Mechanisms of pericardial adipose tissue activation after myocardial infarction

点击翻译按钮获取中文摘要

Acute myocardial infarction (MI) is the leading cause of mortality and morbidity in Europe. The lack of oxygen and nutrient supply leads to necrosis of a large number of cardiomyocytes, which induces an inflammatory response. This is followed by the formation of a fibrous scar and remodeling processes that may progressively lead to impaired cardiac function and heart failure. Past research investigating the underlying inflammatory mechanisms and cellular key players of cardiac repair mainly focused on cells within the heart. However, the relevance of the perivascular adipose tissue, in particular the adipose tissue surrounding coronary arteries and myocardium in MI healing and clinical outcome has been largely neglected so far.Based on our previous discovery that pericardial adipose tissue (PAT) contains clusters of immune cells that are activated after MI, the overarching aim of this project is to clarify how the PAT senses cardiac injury, and what are the factors leading to immune cell activation within pericardial lymphoid clusters. To address this question, we will focus on 3 specific aims: (1) We hypothesize that adrenergic nerves control pericardial FALC immune cell activation. (2) We want to clarify whether MI promotes lymphangiogenesis within PAT. What are the characteristics of pericardial microvessels, which are in contact with pericardial FALCs? (3) We further hypothesize that non-classical monocytes serve as antigen presenting cells by displaying cardiac antigens on their surface, thereby contributing to pericardial lymphocyte activation. Moreover, we will investigate whether our recently identified specific marker for non-classical monocytes (CD274/PD-L1) can be therapeutically blocked to improve cardiac outcome after MI. This will be complemented by studying the impact of genetic non-classical monocyte deficiency on MI outcome.Our approach focusing on the myocardium-adipose crosstalk that orchestrates cardiac injury, repair and remodeling processes opens a completely novel concept. A better understanding of the mechanisms involved in pericardial immune cell activation may help developing new therapeutic strategies to improve the clinical outcome for MI patients.