Angiotensin-converting enzymes and drug discovery in cardiovascular diseases

Abstract

Angiotensin-converting enzyme (ACE) is a major target in the treatment of cardiovascular diseases (CVDs). In addition to ACE, ACE2 - which is a homolog of ACE and promotes the degradation of angiotensin II (Ang II) to Ang (1-7) - has been recognized recently as a potential therapeutic target in the management of CVDs. This article reviews different metabolic pathways of ACE and ACE2 (Ang I-Ang II-AT1 receptors and Ang I-Ang (1-7)-Mas receptors) in the regulation of cardiovascular function and their potential in new drug development in the therapy of CVDs. In addition, recent progress in the study of angiotensin and ACE in fetal origins of CVD, which might present an interesting field in perinatal medicine and preventive medicine, is briefly summarized.

Figure 1

Angiotensinogen is transformed to Ang I by renin and subsequently converted by ACE into Ang II or by ACE2 into Ang (1–7). ACE2 also cleaves Ang I to Ang (1–9), which is further converted by ACE into Ang (1–7). Ang II acting on AT1R leads to physiological or pathophysiological activities. Acting on Mas receptors, Ang (1–7) might attenuate the actions of the ACE-Ang II-AT1R axis. Solid or dashed lines indicate positive or negative effects, respectively. ACE, angiotensin-converting enzyme; AT1R, angiotensin II type 1 receptor; Mas, Ang (1–7) receptor; ACE-I, ACE inhibitor; ARB, AT1R blocker.