The Role of Angiotensin-Converting Enzyme in Hypertension

Angiotensin-converting enzyme (ACE) is a zinc-metalloendopeptidase with two catalytically active sites (N- and C-terminal catalytic domains) responsible for converting angiotensin-I into the vasoconstrictor angiotensin-II. It is encoded by ?21 kb long ACE gene, located on 17q23.3 (ENSEMBL ID: ENSG00000159640, NCBI gene ID: 1636). This gene consists of 26 exons and encodes 2 transcript variants (somatic ACE and germinal ACE). However, ACE is a relatively nonspecific peptidase that is capable of cleaving a wide range of substrates. ACE and its peptide substrates and products affect many physiologic processes, such as blood pressure control, hematopoiesis, reproduction, renal development, renal function, and the immune response. Hypertension is a condition where the blood vessels have persistently raised pressure. According to the World Health Organization, hypertension is an important factor in cardiovascular diseases. ACE is a key factor in the regulation of the renin-angiotensin-aldosterone system (RAAS), it catalyzes the formation of angiotensin-II and the deactivation of bradykinin in the renin-angiotensinaldosterone and kallikrein-kinin systems. Also, the ACE gene polymorphisms have been suggested to be linked to increasing risk of hypertension. However, the results are still controversial. This chapter focuses on updates in our understanding of the RAAS, ACE Insertion/deletion polymorphism and the relation of ACE and ACE2 in hypertension.