The Renin-Angiotensin-Aldosterone System: Genomics, Proteomics and Therapeutic Implications

Abstract

Since its discovery in 1898, the renin-angiotensin-aldosterone system (RAAS) has been intensely studied in the medical community, which led to important breakthroughs concerning the treatment of heart diseases. The main role of RAAS is to maintain the circulatory homeostasis, by maintaining the fluid volume. Angiotensin II (ANG II) can act on two receptors: angiotensin type 1 and angiotensin type 2 (AT1R and AT2R). The effect of AT1R consists in increased sodium retention, promotes vasoconstriction (mostly on the efferent arteriole), induces sympathetic nervous system activity, determines thirst and promotes the release of aldosterone. Abnormal activation of RAAS will determine hypertension and cardiac hypertrophy that may lead to heart failure. This is the reason why the pharmacological inhibition of this system has proven to induce such a beneficial effect in cardiovascular diseases such as hypertension and congestive heart failure. Later studies of patients with coronary artery disease revealed that angiotensin-converting enzyme (ACE) gene is also involved in the process of atherosclerosis and those mutations in its gene account for an increased susceptibility to severe acute coronary events. The most common ACE gene mutation is represented by deletions and insertions in the 16th intron (presence or absence of the 287-bp Alu repeat sequence), resulting in three possible genotypes, identified by the length of the fragments: II (490 bp), ID (490, 190 bp) and DD (190 bp). Scientific evidence suggests that the D allele plays a major role in the determination of coronary artery disease. The next step would be to develop new treatment strategies according to the genetic background of each patient.