Cellular and Molecular Mechanisms of Vascular Endothelial Injury Induced by Cigarette Smoke and Cigarette Smoke Extract in Atherosclerosis.

Although smoking is a well-recognized independent risk factor for atherosclerosis (AS), its core pathogenic mechanism lies in the induction of vascular endothelial cell (VEC) dysfunction, which represents the initial step of AS development. However, the mechanisms by which cigarette smoke (CS) and cigarette smoke extract (CSE) trigger and promote atherosclerotic progression via VECs remain incompletely understood. CS and CSE damage the vascular endothelial barrier through three key mechanisms: oxidative stress induction, inflammatory response activation, and endothelial cell apoptosis. This narrative review summarizes the cellular and molecular mechanisms by which CS and CSE disrupt vascular endothelial cell function through activation of the nuclear factor kappa B (NF-κB) signaling pathway, the nitric oxide (NO) synthesis pathway, and the mitogen-activated protein kinase (MAPK) signaling pathway, based on experimental studies at the cellular and organ levels. This review aims to provide a novel perspective for clarifying the pathological basis of smoking-induced atherosclerosis and lay a foundation for the development of intervention strategies targeting endothelial protection.