Mechanisms of the Renin Angiotensin System Influencing Atherosclerosis

This chapter focuses on recent mechanistic studies in animal models. Genetic manipulation and pharmacological approaches strongly enhance the understanding on how the Renin Angiotensin System (RAS) influences atherosclerosis. The chapter updates the current knowledge regarding the roles of cell-specific manipulation of the RAS components on atherosclerosis and molecules that influence atherosclerosis via activation of Angiotensin II (Angll). Using hypercholesterolemic mouse models with chronic AngII infusion (typically 0.5 or 1 μg/kg/min for 4 weeks), many potential molecular mechanisms by which the bioactive angiotensin peptide promotes atherosclerosis are studied. The chapter also provides impressively consistent demonstrations that activation of AngII augments atherosclerosis, while inhibition of renin, Angiotensin converting enzyme (ACE), or AT1 receptor attenuates atherosclerosis in animal models. The feedback loop formed between animal experiments and clinical trials will continuously be a powerful approach to enhance knowledge of the complex disease and provide mechanistic base in improving current therapeutic strategies.