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. 2014 Apr 1;9(4):e87845. doi: 10.1371/journal.pone.0087845

Figure 7. Hypothetic model for RAS regulation in heart failure.

Figure 7

Angiotensin I (AngI) is being converted to angiotensin II (AngII) by angiotensin converting enzyme (ACE). AngII is further metabolized to angiotensin 1–7 (Ang-(1–7)) by sACE2. AngII binds to and activate the type 1 AngII receptors (AT1R), while Ang-(1–7) binds to and activate the Mas receptor. Levels of tissue located and soluble forms of these enzymes determine local levels of angiotensin peptides. We hypothesize that a significant redistribution of tissue and soluble ACE and ACE2 occurs in human heart failure which changes are reversible upon improvement of the cardiac function. In particular, sACE2 limits AngII levels under healthy conditions, resulting in a low level of ATR1 stimulation and high Mas receptor stimulation, a condition which is beneficial in cardiovascular physiology. However, ACE2 is probably re-distributed in imminent or definitive heart failure. As a result, its activity increases in the circulating blood, but decreases in the tissues. This result in higher local Ang II levels, higher AT1R stimulation and lower Mas receptor activation. These latter features being characteristic to heart failure.