Myocardial Inflammation Predicts Remodeling and Neuroinflammation After Myocardial Infarction. 2018

James T Thackeray, and Henri C Hupe, and Yong Wang, and Jens P Bankstahl, and Georg Berding, and Tobias L Ross, and Johann Bauersachs, and Kai C Wollert, and Frank M Bengel
Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.

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.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009203 Myocardial Infarction NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION). Cardiovascular Stroke,Heart Attack,Myocardial Infarct,Cardiovascular Strokes,Heart Attacks,Infarct, Myocardial,Infarction, Myocardial,Infarctions, Myocardial,Infarcts, Myocardial,Myocardial Infarctions,Myocardial Infarcts,Stroke, Cardiovascular,Strokes, Cardiovascular
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D005544 Forecasting The prediction or projection of the nature of future problems or existing conditions based upon the extrapolation or interpretation of existing scientific data or by the application of scientific methodology. Futurology,Projections and Predictions,Future,Predictions and Projections
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D057054 Molecular Imaging The use of molecularly targeted imaging probes to localize and/or monitor biochemical and cellular processes via various imaging modalities that include RADIONUCLIDE IMAGING; ULTRASONOGRAPHY; MAGNETIC RESONANCE IMAGING; FLUORESCENCE IMAGING; and MICROSCOPY. Imaging, Molecular
D020257 Ventricular Remodeling The geometric and structural changes that the HEART VENTRICLES undergo, usually following MYOCARDIAL INFARCTION. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle. Cardiac Remodeling, Ventricular,Left Ventricular Remodeling,Myocardial Remodeling, Ventricular,Left Ventricle Remodeling,Ventricle Remodeling,Cardiac Remodelings, Ventricular,Left Ventricle Remodelings,Left Ventricular Remodelings,Myocardial Remodelings, Ventricular,Remodeling, Left Ventricle,Remodeling, Left Ventricular,Remodeling, Ventricle,Remodeling, Ventricular,Remodeling, Ventricular Cardiac,Remodeling, Ventricular Myocardial,Remodelings, Left Ventricle,Remodelings, Left Ventricular,Remodelings, Ventricle,Remodelings, Ventricular,Remodelings, Ventricular Cardiac,Remodelings, Ventricular Myocardial,Ventricle Remodeling, Left,Ventricle Remodelings,Ventricle Remodelings, Left,Ventricular Cardiac Remodeling,Ventricular Cardiac Remodelings,Ventricular Myocardial Remodeling,Ventricular Myocardial Remodelings,Ventricular Remodeling, Left,Ventricular Remodelings,Ventricular Remodelings, Left

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