Quest for new biomarkers in atherosclerosis

Abstract

The Cho and Baldan labs focus their efforts on novel pathways that control atherogenesis. MIF (Macrophage migration inhibitory factor) recruits macrophages to atherosclerotic lesions and activates the production of matrix proteinases, which in turn destabilize atherosclerotic plaques. On the other hand, miR-33 coordinates the expression of several sterol transporters essential for high-density lipoprotein metabolism and bile secretion. Thus, both MIF and miR-33 are promising therapeutic targets to manage patients at risk of developing atherosclerosis.

Figure 1

MIF signaling. Crystal structure of a trimeric MIF is shown in cartoon representation. Surface of each monomer is colored differently. Up and down arrows indicate the increase and decrease of disease severity and immunity, respectively, proportional to the physiological concentrations of MIF. Blue bi-directional arrows between the receptors indicate the interaction between the MIF receptors. The large downward arrowhead indicates cellular outcomes of the receptor signals activated by MIF.

Figure 2

Label-free technology for monitoring cellular events. (A) MIF (red) binds to receptors on the cell surface and activates the intracellular signaling events represented as dynamic mass redistribution (DMR, black indicates movement of signaling molecules). Cells are plated on a fibronectin-coated biosensor. (B) DMR is represented as the peak wavelength value difference (delta PWV) before and after the addition of MIF. (C) One of the HTS MIF inhibitors alters the MIF-mediated DMR responses compared to those of MIF alone in panel B.