Abstract and Introduction
Abstract
Graphical Abstract
To better treat the residual risk conferred by inflammation in atherosclerosis, a triad of three novel strategies can be envisioned. Immune cell recruitment can be targeted by specific interference with the CXC chemokine receptor (CXCR4) axis and its ligands CXCL12 or MIF. Immune cell function can be modulated by selective targeting the interaction between the co-stimulatory molecule CD40 and the TNF-receptor associated factor TRAF6. Recently identified neuroimmune cardiovascular interfaces regulating atherosclerosis and their connectivity in neuronal circuits could be specifically targeted by surgical, pharmaceutical, or bioelectronics methods.
This review based on the ESC William Harvey Lecture in Basic Science 2022 highlights recent experimental and translational progress on the therapeutic targeting of the inflammatory components in atherosclerosis, introducing novel strategies to limit side effects and to increase efficacy. Since the validation of the inflammatory paradigm in CANTOS and COLCOT, efforts to control the residual risk conferred by inflammation have centred on the NLRP3 inflammasome-driven IL-1β-IL6 axis. Interference with the co-stimulatory dyad CD40L–CD40 and selective targeting of tumour necrosis factor-receptor associated factors (TRAFs), namely the TRAF6–CD40 interaction in macrophages by small molecule inhibitors, harbour intriguing options to reduce established atherosclerosis and plaque instability without immune side effects.
