Novel insight on the role of Macrophages in atherosclerosis: Focus on polarization, apoptosis and efferocytosis

Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases, which is mainly characterized by lipid deposition and inflammatory response. Macrophages (MΦ), as the key mediators of the inflammatory response, run through all stages of the occurrence and development of AS, from plaque initiation to the transition to vulnerable plaques, and are regarded as important therapeutic targets. It was previously thought that the atherogenic mechanism of MΦ was mainly due to their phagocytosis of lipids, resulting in excessive foam cells aggregated on the arterial wall. However, increasing evidence has revealed the diversity of AS mechanisms caused by MΦ. For example, MΦ present a continuum phenotypic spectrum, and their polarization has been demonstrated to play a vital role in the regulation of AS-related inflammatory response. MΦ apoptosis and the ability of MΦ to clean up apoptotic cells (also known as efferocytosis) are crucial determinants of AS lesion progression and plaque stability. Hence, this review probes into the contradictory regulation of MΦ on AS based on polarization, apoptosis, and efferocytosis, designed to highlight the complex and interrelated regulated network of MΦ promoting AS.