Simple SummaryThe role of exosomal non-coding RNA (ncRNA) in regulating macrophage polarization and the role of polarized macrophages as an important source of extracellular vesicles in cardiovascular diseases remains to be elucidated. In this review, we aim to summarize the role and molecular mechanisms of exosomal-ncRNA in regulating macrophage polarization and contributing to cardiovascular diseases. We also discuss the role of polarized macrophages and their derived extracellular vesicles as well as the therapeutic prospects of exosomal ncRNA in the treatment of cardiovascular diseases.AbstractExtracellular vesicles (EVs) or exosomes are nanosized extracellular particles that contain proteins, DNA, non-coding RNA (ncRNA) and other molecules, which are widely present in biofluids throughout the body. As a key mediator of intercellular communication, EVs transfer their cargoes to target cells and activate signaling transduction. Increasing evidence shows that ncRNA is involved in a variety of pathological and physiological processes through various pathways, particularly the inflammatory response. Macrophage, one of the body’s “gatekeepers”, plays a crucial role in inflammatory reactions. Generally, macrophages can be classified as pro-inflammatory type (M1) or anti-inflammatory type (M2) upon their phenotypes, a phenomenon termed macrophage polarization. Increasing evidence indicates that the polarization of macrophages plays important roles in the progression of cardiovascular diseases (CVD). However, the role of exosomal ncRNA in regulating macrophage polarization and the role of polarized macrophages as an important source of EV in CVD remains to be elucidated. In this review, we summarize the role and molecular mechanisms of exosomal-ncRNA in regulating macrophage polarization during CVD development, focusing on their cellular origins, functional cargo, and their detailed effects on macrophage polarization. We also discuss the role of polarized macrophages and their derived EV in CVD as well as the therapeutic prospects of exosomal ncRNA in the treatment of CVD.