Myocardial Inflammation Predicts Remodeling and Neuroinflammation After Myocardial Infarction

The local inflammatory tissue response after acute myocardial infarction (MI) determines subsequent healing. Systemic interaction may induce neuroinflammation as a precursor to neurodegeneration. This study sought to assess the influence of MI on cardiac and brain inflammation using noninvasive posi...

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Bibliographic Details
Published in:Journal of the American College of Cardiology 2018-01, Vol.71 (3), p.263-275
Main Authors: Thackeray, James T., Hupe, Henri C., Wang, Yong, Bankstahl, Jens P., Berding, Georg, Ross, Tobias L., Bauersachs, Johann, Wollert, Kai C., Bengel, Frank M.
Format: Article
Language:English
Subjects:
Angiotensin-converting enzyme inhibitors
Animal cognition
Animals
Brain
Brain - diagnostic imaging
Brain - immunology
Cardiology
Cardiomyocytes
Cardiovascular disease
Cognitive ability
Coronary artery
Coronary artery disease
Coronary vessels
Cytokines
Dementia
Dosage
Enzyme inhibitors
Forecasting
Heart
Heart attacks
Heart diseases
Heart failure
Hypertension
Immune response
Infiltration
Inflammation
Inflammation - diagnostic imaging
Inflammation - physiopathology
Macrophages
Medical imaging
Mice
Mice, Inbred C57BL
Microglia
Mitochondria
Molecular Imaging - methods
Myocardial infarction
Myocardial Infarction - diagnostic imaging
Myocardial Infarction - immunology
Myocardium - immunology
Myocardium - pathology
Neurodegeneration
Neuroimaging
Neurology
Ostomy
Patients
Peptidyl-dipeptidase A
Positron emission
Positron emission tomography
Proteins
Surgery
Territory
Tomography
Ventricle
Ventricular Remodeling - physiology
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Summary:The local inflammatory tissue response after acute myocardial infarction (MI) determines subsequent healing. Systemic interaction may induce neuroinflammation as a precursor to neurodegeneration. This study sought to assess the influence of MI on cardiac and brain inflammation using noninvasive positron emission tomography (PET) of the heart-brain axis. After coronary artery ligation or sham surgery, mice (n = 49) underwent serial whole-body PET imaging of the mitochondrial translocator protein (TSPO) as a marker of activated macrophages and microglia. Patients after acute MI (n = 3) were also compared to healthy controls (n = 9). Infarct mice exhibited elevated myocardial TSPO signal at 1 week versus sham (percent injected dose per gram: 8.0 ± 1.6 vs. 4.8 ± 0.9; p < 0.001), localized to activated CD68+ inflammatory cells in the infarct. Early TSPO signal predicted subsequent left ventricular remodeling at 8 weeks (rpartial = −0.687; p = 0.001). In parallel, brain TSPO signal was elevated at 1 week (1.7 ± 0.2 vs. 1.4 ± 0.2 for sham; p = 0.017), localized to activated microglia. After interval decline at 4 weeks, progressive heart failure precipitated a second wave of neuroinflammation (1.8 ± 0.2; p = 0.005). TSPO was concurrently up-regulated in remote cardiomyocytes at 8 weeks (8.8 ± 1.7, p < 0.001) without inflammatory cell infiltration, suggesting mitochondrial impairment. Angiotensin-converting enzyme inhibitor treatment lowered acute inflammation in the heart (p = 0.003) and brain (p = 0.06) and improved late cardiac function (p = 0.05). Patients also demonstrated elevation of cardiac TSPO signal in the infarct territory, paralleled by neuroinflammation versus controls. The brain is susceptible to acute MI and chronic heart failure. Immune activation may interconnect heart and brain dysfunction, a finding that provides a foundation for strategies to improve heart and brain outcomes. [Display omitted]
ISSN:0735-1097
1558-3597
DOI:10.1016/j.jacc.2017.11.024