Subcellular characteristics of functional intracellular renin–angiotensin systems

• Published in: Peptides (New York, N.Y. : 1980) Vol. 38; no. 2; pp. 437 - 445
• Main Authors: Abadir, Peter M., Walston, Jeremy D., Carey, Robert M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2012
• Subjects: Angiotensin peptides; Angiotensin receptors; angiotensinogen; Angiotensins - metabolism; Animals; Cardiovascular disease; chronic diseases; functional properties; Humans; Hypertension; Intracellular; peptidyl-dipeptidase A; receptors; renin; Renin - metabolism; Renin-Angiotensin System; tissues; Renin–angiotensin system; Hypertension; Angiotensin peptides; Cardiovascular disease; Intracellular; Angiotensin receptors
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2012.09.016

► Compelling evidence now exists for complete, independent, differentially regulated intracellular renin–angiotensin systems in many tissues. ► Angiotensinogen, the enzymes renin and angiotensin converting enzyme and angiotensin peptides can be synthesized and retained intracellularly. ► Angiotensin receptors (AT1 and AT2) are abundant intracellularly mainly at the nuclear and mitochondrial levels. ► Functional intracellular renin–angiotensin system units have been documented both in nuclei and mitochondria. The renin–angiotensin system (RAS) is now regarded as an integral component in not only the development of hypertension, but also in physiologic and pathophysiologic mechanisms in multiple tissues and chronic disease states. While many of the endocrine (circulating), paracrine (cell-to-different cell) and autacrine (cell-to-same cell) effects of the RAS are believed to be mediated through the canonical extracellular RAS, a complete, independent and differentially regulated intracellular RAS (iRAS) has also been proposed. Angiotensinogen, the enzymes renin and angiotensin-converting enzyme (ACE) and the angiotensin peptides can all be synthesized and retained intracellularly. Angiotensin receptors (types I and 2) are also abundant intracellularly mainly at the nuclear and mitochondrial levels. The aim of this review is to focus on the most recent information concerning the subcellular localization, distribution and functions of the iRAS and to discuss the potential consequences of activation of the subcellular RAS on different organ systems.