The Vasoactive Peptide Angiotensin-(1–7), Its Receptor Mas and the Angiotensin-converting Enzyme Type 2 are Expressed in the Human Endometrium

Abstract

Angiotensin (Ang)-(1-7) is one of the major active components of the renin-angiotensin system, produced from cleavage of Ang II by angiotensin-converting-enzyme type 2 (ACE2), which acts through a specific G protein-coupled receptor, Mas. We have investigated whether the human endometrium expresses these components during menstrual cycle. By radioimmunoassay, Ang-(1-7) was detected in endometrial wash fluid at picomolar concentrations. Using immunofluorescence, both the peptide and its receptor were identified in cultured endometrial epithelial and stromal cells. By immunohistochemistry, Ang(1-7) was localized in the endometrium throughout menstrual cycle, being more concentrated in the glandular epithelium of mid- and late secretory phase. This pattern corresponded to the ACE2 mRNA, which was more abundant in epithelial cells than in stromal cells (2-fold increase, p < 0.05) and in the secretory vs. proliferative phase (6.6-fold increase, p < 0.01). The receptor Mas was equally distributed between epithelial and stromal cells and did not change during menstrual cycle. The physiological role of this peptide system in normal and pathological endometrium warrants further investigation.

Angiotensin-(1-7), its receptor Mas, and the angiotensin-converting enzyme type 2 are expressed in the human ovary

“…The paraffin-embedded ovarian specimens were cut into 4-mm sections and processed by the avidin-biotin-peroxidase method as previously described (20,21). For Mas immunoreactivity, antigenic recovery was obtained by treatment with L.A.B.…”

The Changes of Serum Angiotensin-Converting Enzyme 2 in Patients with Pulmonary Arterial Hypertension due to Congenital Heart Disease

“…Angiotensin-converting enzyme 2 (ACE2), a homolog of ACE, is a carboxypeptidase that degrades angiotensin (Ang) II to Ang-(1-7) [3,4]. ACE2 plays an important role in the vasoprotective axis (ACE2-Ang-(1-7)-Mas axis) of the renin angiotensin system (RAS) and counterbalances the vasoconstrictive, proliferative and fibrotic axes [ACE-Ang II-Ang II type 1 receptor (AT1R) axis] of the RAS [5,6,7].…”

The Expression of MAS1, an Angiotensin (1–7) Receptor, in the Eutopic Proliferative Endometria of Endometriosis Patients

“…In the endometriosis patients, MAS1 expression was especially evident in the proliferative tissues but was rarely apparent in the secretory tissues. Vaz-Silva et al [14] have immunohistochemically shown that MAS1 was located in normal endometrial tissues from all phases of the menstrual cycle and that the intensity of MAS1 staining did not change during the menstrual cycle. In our study, MAS1 expression in the normal endometrium was barely detected by RT-qPCR, whatever the menstrual cycle phase is.…”

“…Our data for the MAS1/AT1 ratio suggested a notable phenomenon. Recently, the notion that the RAS can act through 2 opposing arms, the main ACE-angiotensin II-AT1 axis and the ACE2-angiotensin (1-7)-MAS1 axis [14], has become well accepted. Angiotensin (1-7) has anti-angiogenic and growth-inhibitory effects on the endothelium [22].…”

“…We have demonstrated that both AT1 and AT2 receptors are expressed in endometriosis and the ratio of the AT1/AT2 mRNA levels is increased in an endometriosis-specific manner [13], suggesting that the AT1 pathway contributes to the pathogenesis of endometriosis at ectopic sites [13,14]. In this study, we focused on the MAS1 pathway in the endometria of endometriosis patients.…”