Aernoud Fiolet

66 Chapter 2 CONCLUSIONS AND FUTURE DIRECTIONS Viewing atherosclerosis“througha crystal lens”presents aparadigm,whichexplains how the evolving nature of cholesterol in atherosclerotic plaque affects the risk of vascular injury. Specifically, how the continuous spontaneous assembly of excess free cholesterol in the intracellular and extracellular space within atherosclerotic plaque leads to the formation of metastable tubular crystalline structures that can transition into flat plate CCs, which persist and expose atherosclerotic plaque to the constant threat of inflammatory and traumatic injury. Development of therapies that further limit the deposition of free cholesterol in the vascular bed, slow the formation of metastable CCs and their transformation into flat plate structures and inhibit crystal-induced inflammation, will likely further reduce residual CV risk in patients with established CV disease. Table 1. Potential ways to reduce the impact of cholesterol crystals in atherosclerosis Prevent formation of metastable structures Dissolve metastable structures Alter the morphology of flat plate CCs