{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:31:11Z","timestamp":1792042271622,"version":"4.4.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              Ang-(1-7) (angiotensin (1-7)) via MasR (Mas receptor) opposes vaso-injurious actions of Ang II (angiotensin II) as shown in models of pulmonary hypertension. The underlying mechanisms remain unclear. We hypothesized cross talk between Ang-(1-7) and the protective arm of the ET-1 (endothelin-1) system involving MasR and ET\n              <jats:sub>B<\/jats:sub>\n              R (endothelin receptor type B).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>To address this, we studied multiple models: in vivo, in a mouse model of ET-1\u2013associated vascular injury (hypoxia-induced pulmonary hypertension); ex vivo, in isolated mouse arteries; and in vitro, in human endothelial cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Pulmonary hypertension mice exhibited pulmonary vascular remodeling, endothelial dysfunction, and ET-1\u2013induced hypercontractility. Ang-(1-7) treatment (14 days) ameliorated these effects and increased the expression of vascular ET\n              <jats:sub>B<\/jats:sub>\n              R. In human endothelial cells, Ang-(1-7)\u2013induced activation of eNOS (endothelial NO synthase)\/NO was attenuated by A779 (MasR antagonist) and BQ788 (ET\n              <jats:sub>B<\/jats:sub>\n              R antagonist). A779 inhibited ET-1\u2013induced signaling. Coimmunoprecipitation and peptide array experiments demonstrated the interaction between MasR and ET\n              <jats:sub>B<\/jats:sub>\n              R. Binding sites for ET\n              <jats:sub>B<\/jats:sub>\n              R were mapped to MasR (amino acids 290\u2013314). Binding sites for MasR on ET\n              <jats:sub>B<\/jats:sub>\n              R were identified (amino acids 176\u2013200). Peptides that disrupt MasR:ET\n              <jats:sub>B<\/jats:sub>\n              R prevented Ang-(1-7) and ET-1 signaling. Using high-throughput screening, we identified compounds that enhance MasR:ET\n              <jats:sub>B<\/jats:sub>\n              R interaction, which we termed enhancers. Enhancers increased Ang-(1-7)\u2013induced eNOS activity, NO production, and Ang-(1-7)\u2013mediated vasorelaxation, and reduced contractile responses.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              We identify cross talk between Ang-(1-7) and ET-1 through MasR:ET\n              <jats:sub>B<\/jats:sub>\n              R interaction as a novel network that is vasoprotective. Promoting coactivity between these systems amplifies Ang-(1-7) signaling, increases ET-1\/ET\n              <jats:sub>B<\/jats:sub>\n              R-mediated vascular actions, and attenuates the injurious effects of ET-1. Enhancing Ang-(1-7)\/MasR:ET-1\/ET\n              <jats:sub>B<\/jats:sub>\n              R signaling may have therapeutic potential in conditions associated with vascular damage.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/hypertensionaha.124.22693","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T10:00:44Z","timestamp":1733392844000},"page":"267-281","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Ang-(1-7) and ET-1 Interplay Through Mas and ET\n            <sub>B<\/sub>\n            Receptor Interaction Defines a Novel Vasoprotective Mechanism"],"prefix":"10.1161","volume":"82","author":[{"given":"Augusto C.","family":"Montezano","sequence":"first","affiliation":[{"name":"Research Institute of McGill University Health Centre, Montreal, Quebec, Canada (A.C.M., L.L.C., Y.N., S.A.L., 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