Non-ACE Pathway-induced Angiotensin II Production

For the past century, the renin–angiotensin system (RAS) has been recognized as one of the major blood pressure-regulating systems. Angiotensin II (Ang II) is the final physiologically active product of RAS, and it works not only as a strong vasopressor but also as a promotor of tissue remodeling in various organs such as heart, arteries, and kidneys. RAS is the predominant pathway of Ang II formation in human plasma, but not in the tissues. There are several alternative pathways producing angiotensin II in human tissues, and they are involved in structural remodeling of the cardiovascular system. Proteinases such as chymase, kallikrein, cathepsin G, and elastase- 2 are probably responsible for angiotensin-converting enzyme (ACE)-independent Ang II formation in human tissues. In particular, chymase is an important Ang II-generating enzyme in the human heart. It is important to elucidate the mechanisms of the ACEindependent Ang II formation in human tissues; long-term inhibition of the local Ang II formation may become one of the strategies to prevent cardiovascular remodeling. Keywords: Local renin–angiotensin system, angiotensin II, ACE, chymase, elastase-2, angiotensin-(1–12), cardiovascular disease.