BACKGROUND:  Atherosclerosis is the development of lesions in blood vessel walls, which can progress to cardiovascular disease. Macrophage Colony Stimulating Factor (M-CSF) is a growth factor that plays a role in the progression of these atherosclerotic lesions by activating immune cells called monocytes. Monocytes enter artery walls and begin thickening and remodeling the walls, which therefore leads to atherosclerosis. Research on M-CSF has been unable to identify the mechanisms of how M-CSF contributes to lesion development. Not only is there a need to determine the ways M-CSF contributes to lesion development, there is also a need for therapeutics that can specifically target the inflammation and lesion development that occurs at the beginning stages of atherosclerosis.

INNOVATION:  UCLA researchers have identified that a selective kinase inhibitor is able to suppress the development of atherosclerosis. As well, investigators are able to determine that vascular cell-derived M-CSF, rather than macrophage-derived M-CSF is primarily involved in atherosclerotic lesion formation. Selective kinase inhibitor experiments with mice have shown that inhibition of M-CSF signaling within artery walls decreases inflammation and lesion formation. These experiments also suggest that the mechanisms for M-CSF's effect on atherosclerosis involve monocyte recruitment and macrophage survival. The selective kinase inhibitor acts to decrease monocyte migration into artery walls and decrease macrophage survival within artery walls.

POTENTIAL APPLICATIONS 

• A selective kinase inhibitor may be used as a therapeutic to treat atherosclerosis by decreasing lesions within artery walls
• M-CSF+/- LDLR-/- mice can be used for further experiments relating to atherosclerosis

ADVANTAGES

• Selective kinase inhibitor may suppress atherosclerotic lesion formations without altering lipid levels, body composition, or bone density
• Selective kinase inhibitor may work in conjunction with anti-platelet agents, heparin or other anti-thrombosis, anti-coagulation therapies
• Selective kinase inhibition does not trigger harmful physiological problems associated with the complete inhibition of M-CSF signaling

DEVELOPMENT-TO-DATE:  M-CSF+/- LDLR-/- mouse models have been used to test a selective kinase inhibitor to treat atherosclerosis. Researchers have validated that the selective kinase inhibitor suppresses inflammation and lesion formation while not triggering deleterious physiological problems observed with complete inhibition of M-CSF signaling.

Reference: UCLA Case No. 2008-490