s Classical and New Renin-Angiotensin Signalling in Atherosclerosis

Renin-angiotensin system (RAS) plays many roles in human physiology and its abnormal activation is certainly involved in various cardiovascular diseases such as hypertension and atherosclerosis: this is repeatedly confirmed by trials with RAS blockers in different clinical situations. In the last decade the classical circulating RAS has been flanked by new pathways with recently discovered players demonstrating not only an endocrine system, but also a paracrine and an intracrine system. New receptors (AT2, Mas, AT4, and receptor for renin and prorenin), new enzymes (angiotensinconverting enzyme 2, endopeptidase, aminopeptidases), new angiotensins (angiotensin III, angiotensin IV, angiotensin-[1- 7]) have been found. The most intriguing new aspect is represented by the presence of pathways which exert opposite effects with respect to the renin-angiotensin-AT1 receptor pathway: therefore it seems that RAS has an internal way to counterbalance the potentially negative actions. Atherosclerosis, the main cause of death in western countries, is a chronic inflammatory disorder at the vascular level with a well established sequence of cellular and tissue activation. The favourable modulation of RAS may represent a new and very promising way to interfere with the atherosclerotic process. The present review will try to give a complete update of RAS with its new and diverse physiological functions and will suggest the targets for the development of new drugs devoted to an effective prevention of cardiovascular atherosclerotic events.