Connexome-associated pathways in atherosclerosis and potential regulatory nanomedicine-based strategies

Atherosclerosis remains the primary cause of cardiovascular morbidity and mortality, with intercellular communication critically influencing vascular homeostasis and disease progression. The connexome comprises connexins, pannexins, and associated proteins, and coordinates endothelial, smooth muscle, and immune cell interactions. Krüppel-like factors (KLFs) are key transcriptional regulators that modulate endothelial phenotype, inflammation, and oxidative stress. Advances in nanomedicine provide targeted platforms for modulating these molecular networks, offering novel diagnostic and therapeutic possibilities. This review is integrated by a comprehensive literature review conducted across Pubmed, Scopus, and Web of Science focusing on connexome regulation in vascular biology, and transcriptional control in the context of atherosclerosis. The discussion draws on recent experimental and translational studies linking connexin biology, KLF signaling, and nanomedicine in vascular health and disease. Emphasis is placed on translational evidence for nanoparticle-based delivery systems, including small molecules, nucleic acids, and imaging agents designed to target vascular lesions, with attention to strategies that improve specificity and bioavailability. The convergence of nanomedicine with connexome and KLF-targeted interventions could redefine atherosclerosis management by enabling precision drug delivery and real-time monitoring. Achieving clinical translation will require overcoming challenges related to nanoparticle biocompatibility, targeted biodistribution, immune compatibility, and long-term safety to fully realize their therapeutic potential.