The Behaviour of Cardiac Macrophages in the Steady State, Injured, and Ageing Heart: A Systematic Review

Abstract

Introduction: Research conducted over the past decade has revealed that the heart is home to both recruited and tissue-resident macrophages, both of which play a vital role in cardiac development, composition, and function. Moreover, clinical studies have demonstrated that tissue-resident macrophages contribute considerably to a variety of regulatory and housekeeping tasks in the homeostatic heart. It has been long established that following cardiac injury, macrophages work to clear the heart of debris, stimulate the regeneration of damaged tissue and stabilize the cardiac wall. However, much remains elusive about the exact nature of cardiac macrophages. Hence, this review will analyze and summarize the current literature documenting the critical roles, origins, phenotypes and biomechanisms of macrophages in cardiac homeostasis and cardiac disease. Methods: An overarching map depicting the relationship between cardiac macrophages and the cardiac environment was assembled via a systematic review of the extant literature on the origins, phenotypes, biochemical profiles and biomechanisms of cardiac macrophages. In total, 28 works were analyzed to determine the importance of macrophages in the homeostatic, injured, and ageing heart. Results: Research conducted over the past decade shows that the heart is home to a heterogeneous population of cardiac macrophages. Contrary to the historic perspective that all cardiac macrophages are derived from circulating blood monocytes, evidence has demonstrated that most of these macrophages are of embryonic origin. Extant literature has identified various subsets, each of which appears to be responsible for either reparative or inflammatory tasks. Discussion: It is foreseen that developing a more comprehensive understanding of cardiac macrophages may open new doors to novel therapeutic methods for cardiac diseases and disorders. The advancement of treatment procedures post heart failure may be a vital step in lowering the frequency of periodic episodes amongst patients with chronic heart dysfunctions. Conclusion: The observed behaviour of murine and human cardiac macrophages in various cardiac conditions has led to the development of three main perspectives: one, a macrophage’s ontogeny dictates its function; two, the local cardiac tissue dictate macrophage function; and three, the nature versus nurture argument is a false dichotomy.