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Angiotensin-converting enzyme (ACE) inhibitor therapy not only attenuates cardiac remodeling by interfering with the neurohumoral system, but also influences acute leukocyte mobilization from hematopoietic reservoirs. Here, we seek to dissect the anti-inflammatory and anti-remodeling contributions of ACE inhibitors to the benefit of heart and brain outcomes after MI.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>C57BL\/6 mice underwent permanent coronary artery ligation (<jats:italic>n<\/jats:italic>\u2009=\u200941) or sham surgery (<jats:italic>n<\/jats:italic>\u2009=\u20099). Subgroups received ACE inhibitor enalapril (20\u00a0mg\/kg, oral) either early (anti-inflammatory strategy; 10 days treatment beginning 3 days prior to surgery; <jats:italic>n<\/jats:italic>\u2009=\u20099) or delayed (anti-remodeling; continuous from 7\u00a0days post-MI; <jats:italic>n<\/jats:italic>\u2009=\u200916), or no therapy (<jats:italic>n<\/jats:italic>\u2009=\u200916). Cardiac and neuroinflammation were serially investigated using whole-body macrophage- and microglia-targeted translocator protein (TSPO) PET at 3\u00a0days, 7\u00a0days, and 8\u00a0weeks. In vivo PET signal was validated by autoradiography and histopathology.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Myocardial infarction evoked higher TSPO signal in the infarct region at 3\u00a0days and 7\u00a0days compared with sham (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), with concurrent elevation in brain TSPO signal (+\u200918%, <jats:italic>p<\/jats:italic>\u2009=\u20090.005). At 8\u00a0weeks after MI, remote myocardium TSPO signal was increased, consistent with mitochondrial stress, and corresponding to recurrent neuroinflammation. Early enalapril treatment lowered the acute TSPO signal in the heart and brain by 55% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and 14% (<jats:italic>p<\/jats:italic>\u2009=\u20090.045), respectively. The acute infarct signal predicted late functional outcome (<jats:italic>r<\/jats:italic>\u2009=\u20090.418, <jats:italic>p<\/jats:italic>\u2009=\u20090.038). Delayed enalapril treatment reduced chronic myocardial TSPO signal, consistent with alleviated mitochondrial stress. Early enalapril therapy tended to lower TSPO signal in the failing myocardium at 8\u00a0weeks after MI (<jats:italic>p<\/jats:italic>\u2009=\u20090.090) without an effect on chronic neuroinflammation.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Whole-body TSPO PET identifies myocardial macrophage infiltration and neuroinflammation after MI, and altered cardiomyocyte mitochondrial density in chronic heart failure. Improved chronic cardiac outcome by enalapril treatment derives partially from acute anti-inflammatory activity with complementary benefits in later stages. Whereas early ACE inhibitor therapy lowers acute neuroinflammation, chronic alleviation is not achieved by early or delayed ACE inhibitor therapy, suggesting a more complex mechanism underlying recurrent neuroinflammation in ischemic heart failure.<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s00259-020-04736-8","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T09:03:58Z","timestamp":1583226238000},"page":"1757-1768","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Angiotensin-converting enzyme inhibitor treatment early after myocardial infarction attenuates acute cardiac and neuroinflammation without effect on chronic neuroinflammation"],"prefix":"10.1007","volume":"47","author":[{"given":"Tobias","family":"Borchert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Hess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Luka\u010devi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias L.","family":"Ross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank M.","family":"Bengel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9031-100X","authenticated-orcid":false,"given":"James T.","family":"Thackeray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,3]]},"reference":[{"key":"4736_CR1","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1093\/eurheartj\/ehx628","volume":"39","author":"A Timmis","year":"2018","unstructured":"Timmis A, Townsend N, Gale C, Grobbee R, Maniadakis N, Flather M, et al. 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