"How to Release or Not Release, That Is the Question." A Review of Interleukin-1 Cellular Release Mechanisms in Vascular Inflammation

Cardiovascular disease remains the leading cause of death worldwide, characterized by atherosclerotic activity within large and medium-sized arteries. Inflammation has been shown to be a primary driver of atherosclerotic plaque formation, with interleukin-1 (IL-1) having a principal role. This review focuses on the current state of knowledge of molecular mechanisms of IL-1 release from cells in atherosclerotic plaques. A more in-depth understanding of the process of IL-1's release into the vascular environment is necessary for the treatment of inflammatory disease processes, as the current selection of medicines being used primarily target IL-1 after it has been released. IL-1 is secreted by several heterogenous mechanisms, some of which are cell type-specific and could provide further specialized targets for therapeutic intervention. A major unmet challenge is to understand the mechanism before and leading to IL-1 release, especially by cells in atherosclerotic plaques, including endothelial cells, vascular smooth muscle cells, and macrophages. Data so far indicate a heterogeneity of IL-1 release mechanisms that vary according to cell type and are stimulus-dependent. Unraveling this complexity may reveal new targets to block excess vascular inflammation.