{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:41:16Z","timestamp":1774071676761,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01EO1503"],"award-info":[{"award-number":["01EO1503"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008454","name":"Boehringer Ingelheim Stiftung","doi-asserted-by":"publisher","award":["Experimental Vascular Biology Mainz"],"award-info":[{"award-number":["Experimental Vascular Biology Mainz"]}],"id":[{"id":"10.13039\/501100008454","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Aims: Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a cornerstone of drug therapy after myocardial infarction (MI) and improve left ventricular function and survival. We aimed to elucidate the impact of early treatment with the ACE inhibitor ramipril on the hematopoietic response after MI, as well as on the chronic systemic and vascular inflammation. Methods and Results: In a mouse model of MI, induced by permanent ligation of the left anterior descending artery, immediate initiation of treatment with ramipril (10 mg\/k\/d via drinking water) reduced cardiac inflammation and the number of circulating inflammatory monocytes, whereas left ventricular function was not altered significantly, respectively. This effect was accompanied by enhanced retention of hematopoietic stem cells, Lin\u2212Sca1\u2212c-Kit+CD34+CD16\/32+ granulocyte\u2013macrophage progenitors (GMP) and Lin\u2212Sca1\u2212c-Kit+CD150\u2212CD48\u2212 multipotent progenitors (MPP) in the bone marrow, with an upregulation of the niche factors Angiopoetin 1 and Kitl at 7 d post MI. Long-term ACE inhibition for 28 d limited vascular inflammation, particularly the infiltration of Ly6Chigh monocytes\/macrophages, and reduced superoxide formation, resulting in improved endothelial function in mice with ischemic heart failure. Conclusion: ACE inhibition modulates the myeloid inflammatory response after MI due to the retention of myeloid precursor cells in their bone marrow reservoir. This results in a reduction in cardiac and vascular inflammation with improvement in survival after MI.<\/jats:p>","DOI":"10.3390\/antiox10030396","type":"journal-article","created":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T20:20:43Z","timestamp":1615148443000},"page":"396","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["ACE Inhibition Modulates Myeloid Hematopoiesis after Acute Myocardial Infarction and Reduces Cardiac and Vascular Inflammation in Ischemic Heart Failure"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1992-3967","authenticated-orcid":false,"given":"Wolf-Stephan","family":"Rudi","sequence":"first","affiliation":[{"name":"Center for Thrombosis and Haemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"},{"name":"Center for Cardiology-Cardiology I, University Medical Center Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"},{"name":"German Center for Cardiovascular Research (DZHK, Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung), Partner Site Rhine-Main, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Molitor","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Haemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"},{"name":"Center for Cardiology-Cardiology I, University Medical Center Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"},{"name":"German Center for Cardiovascular Research (DZHK, Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung), Partner Site Rhine-Main, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkata","family":"Garlapati","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Haemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"},{"name":"German Center for Cardiovascular Research (DZHK, Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung), Partner Site Rhine-Main, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Finger","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Haemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1446-8101","authenticated-orcid":false,"given":"Johannes","family":"Wild","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Haemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"},{"name":"Center for Cardiology-Cardiology I, University Medical Center Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"},{"name":"German Center for Cardiovascular Research (DZHK, Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung), Partner Site Rhine-Main, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5503-4150","authenticated-orcid":false,"given":"Thomas","family":"M\u00fcnzel","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Haemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"},{"name":"Center for Cardiology-Cardiology I, University Medical Center Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"},{"name":"German Center for Cardiovascular Research (DZHK, Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung), Partner Site Rhine-Main, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4462-3747","authenticated-orcid":false,"given":"Susanne H.","family":"Karbach","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Haemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"},{"name":"Center for Cardiology-Cardiology I, University Medical Center Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"},{"name":"German Center for Cardiovascular Research (DZHK, Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung), Partner Site Rhine-Main, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-2781","authenticated-orcid":false,"given":"Philip","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Haemostasis, University Medical Center Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"},{"name":"Center for Cardiology-Cardiology I, University Medical Center Mainz, Langenbeckstra\u00dfe 1, 55131 Mainz, Germany"},{"name":"German Center for Cardiovascular Research (DZHK, Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung), Partner Site Rhine-Main, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"ref_1","first-page":"1167","article-title":"2016 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure","volume":"69","author":"Ponikowski","year":"2016","journal-title":"Rev. Espa\u00f1ola Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1161\/CIRCRESAHA.120.315895","article-title":"Hematopoiesis and Cardiovascular Disease","volume":"126","author":"Poller","year":"2020","journal-title":"Circ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.stem.2015.04.008","article-title":"Myocardial Infarction Activates CCR2(+) Hematopoietic Stem and Progenitor Cells","volume":"16","author":"Dutta","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.regpep.2006.01.007","article-title":"Angiotensin II type 1 receptor expression on human leukocyte subsets: A flow cytometric and RT-PCR study","volume":"134","author":"Rasini","year":"2006","journal-title":"Regul. Pept."