Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E–deficient mice

Abstract

Figure 1Arterial blood pressure determined using a catheter in the femoral artery of anesthetized apoE -/-mice. Mice were anesthetized after 28 days of infusion of vehicle or the stated dose of Ang II. Points represent the mean of at least seven observations, and bars represent SEM.

Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE −/− Mice With Unilateral Renal Artery Stenosis

“…Lipid deposition, as determined by Oil Red O staining, was detected in 11.6% [6.1, 14.2] of the area of the aortic arch in the sham surgery group, similar to results from past studies in chow‐fed ApoE −/− mice (Figure 3A and 3B) 6, 22. Chronic RAS resulted in an approximate 3‐fold increase in lipid staining in the aortic arch compared to sham surgery (33.2% [24.4, 47.5] vs 11.6% [6.1, 14.2]; P <0.05).…”

“…These lesions progress with age in chow‐fed mice, such as used in the present study. Interventions such as a high‐fat, high‐cholesterol diet,20 infusion of Ang II,6, 8 and unilateral RAS10, 11, 16, 21 have been shown to accelerate lipid deposition in this area.…”

“…One potential explanation for the lack of benefit in these trials is that renal ischemia causes irreversible atherogenic changes and that restoration of renal blood flow has no effect on mitigating the damage to the vasculature 4. Biological plausibility of this hypothesis is provided by numerous studies showing that decreased renal perfusion is associated with RAS activation,5 and data from animal models showing that even short‐term elevation in angiotensin II (Ang‐II) levels can accelerate the development of atherosclerosis and lead to changes in the arterial wall that persist even after Ang‐II levels return to baseline 6, 7, 8, 9, 10, 11. In addition, RAS has been shown to result in elevated oxidative stress, sympathoadrenergic activation, and impaired vasoactive responses, both within the kidney and the systemic microcirculation 12, 13…”

Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling

“…Much remains unknown about ATAA pathology, largely because of the wide heterogeneity underlying these abnormalities. Nevertheless, most aortic aneurysms are associated with augmented angiotensin II (AngII) activity,6, 7, 8 and AngII‐infusion murine models have been established for both ATAA and abdominal aortic aneurysm (AAA) 9, 10, 11…”

Système rénine-angiotensine et remodelage vasculaire

“…L'angiotensine II induit une dégranulation partielle des polymorphonucléaires neutrophiles, ainsi que la production d'ions superoxydes et la sécrétion de leucotriènes. Un exemple de cet effet sur les leucocytes a été apporté par une étude menée chez des souris invalidées pour le gène de l'apolipoprotéine E (Apo E -/-), donc susceptibles à l'athérosclérose: la perfusion directe d'angiotensine II n'induit qu'une augmentation très limitée de la pression artérielle, mais provoque la formation d'ané-vrismes de l'aorte [31]. Ces derniers sont associés à une disparition des cellules musculaires lisses artérielles, à une destruction de la matrice extracellulaire et à une infiltration importante de cellules inflammatoires productrices de protéases (activateurs du plasminogène, métalloprotéinases) [32].…”