{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T21:03:10Z","timestamp":1785790990872,"version":"3.56.0"},"reference-count":70,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["HL075360"],"award-info":[{"award-number":["HL075360"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Veterans Administration","award":["BX000505"],"award-info":[{"award-number":["BX000505"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2018,2,1]]},"abstract":"<jats:p>Matrix metalloproteinase (MMP)-9 increases in the myocardium with advanced age and after myocardial infarction (MI). Because young transgenic (TG) mice overexpressing human MMP-9 only in macrophages show better outcomes post-MI, whereas aged TG mice show a worse aging phenotype, we wanted to evaluate the effect of aging superimposed on MI to see if the detrimental effect of aging counteracted the benefits of macrophage MMP-9 overexpression. We used 17- to 28-mo-old male and female C57BL\/6J wild-type (WT) and TG mice ( n = 10\u201321 mice\/group) to evaluate the effects of aging superimposed on MI. Despite similar infarct areas and mortality rates at day 7 post-MI, aging TG mice showed improved diastolic properties and remodeling index compared with WT mice (both P &lt; 0.05). Macrophage numbers were higher in TG than WT mice at days 0 and 7 post-MI, and the post-MI increase was due to elevated cluster of differentiation 18 protein levels (all P &lt; 0.05). RNA sequencing analysis of cardiac macrophages isolated from day 7 post-MI infarcts identified 1,276 statistically different (all P &lt; 0.05) genes (994 increased and 282 decreased in TG mice). Reduced expression of vascular endothelial growth factor A, platelet-derived growth factor subunit A, and transforming growth factor-\u03b2<jats:sub>3<\/jats:sub>, along with elevated expression of tissue inhibitor of MMP-4, in macrophages revealed mechanisms of indirect downstream effects on fibroblasts and neovascularization. While collagen accumulation was enhanced in TG mice compared with WT mice at days 0 and 7 post-MI ( P &lt; 0.05 for both), the post-MI collagen cross-linking ratio was higher in WT mice ( P &lt; 0.05), consistent with increased diastolic volumes. Vessel numbers [by Griffonia ( Bandeiraea) simplicifolia lectin I staining] were decreased in TG mice compared with WT mice at days 0 and 7 post-MI ( P &lt; 0.05 for both). In conclusion, macrophage-derived MMP-9 improved post-MI cardiac wound healing through direct and indirect mechanisms to improve diastolic physiology and remodeling.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY Aging mice with macrophage overexpression of matrix metalloproteinase-9 have increased macrophage numbers 7 days after myocardial infarction, resulting in improved diastolic physiology and left ventricular remodeling through effects on cardiac wound healing.<\/jats:p>","DOI":"10.1152\/ajpheart.00453.2017","type":"journal-article","created":{"date-parts":[[2017,10,14]],"date-time":"2017-10-14T01:10:33Z","timestamp":1507943433000},"page":"H224-H235","source":"Crossref","is-referenced-by-count":44,"title":["Macrophage overexpression of matrix metalloproteinase-9 in aged mice improves diastolic physiology and cardiac wound healing after myocardial infarction"],"prefix":"10.1152","volume":"314","author":[{"given":"Cesar A.","family":"Meschiari","sequence":"first","affiliation":[{"name":"Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Jung","sequence":"additional","affiliation":[{"name":"Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rugmani Padmanabhan","family":"Iyer","sequence":"additional","affiliation":[{"name":"Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriy","family":"Yabluchanskiy","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroe","family":"Toba","sequence":"additional","affiliation":[{"name":"Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi"},{"name":"Division of Pathological Sciences, Department of Clinical Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Garrett","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4090-0391","authenticated-orcid":false,"given":"Merry L.","family":"Lindsey","sequence":"additional","affiliation":[{"name":"Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi"},{"name":"G. 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