Succinate: A Novel Mediator to Promote Atherosclerotic Lesion Progression.

Succinate is an important intermediate product of mitochondrial energy metabolism. Recent studies revealed that beyond its known traditional metabolic functions, succinate plays important roles in signal transduction, immunity, inflammation, and posttranslational modification. Recent studies showed that patients and mouse models with cardiovascular disease have high levels of serum succinate and succinate accumulation. Atherosclerosis (As) is the pathological basis of cardiovascular and peripheral vascular diseases, such as coronary heart disease, cerebral infarction, and peripheral vascular disease, and is a major factor affecting human health. This article reviews the progression of succinate in As diseases and its underlying mechanisms.

Krebs Cycle Rewired: Driver of Atherosclerosis Progression?

The tricarboxylic acid (TCA) cycle is the center of energy metabolism in eukaryotic cells and is dynamically adjusted according to the energy needs of cells. Macrophages are activated by inflammatory stimuli, and then two breakpoints in TCA cycle lead to the accumulation of intermediates. Atherosclerosis is a chronic inflammatory process. Here, the "non-metabolic" signaling functions of TCA cycle intermediates in the macrophage under inflammatory stimulation and the role of intermediates in the progression of atherosclerosis are discussed.

PD-1/PD-L1 immune checkpoints: Tumor vs atherosclerotic progression.

Immunotherapy has become one of the most attraction cancer therapy strategies. The PD-1/PD-L1 pathway plays key roles in immune responses and autoimmunity by regulating T cell activity. Overactivation of this pathway dampens T cell and immune function, which allows tumor cells immune escape. Antibody or inhibitors of PD-1/PD-L1 immune targets have been implicated in clinic anti-cancer therapy and gain great clinic outcoming for their high efficiency. However, recent studies showed that the PD-1/PD-L1 immunotherapy in some tumor patients was found to accelerate T cell-driven inflammatory and the progression of atherosclerotic lesions. This article reviews the research progression of PD-1/PD-L1 in tumors and atherosclerosis, and the possible mechanisms of anti-PD-1/PD-L1 immunotherapy increasing the risk of atherosclerotic lesions.

Low shear stress induced vascular endothelial cell pyroptosis by TET2/SDHB/ROS pathway.

Vascular endothelial cell (VEC) inflammation induced by low shear stress plays key roles in the initiation and progression of atherosclerosis (As). Pyroptosis is a form of inflammatory programmed cell death that is critical for As. However, the effect of low shear stress on VEC pyroptosis and the underlying mechanisms were not clear. Here we show that low shear stress promoted VEC pyroptosis and reduced the expression of Ten-Eleven Translocation 2 (TET2) methylcytosine dioxygenase. Loss of TET2 resulted in the upregulation of the expression and activity of mitochondrial respiratory complex II subunit succinate dehydrogenase B (SDHB) by decreasing the recruitment of histone deacetylase 2, independent of DNA demethylation modification. The overexpression of SDHB mediated mitochondrial injury and increased the production of reactive oxygen species (ROS). The administration of ROS scavenger NAC alleviated VEC pyroptosis induced by SDHB overexpression and TET2 shRNA. These findings show that low shear stress induced endothelial cell pyroptosis through the TET2/SDHB/ROS pathway and offer new insights into As.