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This chronic inflammation may be opposed by endogenous mechanisms to limit inflammation, for example, by the actions of annexin A1 (ANXA1), an endogenous glucocorticoid\u2010regulated protein that has anti\u2010inflammatory and pro\u2010resolving activity. We hypothesized the pro\u2010resolving mediator ANXA1 protects against age\u2010induced changes in blood pressure (BP), cardiovascular structure and function, and cardiac senescence. BP was measured monthly in conscious mature (4\u2010month) and middle\u2010aged (12\u2010month) ANXA1\u2010deficient (ANXA1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) and wild\u2010type C57BL\/6 mice. Body composition was measured using EchoMRI, and both cardiac and vascular function using ultrasound imaging. Cardiac hypertrophy, fibrosis and senescence, vascular fibrosis, elastin, and calcification were assessed histologically. Gene expression relevant to structural remodeling, inflammation, and cardiomyocyte senescence were also quantified. In C57BL\/6 mice, progression from 4 to 12\u2009months of age did not affect the majority of cardiovascular parameters measured, with the exception of mild cardiac hypertrophy, vascular calcium, and collagen deposition. Interestingly, ANXA1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice exhibited higher BP, regardless of age. Additionally, age progression had a marked impact in ANXA1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, with markedly augmented vascular remodeling, impaired vascular distensibility, and body composition. Consistent with vascular dysfunction, cardiac dysfunction, and hypertrophy were also evident, together with markers of senescence and inflammation. These findings suggest that endogenous ANXA1 plays a critical role in regulating BP, cardiovascular function, and remodeling and delays cardiac senescence. Our findings support the development of novel ANXA1\u2010based therapies to prevent age\u2010related cardiovascular pathologies.\n                  <\/jats:p>","DOI":"10.1096\/fj.202301802r","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T04:01:29Z","timestamp":1707278489000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The\n                    <scp>pro\u2010resolving<\/scp>\n                    mediator, annexin\n                    <scp>A1<\/scp>\n                    regulates blood pressure, and\n                    <scp>age\u2010associated<\/scp>\n                    changes in cardiovascular function and remodeling"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3999-7591","authenticated-orcid":false,"given":"Jaideep","family":"Singh","sequence":"first","affiliation":[{"name":"Drug Discovery Biology Monash Institute of Pharmaceutical Sciences, Monash University  Parkville Victoria Australia"},{"name":"Baker Heart &amp; 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