Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis: Current Knowledge and Future Perspectives.

Abstract

Atherosclerosis (AS) is characterized by impairment and apoptosis of endothelial cells, continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells, which is documented as the traditional cellular paradigm. However, the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis, transdifferentiation and novel cell death forms such as ferroptosis, pyroptosis, and extracellular trap were reported. Discovery of novel pathological cellular landscapes provides a large number of therapeutic targets. On the other side, the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS burden. Stem cell- or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse effects. Given the complexity of pathological changes of AS, attempts to develop an almighty medicine based on single mechanisms could be theoretically challenging. In this review, the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical translation. The future challenges and improvements were also discussed.