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.

Neutrophil Extracellular Traps (NETs) and Atherosclerosis: Does Hypolipidemic Treatment Have an Effect?

“…The recent advancements in understanding molecular and cellular mechanisms in atherosclerosis, as well as future perspectives, have been described [ 2 ]. Accumulating evidence suggests that inflammation is the key component linking risk factors with atherosclerosis [ 18 ].…”

“…Extracellular traps (ETs) are large, web-like structures composed of decondensed DNA, and the process of ET formation is known as ETosis [ 1 ]. While neutrophil ETtosis (NETosis) was initially used to describe a new form of neutrophil death, different from apoptosis, necrosis, and necroptosis [ 1 ], evidence of ETs has also been reported for macrophages, eosinophils, basophils, mast cells, and dendritic cells [ 2 ]. Although neutrophil extracellular traps (NETs) are thought to be an evolutionary, conserved defensive element due to their protective abilities like trapping, killing, and restraining microorganisms, it is their vast pathogenic potential that has recently emerged as a research topic of great interest [ 3 , 4 ].…”