Immunity strikes: heart failure as a systemic disease (original) (raw)
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Monocyte recruitment and fate specification after myocardial infarction
American Journal of Physiology-Cell Physiology
Monocytes are critical mediators of the inflammatory response following myocardial infarction (MI) and ischemia-reperfusion injury. They are involved in both initiation and resolution of inflammation and play an integral role in cardiac repair. The antagonistic nature of their function is dependent on their subset heterogeneity and biphasic response following injury. New advancements in single-cell transcriptomics and mass cytometry have allowed us to identify smaller, transcriptionally distinct clusters that may have functional relevance in disease and homeostasis. Additionally, recent insights into the spatiotemporal dynamics of monocytes following ischemic injury and their subsequent interactions with the endothelium and other immune cells reveal a complex interplay between monocytes and the cardiac milieu. In this review, we highlight recent findings on monocyte functional heterogeneity, present new mechanistic insight into monocyte recruitment and fate specification following M...
Clinical & Experimental Immunology
Activation of the innate immune response following myocardial infarction (MI) is essential for infarct repair. Preclinical models of MI commonly use C57BL/6 mice, which have a type 1-dominant immune response, whereas other mouse strains such as BALB/c mice have a type 2-dominant immune response. We compared C57BL/6 and BALB/c mice to investigate whether predisposition towards a proinflammatory phenotype influences the dynamics of the innate immune response to MI and associated infarct healing and the risk of cardiac rupture. MI was induced by permanent coronary artery ligation in 12-15-week-old male wild-type BALB/c and C57BL/6 mice. Prior to MI, C57BL/6 mice had a lower proportion of CD206 + anti-inflammatory macrophages in the heart and an expanded blood pool of proinflammatory Ly6C high monocytes in comparison to BALB/c mice. The systemic inflammatory response in C57BL/6 mice following MI was more pronounced, with greater peripheral blood Ly6C high monocytosis, splenic Ly6C high monocyte mobilization and myeloid cell infiltration of pericardial adipose tissue. This led to an increased and prolonged macrophage accumulation, as well as delayed transition towards anti-inflammatory macrophage polarization in the infarct zone and surrounding tissues of C57BL/6 mice. These findings accompanied a higher rate of mortality due to cardiac rupture in C57BL/6 mice compared with BALB/c mice. We conclude that lower post-MI survival of C57BL/6 mice over BALB/c mice is mediated in part by a more pronounced and prolonged inflammatory response. Outcomes in BALB/c mice highlight the therapeutic potential of modulating resolution of the innate immune response following MI for the benefit of successful infarct healing.
Circulation Journal, 2010
Background: The presence of microvascular obstruction (MVO) after primary ST-segment elevation acute myocardial infarction (STEMI) is associated with a poor outcome. The aim of the paper was to examine the relationship between distinct monocyte subsets and gadolinium-enhanced cardiovascular magnetic resonance (CMR) characteristics of MVO after STEMI. Methods and Results: Seventy-one patients with primary STEMI successfully treated with stenting were enrolled in the study. Two monocyte subsets (CD14 + CD16and CD14 + CD16 +) were measured on flow cytometry on admission and 2, 3, 4, 5, 8 days after the onset of STEMI. CMR was performed 7 days after revascularization to determine MVO on late gadolinium-enhanced imaging. The peak levels of CD14 + CD16monocytes, but not those of CD14 + CD16 + monocytes, were significantly higher in patients with MVO than in those without MVO. A multivariate logistic regression model showed that the post-perfusion peak levels of CD14 + CD16monocytes remained an independent factor for the presence of MVO (odds ratio=1.53; 95% confidence interval: 1.01-2.32; P=0.04). The absence of MVO was significantly associated with improvement in left ventricular ejection fraction. Conclusions: Post-reperfusion enhancement of CD14 + CD16monocytes was associated with MVO in patients with STEMI. The pathophysiologic and therapeutic implications of this association require further study.