The mono-carboxypeptidase Angiotensin-Converting Enzyme 2 (ACE2) is an important player of the renin-angiotensin system (RAS). ACE2 is also the receptor for SARS-CoV-2, the new coronavirus that causes COVID-19. It has been hypothesized that following SARS-CoV-2/ACE2 internalization Ang II level would increase in parallel to a decrease of Ang-(1-7) in COVID-19 patients. In this preliminary report, we analyzed the plasma levels of angiotensin peptides in 19 severe COVID-19 patients and 19 non-COVID-19 volunteers. Unexpectedly, a significant increase in circulating Ang-(1-7) and lower Ang II plasma level were found in critically ill COVID-19 patients. Accordingly, an increased Ang-(1-7)/ Ang II ratio was observed in COVID-19 suggesting a RAS dysregulation toward an increased formation of Ang-(1-7) in these patients.

In 2020 we are celebrating the 20th anniversary of the angiotensin-converting enzyme 2 (ACE2) discovery. This event was a landmark that shaped the way that we see the renin–angiotensin system (RAS) today. ACE2 is an important molecular hub that connects the RAS classical arm, formed mainly by the octapeptide angiotensin II (Ang II) and its receptor AT1, with the RAS alternative or protective arm, formed mainly by the heptapeptides Ang-(1-7) and alamandine, and their receptors, Mas and MrgD, respectively. In this work we reviewed classical and modern literature to describe how ACE2 is a critical component of the protective arm, particularly in the context of the cardiac function, coagulation homeostasis and immune system. We also review recent literature to present a critical view of the role of ACE2 and RAS in the SARS-CoV-2 pandemic.

The monocarboxypeptidase angiotensin-converting enzyme 2 (ACE2) is a major player in the the renin–angiotensin system (RAS) as it converts the decapeptide angiotensin (Ang) I to Ang-(1–9) and Ang II to Ang-(1–7) (figure 1a) [1]. ACE2 is also a target for the new human coronavirus SARS-CoV-2, which is responsible for the dramatic ongoing COVID-19 pandemic [2]. It has been suggested that following SARS-CoV-2/ACE2 internalisation, Ang II level increases [3] in parallel to a decrease of Ang-(1–7) level [4]. These changes would be expected both at tissue and circulatory levels. Considering that Ang-(1–7) has many beneficial effects, including anti-inflammatory, antithrombogenic and antifibrotic activities [1], it has been hypothesised that Ang-(1–7) administration would improve the clinical outcome of COVID-19 patients. Aiming to test this hypothesis, a phase I/II clinical trial (www.clinicaltrials.gov identifier NCT04633772) has been initiated with a planned phase III clinical trial (NCT04332666).

N euroiNterveNtioNal procedures have become a significant asset in the treatment of cerebrovascular disorders. Training in these techniques requires several years of dedicated study to develop an understanding of and the haptic feel for catheter navigation and interventional treatments. However, medicolegal concerns and work hour restrictions may limit the experience trainees receive. Simulators allow trainees to improve their technical expertise and also allow physicians and industry to collaborate in the development of innovative devices. 3The ideal training model should be inexpensive, readily available, and have haptic characteristics similar to those encountered in the endovascular treatment of human disorders. Animal and computer-based models have been developed for this purpose. 3,5,7 While each model has certain advantages and disadvantages, it is difficult to reproduce all the haptic qualities necessary for these procedures using virtual simulators or animal models.4,6-8 Thus, it is necessary to continue to develop and research new techniques for neurointerventional training. In this article, we abbreviatioNs GDC = Guglielmi detachable coil; HP = human placenta. obJective The development of neurointerventional treatments of central nervous system disorders has resulted in the need for adequate training environments for novice interventionalists. Virtual simulators offer anatomical definition but lack adequate tactile feedback. Animal models, which provide more lifelike training, require an appropriate infrastructure base. The authors describe a training model for neurointerventional procedures using the human placenta (HP), which affords haptic training with significantly fewer resource requirements, and discuss its validation. methods Twelve HPs were prepared for simulated endovascular procedures. Training exercises performed by interventional neuroradiologists and novice fellows were placental angiography, stent placement, aneurysm coiling, and intravascular liquid embolic agent injection. results The endovascular training exercises proposed can be easily reproduced in the HP. Face, content, and construct validity were assessed by 6 neurointerventional radiologists and 6 novice fellows in interventional radiology. coNclusioNs The use of HP provides an inexpensive training model for the training of neurointerventionalists. Preliminary validation results show that this simulation model has face and content validity and has demonstrated construct validity for the interventions assessed in this study.