Identify the initial signal cascades that trigger macrophage recruitment in early atherosclerosis

Determine the specific molecular signal cascade(s) that initially stimulate monocyte-derived macrophage recruitment to the intima in early human atherosclerotic lesions in response to retained low-density lipoprotein (LDL), including the identities, sources, and spatiotemporal dynamics of the inflammatory mediators produced by resident cells that drive the recruitment process.

Background

In the model, the authors introduce an equation for inflammatory mediators S and assume S is produced by resident cells proportionally to retained LDL (rLDL), consistent with the response-to-retention hypothesis. However, they acknowledge that the precise initiating signaling events are unknown and thus model the mediator production phenomenologically.

Clarifying these early signaling cascades would improve mechanistic understanding and allow more accurate model specification of mediator sources, production kinetics, and coupling to monocyte-derived macrophage recruitment.