Does the combination of a renin inhibitor with a statin have potential for improved inhibition of atherosclerosis?

Abstract

The concept that pharmacological inhibition of the renin–angiotensin–aldosterone system (RAAS) can reduce atherosclerosis is now well established [1]. In addition to the considerable evidence that components of the RAAS stimulate lesion development, targeting different components of the system has been shown to both reduce lesion formation and to increase markers of plaque stability. For example, in atherosclerosis-prone mice, administration of angiotensin II (Ang II) over long periods promotes lesion formation, whereas angiotensinconverting enzyme (ACE) inhibition, angiotensin 1 receptor antagonism [2] or mineralocorticoid receptor antagonism [3] reduces lesion size. An increasing body of evidence suggests that both Ang II-induced stimulation of lesion formation and the antiatherosclerotic effects of treatment (ACE inhibition/AT1 receptor antagonism) are independent of blood pressure; indicating a direct atherosclerotic effect of Ang II on the cells of the vascular wall. However, the exact mechanisms through which blockade of the RAAS alters lesion formation remain unclear.