Liang Hong

Atherosclerosis is a chronic inflammatory disease characterized by progressive vascular dysfunction and remains a leading cause of cardiovascular morbidity and mortality worldwide. Endothelial dysfunction is an early and critical event in atherogenesis, contributing to inflammation, leukocyte recruitment, plaque progression, and thrombotic complications. Increasing evidence indicates that vascular endothelial cells use bioelectrical signaling mechanisms to integrate mechanical, metabolic, and inflammatory cues and maintain vascular homeostasis. At the core of these regulatory networks are ion channels and transporters, which coordinate membrane potential, ionic fluxes, calcium homeostasis, redox balance, and downstream biochemical signaling to regulate endothelial function in vascular health and disease. Dysregulation of these pathways may promote oxidative stress, inflammation, endothelial senescence, apoptosis, endothelial-to-mesenchymal transition, and impaired vasodilatory function, thereby contributing to atherosclerotic progression. Understanding how ion channels regulate endothelial function may provide important insights into atherosclerosis and facilitate the development of novel therapeutic strategies aimed at restoring endothelial homeostasis and reducing cardiovascular risk.

Atherosclerosis (AS) is a severe vascular disease that results in millions of cases of mortality each year. The development of atherosclerosis is associated with vascular structural lesions, characterized by the accumulation of immune cells, mesenchymal cells, lipids, and an extracellular matrix at the intimal resulting in the formation of an atheromatous plaque. AS involves complex interactions among various cell types, including macrophages, endothelial cells (ECs), and smooth muscle cells (SMCs). Endothelial dysfunction plays an essential role in the initiation and progression of AS. Endothelial dysfunction can encompass a constellation of various non-adaptive dynamic alterations of biology and function, termed “endothelial reprogramming”. This phenomenon involves transitioning from a quiescent, anti-inflammatory state to a pro-inflammatory and proatherogenic state and alterations in endothelial cell identity, such as endothelial to mesenchymal transition (EndMT) and endothelial-to-immune cell-like transition (EndIT). Targeting these processes to restore endothelial balance and prevent cell identity shifts, alongside modulating epigenetic factors, can attenuate atherosclerosis progression. In the present review, we discuss the role of endothelial cells in AS and summarize studies in endothelial reprogramming associated with the pathogenesis of AS.

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Atherosclerosis is a complex inflammatory disease that affects the arteries and can lead to severe complications such as heart attack and stroke. Macrophages, a type of immune cell, play a crucial role in atherosclerosis initiation and progression. Emerging studies revealed that ion channels regulate macrophage activation, polarization, phagocytosis, and cytokine secretion. Moreover, macrophage ion channel dysfunction is implicated in macrophage-derived foam cell formation and atherogenesis. In this context, exploring the regulatory role of ion channels in macrophage function and their impacts on the progression of atherosclerosis emerges as a promising avenue for research. Studies in the field will provide insights into novel therapeutic targets for the treatment of atherosclerosis.