Macrophage-endothelial cell crosstalk drives atherosclerotic plaque formation and progression

Atherosclerosis (AS) is a chronic disease driven by maladaptive processes and unresolved inflammatory responses, characterized by endothelial dysfunction and subsequent macrophage activation. During the early stages of atherosclerotic pathogenesis, circulating monocytes are recruited by the damaged endothelial cell (EC) layer, subsequently adhering to and migrating into the subendothelial space. There, in response to local cytokines and low-density lipoprotein (LDL), the infiltrated monocytes differentiate into macrophages, which constitute the major immune cells accumulating in atherosclerotic plaques. Intercellular communication facilitates the functional coordination between different cell types within tissues, which is a hallmark of multicellular organisms and a crucial process in both physiological and pathological responses. In the pathogenesis of vascular diseases, the dynamics of multicellular responses play a critical role in the progression and regression of lesions. The interaction between immune cells and dysfunctional endothelial cells is considered an early event in the initiation of the inflammatory cascade and is also recognized as a significant contributing factor in the pathological progression of atherosclerotic vascular diseases. Therefore, elucidating the interactions between various cell types during the progression of atherosclerotic lesions is of significant importance for understanding atherosclerosis. Additionally, this understanding will aid in developing targeted therapies in the future. In this review, we explore how macrophage-endothelial cell crosstalk contributes to the disease from multiple aspects of atherosclerotic pathogenesis, focusing on three critical pathological processes: inflammation, lipid metabolism alterations, and endothelial injury. Furthermore, we summarize the non-coding RNAs involved in this process, aiming to provide valuable new targets for the treatment of atherosclerosis.