{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:49:17Z","timestamp":1788587357572,"version":"build-2803163510"},"reference-count":74,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T00:00:00Z","timestamp":1717632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this study, we investigated whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein may modify angiotensin-converting enzyme 2 (ACE2) activity in the plasma, heart, kidney, liver, lung, and six brain regions (amygdala, brain stem, cortex, hippocampus, hypothalamus, and striatum) of diabetic and hypertensive rats. We determine ACE2 activity in the plasma and lysates of heart, kidney, liver, lung, and six brain regions. MLN-4760 inhibits ACE2 activity in the plasma and all organs. On the other hand, soluble ACE2 (sACE2) activity increased in the plasma of diabetic rats, and there was no change in the plasma of hypertensive rats. ACE2 activity was augmented in the liver, brain stem, and striatum, while it decreased in the kidney, amygdala, cortex, and hippocampus of diabetic rats. ACE2 activity increased in the kidney, liver, and lung, while it decreased in the heart, amygdala, cortex, and hypothalamus of hypertensive rats. We measured the ACE2 content via enzyme-linked immunosorbent assay and found that ACE2 protein levels increased in the heart, while it decreased in the plasma, kidney, brain stem, cortex, hippocampus, hypothalamus, and striatum of diabetic rats. ACE2 protein levels decreased in the brain stem, cortex, hippocampus, and hypothalamus of hypertensive rats. Our data showed that the spike protein enhanced ACE2 activity in the liver and lungs of diabetic rats, as well as in the heart and three of the brain regions (cortex, hypothalamus, and striatum) of hypertensive rats.<\/jats:p>","DOI":"10.3390\/ijms25116276","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T12:04:28Z","timestamp":1717675468000},"page":"6276","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["SARS-CoV-2 Spike Protein Enhances Carboxypeptidase Activity of Angiotensin-Converting Enzyme 2"],"prefix":"10.3390","volume":"25","author":[{"given":"X\u00f3chitl Andrea","family":"Mendiola-Salazar","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Instituto Nacional de Cardiolog\u00eda \u201cIgnacio Ch\u00e1vez\u201d, Mexico City 14080, Mexico"},{"name":"Carrera de M\u00e9dico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 54090, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie A.","family":"Mungu\u00eda-Laguna","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Instituto Nacional de Cardiolog\u00eda \u201cIgnacio Ch\u00e1vez\u201d, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4073-524X","authenticated-orcid":false,"given":"Martha","family":"Franco","sequence":"additional","affiliation":[{"name":"Department of Cardio-Renal Pathophysiology, Instituto Nacional de Cardiolog\u00eda \u201cIgnacio Ch\u00e1vez\u201d, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6703-2176","authenticated-orcid":false,"given":"Agustina","family":"Cano-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Physiology, Instituto Nacional de Cardiolog\u00eda \u201cIgnacio Ch\u00e1vez\u201d, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Santamar\u00eda Sosa","sequence":"additional","affiliation":[{"name":"Department of Cardio-Renal Pathophysiology, Instituto Nacional de Cardiolog\u00eda \u201cIgnacio Ch\u00e1vez\u201d, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0265-668X","authenticated-orcid":false,"given":"Roc\u00edo","family":"Bautista-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Instituto Nacional de Cardiolog\u00eda \u201cIgnacio Ch\u00e1vez\u201d, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e012581","DOI":"10.1136\/bmjgh-2023-012581","article-title":"Associations of diabetes, hypertension and obesity with COVID-19 mortality: A systematic review and meta-analysis","volume":"8","author":"Li","year":"2023","journal-title":"BMJ Glob. 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