Myocardial Inflammation Predicts Remodeling and Neuroinflammation After Myocardial Infarction

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:71

Article

Thackeray, James T.¹  Hupe, Henri C.¹  Wang, Yong²  Bankstahl, Jens P.¹  Berding, Georg¹  Ross, Tobias L.¹  Bauersachs, Johann²  Wollert, Kai C.²  Bengel, Frank M.¹ 

[1] Hannover Med Sch, Dept Nucl Med, Carl Neuberg Str 1, D-30625 Hannover, Germany

[2] Hannover Med Sch, Dept Cardiol & Angiol, Hannover, Germany

关键词: heart failure;    inflammation;    macrophages;    myocardial infarction;    neurodegeneration;    positron emission tomography;   

DOI  :  10.1016/j.jacc.2017.11.024

来源: Elsevier

【 摘 要 】

BACKGROUND The local inflammatory tissue response after acute myocardial infarction (MI) determines subsequent healing. Systemic interaction may induce neuroinflammation as a precursor to neurodegeneration. OBJECTIVES 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. METHODS 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). RESULTS 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 (r(partial) = -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. CONCLUSIONS 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. (c) 2018 by the American College of Cardiology Foundation.

【 授权许可】

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