A new addition to the renin-angiotensin peptide family: proAngiotensin-12 (PA12)

The renin–angiotensin system (RAS) is a pivotal physiological regulator of cardiovascular homeostasis, potently impacting hydroelectrolyte balance, arterial tone, and blood pressure as well as modulating the growth and differentiation of vascular smooth muscle cells and cardiac myocytes. In contrast, dysregulation of the RAS is intrinsically associated with cardiovascular pathologies such as hypertension, myocardial infarction, and coronary heart disease.1 The conversion of angiotensinogen to angiotensin-I (AngI, Ang1–10) by kidney-derived renin, followed by AngI conversion to AngII (Ang1–8) through angiotensin-converting enzyme type-1 (ACE1), represents the principal biochemical axis within this cascade. AngII, the main effector peptide of the RAS, subsequently exerts its broad spectrum of effects primarily through stimulation of AngII-specific AT1 receptors (AT1R), although AngII interaction with AT2 receptors (AT2R), leading to effects opposing those stemming from AT1R-mediated activation, has also been reported.2,3 Over the years, the functional complexity of the RAS cascade has gradually expanded to encompass additional processing enzymes (thimet oligopeptidase, neprilysin, prolyl oligopeptidase), ACE homologues (ACE2) and other biologically active angiotensin fragments such as AngIII (Ang2–8), AngIV (Ang3–8), and Ang-(1–7) (Ang1–7). The latter heptapeptide, in particular, has been the focus of unprecedented attention during the last decade, with extensive evidence supporting vasodilatory and anti-mitogenic roles for Ang-(1–7) within the cardiovascular system, effectively antagonizing the cardiovascular actions of AngII.4,5