Coronary artery disease (CAD) and its complications are the leading cause of death worldwide. Inflammatory activation and dysfunction of the endothelium are key events in the development and pathophysiology of atherosclerosis and are associated with an elevated risk of cardiovascular events. There is great interest to further understand the pathophysiologic mechanisms underlying endothelial dysfunction and atherosclerosis progression, and to identify novel biomarkers and therapeutic strategies to prevent endothelial dysfunction, atherosclerosis and to reduce the risk of developing CAD and its complications. The use of liquid biopsies and new molecular biology techniques have allowed the identification of a growing list of molecular and cellular markers of endothelial dysfunction, which have provided insight on the molecular basis of atherosclerosis and are potential biomarkers and therapeutic targets for the prevention and or treatment of atherosclerosis and CAD. This review describes recent information on normal vascular endothelium function, as well as traditional and novel potential biomarkers of endothelial dysfunction and inflammation, and pharmacological and non-pharmacological therapeutic strategies aimed to protect the endothelium or reverse endothelial damage, as a preventive treatment for CAD and related complications.

Subclinical coronary atherosclerosis (SCA) is an early stage of coronary artery disease (CAD) that often goes unrecognized until clinical events occur. Identifying circulating molecular biomarkers could improve early diagnosis and risk assessment in asymptomatic individuals. This study employed a two-phase approach to identify plasma extracellular vesicle (EV)-derived microRNAs (miRNAs) associated with SCA. In the discovery phase, plasma samples from male participants were analyzed using Affymetrix GeneChip miRNA 4.0 microarrays. Differentially expressed miRNAs were refined through bioinformatic analysis, cross-species comparison with murine data, and target gene prediction. In the validation phase, six candidate miRNAs were quantified by RT-qPCR in an independent cohort. Six miRNAs were differentially expressed between individuals with SCA and controls. Among these, the combination of miR-146b-5p, miR-4701-3p, and miR-1180-3p demonstrated a high discriminative capacity for SCA (AUC = 0.8281; sensitivity = 93.75%; specificity = 93.75%). Functional enrichment analysis revealed that predicted target genes are involved in key atherosclerosis-related pathways, including inflammation, lipid metabolism, and vascular remodeling. EV-derived miRNAs may serve as non-invasive biomarkers for the early detection of coronary atherosclerosis. These findings provide insight into the molecular processes underlying subclinical vascular disease and support the integration of EV-associated miRNAs into preventive cardiology strategies.