Vascular Control of the Secreted Redoxome: An Angiocrine Layer of Communication.

Abstract

Traditionally redox regulation has been interpreted through the lens of intracellular signaling, metabolic adaptation, or oxidative damage. In the vascular system, this view has been particularly influential: endothelial reactive oxygen species, nitric oxide, lipid peroxidation, and antioxidant pathways are commonly discussed as cell-autonomous regulators of vascular tone, permeability, inflammation, angiogenesis, dysfunction or aging. Here, we propose a broader perspective. We argue that the vasculature does not merely experience redox stress; it generates, edits, buffers, packages, and exports redox-active information beyond the traditionally recognized signaling molecules. This exported information-the secreted redoxome-may include oxidatively modified proteins, thiol/disulfide states, extracellular vesicle cargo, and additional circulating redox buffers. We first summarize what is known about vascular oxidative post-translational modifications and circulating redox systems. We then develop the opinion that secreted redox proteins may function as an angiocrine communication layer that instructs tissue homeostasis and disease transition. This view shifts the field from asking how vessels suffer oxidative stress to asking how vessels communicate regulated redox instructions.