The Role of Immune Cell Types in Ischemic Heart Disease Progression: A Systematic Review

Abstract

Introduction: Globally, Myocardial Ischemia or Ischemic Heart Disease (IHD) inflicts 126 million individuals, totaling an estimated nine million deaths annually. IHD injury and healing are characterized by recruitment of several immune cell types to the cardiac tissue. In addition, atherosclerosis, a common causative factor of IHD, is initiated by mediators of innate and adaptive immunity, thus providing the rationale for studying the role of immune cell types in myocardial ischemia. Clarifying the functions and interactions among these cell types will inform drug targeting studies and ultimately facilitate development of IHD treatment and prevention approaches. Methods: This systematic review highlights and summarizes pertinent studies evidencing the function and interaction of macrophages, monocytes, lymphocytes, platelets, and endothelial cells in IHD pathology. Electronic databases searched consist of Ovid, PubMed, Google Scholar, Web of Science, and ScienceDirect. Keywords include: “immune cells”, “innate immunity”, “inflammation”, “cardiac macrophages”, “adaptive immunity”, “lymphocytes”, “B cells”, “T cells”, “T-regulatory cells”, “myocardial infarction”, “reperfusion”, and additional related keywords. Results: Macrophages, monocytes, lymphocytes, platelets, and endothelial cells interact under innate and adaptive immune responses to initiate and sustain inflammation in cardiac tissue. Sustained inflammation signals for the recruitment of associated molecules to the site of ischemic heart damage which instigate injury and healing processes. Discussion: Building a comprehensive picture of interacting cell types enables the identification of druggable targets and potential treatment and prevention options. Here, we propose several steps of IHD pathology during which further studies with agonist and inhibitor molecules may yield fruitful treatment directions. Lastly, we discuss study limitations and future research avenues. Conclusions: Overall, explicating the immune cell type function and interactions will build a connective understanding of IHD pathology. In turn, elucidating the molecular and cell-specific mechanisms of the inflammatory immune response in cardiomyopathies will aid in the modelling of IHD disease progression as well as facilitate the identification of potential biomarkers and druggable targets to alleviate heart failure disease burden.