Iranshahy M, Banach M, Hasanpour M, Lavie CJ, Sahebkar A
Cholesterol crystals (CCs) play a key role in the pathophysiology of cardiovascular diseases (CVD) via triggering inflammation, plaque formation and subsequently plaque rupture. Although statins can stabilize plaques via calcification and alteration of the lipid composition within plaques, there is still a high residual risk of CVD events among statins users. Several studies have tried to blunt the detrimental effects of cholesterol crystals by pharmacological interventions. Cyclodexterins (CDs) and other nanoformulations, including polymers of CDs and liposomes, have the ability to dissolve CCs in vitro and in vivo. CDs were the first in their class that entered clinical trials and showed promising results, though their ototoxicity outweighed their benefits. Moreover, small molecules with structural similarity to cholesterol may also perturb cholesterol-cholesterol interactions and prevent from expansion of 2D crystalline domains to large 3D CCs. The results from ethyl eicosapentaenoic acid and ursodeoxycholic acid were encouraging and worth further consideration. In this review, the significance of CCs in pathogenesis of CVD is discussed and pharmacological agents with the ability to dissolve CCs or prevent from CCs formation are introduced.