Beyond blood pressure, fluid and electrolyte homeostasis – Role of the renin angiotensin aldosterone system in the interplay between metabolic diseases and breast cancer

The classical renin angiotensin aldosterone system (RAAS), as well as the recently described counter-regulatory or non-canonical RAAS have been well characterized for their role in cardiovascular homeostasis. Moreover, extensive research has been conducted over the past decades on both paracrine and the endocrine roles of local RAAS in various metabolic regulations and in chronic diseases. Clinical evidence from patients on RAAS blockers as well as pre-clinical studies using rodent models of genetic manipulations of RAAS genes documented that this system may play important roles in the interplay between metabolic diseases and cancer, namely breast cancer. Some of these studies suggest potential therapeutic applications and repurposing of RAAS inhibitors for these diseases. In this review, we discuss the mechanisms by which RAAS is involved in the pathogenesis of metabolic diseases such as obesity and type-2 diabetes as well as the role of this system in the initiation, expansion and/or progression of breast cancer, especially in the context of metabolic diseases.