeks AngII cessation (post 16-weeks AngII group) increased 249% compared to post 4 weeks AngII, the rate of lesion formation between post 4 weeks AngII and non-AngII groups indicate a 70% increase with a linear relationship with time. Aortic dissections were present at 4 weeks post AngII pump installation at high frequency compared to unsupplemented controls where they were absent. Surprisingly, aortic dissections were absent at 16 weeks post AngII, indicating a healing process. The study suggests that excessive AngII initiates a cascade of pathological biochemical events and plaque evolution that does not cease even after its removal.

atherosclerosis; angiotensin II; ApoE KO mice; aortic dissection

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