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1056\/NEJM199704103361506","article-title":"Nuclear factor-kappaB: A pivotal transcription factor in chronic inflammatory diseases","volume":"336","author":"Barnes","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1161\/01.CIR.100.15.1646","article-title":"Angiotensin II stimulates intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells and increases soluble ICAM-1 release in vivo","volume":"100","author":"Pastore","year":"1999","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1161\/01.CIR.100.11.1223","article-title":"Angiotensin II induces vascular cell adhesion molecule-1 expression in rat vasculature: A potential link between the renin-angiotensin system and atherosclerosis","volume":"100","author":"Tummala","year":"1999","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S1357-2725(02)00271-6","article-title":"Inflammation and angiotensin II","volume":"35","author":"Suzuki","year":"2003","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1093\/cvr\/cvaa042","article-title":"Nox2+ Myeloid cells drive vascular inflammation and endothelial dysfunction in heart failure after myocardial infarction via angiotensin II receptor type 1","volume":"117","author":"Molitor","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1161\/HYPERTENSIONAHA.115.06474","article-title":"Angiotensin II Regulation of Proliferation, Differentiation, and Engraftment of Hematopoietic Stem Cells","volume":"67","author":"Kim","year":"2016","journal-title":"Hypertension"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1126\/science.1175202","article-title":"Identification of splenic reservoir monocytes and their deployment to inflammatory sites","volume":"325","author":"Swirski","year":"2009","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1093\/cvr\/cvz092","article-title":"A sequential interferon gamma directed chemotactic cellular immune response determines survival and cardiac function post myocardial infarction","volume":"115","author":"Finger","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"H1187","DOI":"10.1152\/ajpheart.00895.2006","article-title":"Validation of the wall motion score and myocardial performance indexes as novel techniques to assess cardiac function in mice after myocardial infarction","volume":"292","author":"Zhang","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/nm.3647","article-title":"Hematopoietic stem cell niche maintenance during homeostasis and regeneration","volume":"20","author":"Mendelson","year":"2014","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nature12984","article-title":"The bone marrow niche for haematopoietic stem cells","volume":"505","author":"Morrison","year":"2014","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.mce.2008.11.003","article-title":"NADPH oxidases and angiotensin II receptor signaling","volume":"302","author":"Garrido","year":"2009","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E58","DOI":"10.1161\/01.RES.0000012569.55432.02","article-title":"Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide\/cGMP signaling","volume":"90","author":"Mollnau","year":"2002","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Frangogiannis, N.G. (2015). Interleukin-1 in cardiac injury, repair, and remodeling: Pathophysiologic and translational concepts. Discoveries, 3.","DOI":"10.15190\/d.2015.33"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1097\/HCO.0000000000000158","article-title":"Inflammation in cardiac injury, repair and regeneration","volume":"30","author":"Frangogiannis","year":"2015","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nrcardio.2014.28","article-title":"The inflammatory response in myocardial injury, repair, and remodelling","volume":"11","author":"Frangogiannis","year":"2014","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/nyas.12393","article-title":"The journey from stem cell to macrophage","volume":"1319","author":"Pittet","year":"2014","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nature11260","article-title":"Myocardial infarction accelerates atherosclerosis","volume":"487","author":"Dutta","year":"2012","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.jacc.2019.12.056","article-title":"Diminished Reactive Hematopoiesis and Cardiac Inflammation in a Mouse Model of Recurrent Myocardial Infarction","volume":"75","author":"Cremer","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41580-019-0103-9","article-title":"Haematopoietic stem cell activity and interactions with the niche","volume":"20","author":"Pinho","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1161\/CIRCRESAHA.110.227454","article-title":"Angiotensin-converting enzyme inhibition prevents the release of monocytes from their splenic reservoir in mice with myocardial infarction","volume":"107","author":"Leuschner","year":"2010","journal-title":"Circ. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1084\/jem.20141642","article-title":"Macrophages retain hematopoietic stem cells in the spleen via VCAM-1","volume":"212","author":"Dutta","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.jacc.2015.06.027","article-title":"Apixaban Plus Mono Versus Dual Antiplatelet Therapy in Acute Coronary Syndromes: Insights From the APPRAISE-2 Trial","volume":"66","author":"Hess","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1056\/NEJMe1112770","article-title":"A new era in secondary prevention after acute coronary syndrome","volume":"366","author":"Roe","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1016\/j.jacc.2013.01.066","article-title":"Rivaroxaban in patients stabilized after a ST-segment elevation myocardial infarction: Results from the ATLAS ACS-2-TIMI-51 trial (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction-51)","volume":"61","author":"Mega","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0002-8703(02)94777-0","article-title":"Beneficial effects of angiotensin-converting enzyme inhibitor and nitrate association on left ventricular remodeling in patients with large acute myocardial infarction: The Delapril Remodeling after Acute Myocardial Infarction (DRAMI) trial","volume":"146","author":"Latini","year":"2003","journal-title":"Am. Heart J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/S0735-1097(00)00638-0","article-title":"Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: Systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting Enzyme Inhibitor Myocardial Infarction Collaborative Group","volume":"35","author":"Latini","year":"2000","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1056\/NEJM199209033271001","article-title":"Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators","volume":"327","author":"Pfeffer","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.cardfail.2010.04.002","article-title":"Effects of ACE2 inhibition in the post-myocardial infarction heart","volume":"16","author":"Kim","year":"2010","journal-title":"J. Card. Fail."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1161\/CIRCRESAHA.111.243162","article-title":"Regulation of the inflammatory response in cardiac repair","volume":"110","author":"Frangogiannis","year":"2012","journal-title":"Circ. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(17)32814-3","article-title":"Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: A secondary analysis from the CANTOS randomised controlled trial","volume":"391","author":"Ridker","year":"2018","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1161\/CIRCRESAHA.116.309001","article-title":"Proliferation and Recruitment Contribute to Myocardial Macrophage Expansion in Chronic Heart Failure","volume":"119","author":"Sager","year":"2016","journal-title":"Circ. Res."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/3\/396\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:33:50Z","timestamp":1760160830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/3\/396"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,5]]},"references-count":37,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["antiox10030396"],"URL":"https:\/\/doi.org\/10.3390\/antiox10030396","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,5]]}}}