Angiotensin-converting enzyme inhibitor treatment early after myocardial infarction attenuates acute cardiac and neuroinflammation without effect on chronic neuroinflammation
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| Název: | Angiotensin-converting enzyme inhibitor treatment early after myocardial infarction attenuates acute cardiac and neuroinflammation without effect on chronic neuroinflammation |
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| Autoři: | Tobias Borchert, Annika Hess, Mario Lukačević, Tobias L. Ross, Frank M. Bengel, James T. Thackeray |
| Zdroj: | Eur J Nucl Med Mol Imaging |
| Informace o vydavateli: | Springer Science and Business Media LLC, 2020. |
| Rok vydání: | 2020 |
| Témata: | Inflammation, 0301 basic medicine, Myocardial Infarction, Angiotensin-Converting Enzyme Inhibitors, Heart, 3. Good health, Mice, Inbred C57BL, Mice, 03 medical and health sciences, 0302 clinical medicine, Enalapril, Positron emission tomography, Enalapril/pharmacology [MeSH], Mice, Inbred C57BL [MeSH], Heart/diagnostic imaging [MeSH], Neuroinflammation, TSPO, Nervous System Diseases/drug therapy [MeSH], Enalapril/therapeutic use [MeSH], Myocardial Infarction/drug therapy [MeSH], Animals [MeSH], Heart/drug effects [MeSH], Angiotensin-Converting Enzyme Inhibitors/therapeutic use [MeSH], Nervous System Diseases/diagnostic imaging [MeSH], Original Article, Acute Disease [MeSH], Mice [MeSH], Inflammation/diagnostic imaging [MeSH], Myocardial Infarction/complications [MeSH], Myocardial Infarction/diagnostic imaging [MeSH], Inflammation/drug therapy [MeSH], Preclinical Imaging, Chronic Disease [MeSH], Myocardial infarction, Acute Disease, Chronic Disease, Animals, Nervous System Diseases |
| Popis: | Purpose Myocardial infarction (MI) triggers a local inflammatory response which orchestrates cardiac repair and contributes to concurrent neuroinflammation. 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. Methods C57BL/6 mice underwent permanent coronary artery ligation (n = 41) or sham surgery (n = 9). Subgroups received ACE inhibitor enalapril (20 mg/kg, oral) either early (anti-inflammatory strategy; 10 days treatment beginning 3 days prior to surgery; n = 9) or delayed (anti-remodeling; continuous from 7 days post-MI; n = 16), or no therapy (n = 16). Cardiac and neuroinflammation were serially investigated using whole-body macrophage- and microglia-targeted translocator protein (TSPO) PET at 3 days, 7 days, and 8 weeks. In vivo PET signal was validated by autoradiography and histopathology. Results Myocardial infarction evoked higher TSPO signal in the infarct region at 3 days and 7 days compared with sham (p p = 0.005). At 8 weeks 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% (p p = 0.045), respectively. The acute infarct signal predicted late functional outcome (r = 0.418, p = 0.038). 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 weeks after MI (p = 0.090) without an effect on chronic neuroinflammation. Conclusions 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. |
| Druh dokumentu: | Article Other literature type |
| Jazyk: | English |
| ISSN: | 1619-7089 1619-7070 |
| DOI: | 10.1007/s00259-020-04736-8 |
| Přístupová URL adresa: | https://link.springer.com/content/pdf/10.1007/s00259-020-04736-8.pdf https://pubmed.ncbi.nlm.nih.gov/32125488 https://link.springer.com/article/10.1007/s00259-020-04736-8 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248052 https://paperity.org/p/233389096/angiotensin-converting-enzyme-inhibitor-treatment-early-after-myocardial-infarction https://link.springer.com/content/pdf/10.1007%2Fs00259-020-04736-8.pdf https://repository.publisso.de/resource/frl:6470232 |
| Rights: | CC BY |
| Přístupové číslo: | edsair.doi.dedup.....de890bc165ad9a3f4fe5da09d2d08375 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Purpose Myocardial infarction (MI) triggers a local inflammatory response which orchestrates cardiac repair and contributes to concurrent neuroinflammation. 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. Methods C57BL/6 mice underwent permanent coronary artery ligation (n = 41) or sham surgery (n = 9). Subgroups received ACE inhibitor enalapril (20 mg/kg, oral) either early (anti-inflammatory strategy; 10 days treatment beginning 3 days prior to surgery; n = 9) or delayed (anti-remodeling; continuous from 7 days post-MI; n = 16), or no therapy (n = 16). Cardiac and neuroinflammation were serially investigated using whole-body macrophage- and microglia-targeted translocator protein (TSPO) PET at 3 days, 7 days, and 8 weeks. In vivo PET signal was validated by autoradiography and histopathology. Results Myocardial infarction evoked higher TSPO signal in the infarct region at 3 days and 7 days compared with sham (p p = 0.005). At 8 weeks 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% (p p = 0.045), respectively. The acute infarct signal predicted late functional outcome (r = 0.418, p = 0.038). 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 weeks after MI (p = 0.090) without an effect on chronic neuroinflammation. Conclusions 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. |
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| ISSN: | 16197089 16197070 |
| DOI: | 10.1007/s00259-020-04736-8 |