PT -期刊文章盟桑多瓦尔胡里奥AU -德尔Valle-Mondragón, Leonardo AU - Masso, Felipe AU - Zayas, Nayeli AU - Pulido, Tomás AU - Teijeiro, Ricardo AU - Gonzalez-Pacheco, Hector AU - Olmedo-Ocampo, Rossana AU - Sisniega, Carlos AU - Paez-Arenas, Araceli AU - Pastelin-Hernandez, Gustavo AU - Gomez-Arroyo, Jose AU - Voelkel, Norbert F. TI - Angiotensin converting enzyme 2 and angiotensin (1–7) axis in pulmonary arterial hypertension AID - 10.1183/13993003.02416-2019 DP - 2020 Jul 01 TA - European Respiratory Journal PG - 1902416 VI - 56 IP - 1 4099 - //www.qdcxjkg.com/content/56/1/1902416.short 4100 - //www.qdcxjkg.com/content/56/1/1902416.full SO - Eur Respir J2020 Jul 01; 56 AB - Background In animal models of pulmonary arterial hypertension (PAH), angiotensin-converting enzyme (ACE)2 and angiotensin (Ang)-(1–7) have been shown to have vasodilatory, antiproliferative, antifibrotic and antihypertrophic properties. However, the status and role of the ACE2-Ang(1–7) axis in human PAH is incompletely understood.Methods We studied 85 patients with a diagnosis of PAH of distinct aetiologies. 55 healthy blood donors paired for age and sex served as controls. Blood samples were obtained from the pulmonary artery in patients with PAH during right heart catheterisation. Peripheral blood was obtained for both groups. Ang(1–7) and -II were measured using zone capillary electrophoresis. Aldosterone, Ang(1–9), AngA and ACE2 were measured using ELISA, and ACE2 activity was determined enzymatically.Results Of the 85 patients, 47 had idiopathic PAH, 25 had PAH associated with congenital heart disease and 13 had PAH associated with collagen vascular disease. Compared to controls, patients with PAH had a higher concentration of AngII (median 1.03, interquartile range 0.72–1.88 pmol·mL−1 versus 0.19, 0.10–0.37 pmol·mL−1; p<0.001) and of aldosterone (88.7, 58.7–132 ng·dL−1 versus 12.9, 9.55–19.9 ng·dL−1; p<0.001). Conversely, PAH patients had a lower concentration of Ang(1–7) than controls (0.69, 0.474–0.91 pmol·mL−1 versus 4.07, 2.82–6.73 pmol·mL−1; p<0.001), and a lower concentration of Ang(1–9) and AngA. Similarly, the ACE2 concentration was higher than in controls (8.7, 5.35–13.2 ng·mL−1 versus 4.53, 1.47–14.3 ng·mL−1; p=0.011), whereas the ACE2 activity was significantly reduced (1.88, 1.08–2.81 nmol·mL−1 versus 5.97, 3.1–17.8 nmol·mL−1; p<0.001). No significant differences were found among the three different aetiological forms of PAH.Conclusions The AngII–ACE2–Ang(1–7) axis appears to be altered in human PAH and we propose that this imbalance, in favour of AngII, plays a role in the pathogenesis of the severe PAH. Further mechanistic studies are warranted.This study demonstrates that in patients with PAH of different aetiologies there are alterations of the ACE2-angiotensin (1–7)-MAS axis. Analysis of blood samples also demonstrates the presence of antibodies directed against ACE2 https://bit.ly/3alEbnJ