Placental ACE2 Expression: A Possible Pathogenetic Mechanism for Infantile Hemangiomas

ACE2 is a mono-carboxypeptidase with remarkable vasculo-protective properties, and its expression in the human placenta plays a central role in blood pressure homeostasis and fetal perfusion. Therefore, an alteration in the placental expression of ACE2 could be responsible for reduced placental perfusion and infantile hemangioma (IH) development. Study placentae were collected from patients affected by IHs who were referred to our Dermatology Clinic from 2016 to 2022, while control placentae were randomly collected while matching cases for gestational age. Immunohistochemical investigations were performed with a recombinant anti-ACE2 rabbit monoclonal antibody. A total of 47 placentae were examined, including 20 study placentae and 27 control ones. The mean placental weight was significantly lower in the study group (380.6 g vs. 502.3 g; p = 0.005), while subclinical chorioamnionitis occurred more frequently in the study group (20% vs. 0%, p = 0.03). The mean ACE2 expression was dramatically lower in the study group (χ2 = 42.1 p < 0.001), and the mean placental weight was significantly lower when ACE2 was not expressed compared to the 25-75% and >75% classes of expression (p < 0.05). This study demonstrated that ACE2, as a marker for tissue hypoxia, is dramatically hypo-expressed in placentae belonging to mothers who delivered one or more babies with IH compared to the controls.