To date, the only known biological function of ACE3 is that it functions as an IZUMO‐interacting protein (IZUMO is an essential sperm protein for sperm‐egg fusion) involved in the acrosome reaction in sperm. 8 ACE3 has one single functional domain (the zinc‐binding motif), and the most important catalytic Glu in this motif is substituted by Gln, which indicates that ACE3 should lack the catalytic activity as a zinc metalloprotease. Recently, a new component of the ACE family was identified and characterized through bioinformatics analyses, termed ACE3. 5, 6, 7 However, the underlying mechanisms during the development of cardiac hypertrophy are rather complicated and remain to be completely discovered. 2, 3, 4 Numerous signal transduction pathways have been studied in the hypertrophic process, such as the PI3K/AKT/GSK3β pathway, the calcineurin/nuclear factor of activated T cells (NFAT) pathway, and the mitogen‐activated protein kinase (MAPK) pathway.

Although the initial hypertrophic phase is indeed compensatory to maintain cardiac output, the beneficial effects are contravened by sustained pathological hypertrophy, which eventually results in malignant arrhythmia, heart failure, and sudden death.

1 Cardiac hypertrophy is usually characterized by the enlargement of cardiomyocytes, an increase in protein synthesis, the reorganization of sarcomeres and the reactivation of the fetal gene program. Analyses of the underlying molecular mechanism revealed that ACE3‐mediated protection against cardiac hypertrophy by suppressing the activation of mitogen‐activated protein kinase kinase ( MEK)‐regulated extracellular signal‐regulated protein kinase ( ERK1/2) signaling, which was further evidenced by the observation that inhibition of the MEK‐ ERK1/2 signaling by U0126 rescued the exacerbated hypertrophic phenotype in ACE3‐deficient mice.Ĭardiac hypertrophy develops as an adaptive response to an increased workload induced by diverse pathological stimuli, eg, hypertension, aortic stenosis, and valvular diseases. Our data demonstrated that ACE3‐deficient mice exhibited more pronounced cardiac hypertrophy and fibrosis and a strong decrease in cardiac contractile function, conversely, cardiac‐specific ACE3‐overexpressing mice displayed an attenuated hypertrophic phenotype, compared with control mice, respectively. Cardiac hypertrophy in mice was induced by aortic banding ( AB) and the extent of hypertrophy was analyzed through echocardiographic, pathological, and molecular analyses. In cultured cardiomyocytes, ACE3 conferred protection against angiotensin II (Ang II)‐induced hypertrophic growth.

Neonatal rat cardiomyocytes ( NRCMs) with gain and loss of function of ACE3 and mice with global knockout or cardiac‐specific overexpression of ACE3 were used in this study.

Ace 3 medical system