Renin inhibition with aliskiren profoundly reduced atherosclerotic lesion size in the aortic root of fat-fed Ldlr-/- mice in a dose-dependent manner compared to vehicle (p<0.0001).
Does renin inhibition with aliskiren reduce atherosclerotic lesion size in fat-fed Ldlr(-/-) mice?
Systemic renin inhibition with aliskiren profoundly reduces hypercholesterolemia-induced atherosclerosis in mice, independent of blood pressure reduction.
Absolute Event Rate: 0.05% vs 0.16%
p-value: p=<0.0001
The role of the renin angiotensin system (RAS) in atherosclerosis is complex because of the involvement of multiple peptides and receptors. Renin is the rate-limiting enzyme in the production of all angiotensin peptides. To determine the effects of renin inhibition on atherosclerosis, we administered the novel renin inhibitor aliskiren over a broad dose range to fat-fed LDL receptor-deficient (Ldlr(-/-)) mice. Renin inhibition resulted in striking reductions of atherosclerotic lesion size in both the aortic arch and the root. Subsequent studies demonstrated that cultured macrophages expressed all components of the RAS. To determine the role of macrophage-derived angiotensin in the development of atherosclerosis, we transplanted renin-deficient bone marrow to irradiated Ldlr(-/-) mice and observed a profound decrease in the size of atherosclerotic lesions. In similar experiments, transplantation of bone marrow deficient for angiotensin II type 1a receptors failed to influence lesion development. We conclude that renin-dependent angiotensin production in macrophages does not act in an autocrine/paracrine manner. Furthermore, in vitro studies demonstrated that coculture with renin-expressing macrophages augmented monocyte adhesion to endothelial cells. Therefore, although previous work suggests that angiotensin peptides have conflicting effects on atherogenesis, we found that renin inhibition profoundly decreased lesion development in mice.
Lü et al. (2008) studied Hypercholesterolemia-induced atherosclerosis (n=51). Aliskiren vs. Vehicle (PBS) was evaluated on Atherosclerotic lesion size in the aortic root (p=<0.0001). Renin inhibition with aliskiren profoundly reduced atherosclerotic lesion size in the aortic root of fat-fed Ldlr-/- mice in a dose-dependent manner compared to vehicle (p<0.0001).