Platelets could be key regulators of epithelial/endothelial-to- mesenchymal transition in atherosclerosis and wound healing

•Platelets may be regulators of epithelial/endothelial-to-mesenchymal transition.•Platelets may play a key role in atherosclerosis and wound healing.•The modulation of cellular transitions by platelets may be a double-edged sword. Atherosclerosis and wound healing are complex pathophysiological processes involving multiple cell types, including endothelial cells and platelets. Endothelial-to-mesenchymal transition (EndMT) involves the transformation of endothelial cells into mesenchymal cells. This transition serves as a critical mechanism in vascular remodeling, essential for both atherosclerosis pathogenesis and wound healing. On the other hand, epithelial-to-mesenchymal transition (EMT), which involves the transformation of epithelial cells into mesenchymal cells, is crucial for wound healing. Platelets are known to release various growth factors and cytokines which are integral to wound healing and tissue repair, although their direct role in the modulation of EndMT and EMT remains unclear. However, a few studies have shown a potential mechanistic link between platelet activity and these cellular transitions. Since EndMT and EMT play a critical role in vascular remodeling and tissue repair, respectively, it is plausible that these processes are modulated by platelets, which are known for their dynamic and context-dependent release of growth factors and cytokines.Therefore, we postulate that platelets significantly impact the progression of atherosclerosis through the modulation of EndMT, and that of wound healing through the regulation of both EndMT and EMT. The influence of platelets on these processes can have both beneficial and detrimental effects. This hypothesis represents a significant advance in our understanding of the complex interplay between platelets, cellular phenotype, and disease pathophysiology. Elucidating the specific mechanisms by which platelets modulate EMT and EndMT could pave the way for innovative therapeutic strategies that harness the body’s innate capacity for repair and regeneration, thereby enhancing clinical outcomes for these conditions.