Oxysterols progression

Cholesterol is absorbed by intestinal epithelial cells via a Niemann-Pick Cl-Like 1 (NPCILI) protein. This is the target of a number of anti-hyperhpidaemic drugs used to lower cholesterol levels. Examples include miglustafi aUopregnanolone, oxysterols and cyclodextrins all are able to slow the progress of the disease, but none as yet provides an... 

In summary, oxysterols are known to exist in atherosclerotic lesions and have been demonstrated in cell-culture experiments to have profound cellular effects that could influence the development, progression, and reversal of atherosclerosis. The key question in this field of research, however, is whether the concentrations of oxysterols in vivo are high enough to influence atherogenesis. Thus far, only the oxysterol-activated nuclear transcription pathway has been directly supported by in vivo data, and even in this case the precise roles and identification of the activating oxysterols in vivo have not yet been elucidated. Moreover, to the extent that oxysterols are generated in vivo and not just obtained from the diet, their role in human atherosclerosis has been questioned by clinical trials showing little or no protective effect of antioxidants on atherosclerotic coronary artery disease (K.J. Williams and E.A. Fisher, 2005). 

Is There a Dual Effect of Oxysterols on Atherosclerotic Plaque Progression .313... 

Another important finding is that mmLDL contains mainly phospholipid oxidation products, while the oxysterol content increases proportionally with the oxidation rate (Shentu et al. 2012). Taken together, these very recent experimental reports and reviews suggest a primary role for oxysterols in the progression of atherosclerosis, rather than in its initiation. However, the marked biochemical changes that oxysterols have been found to bring about in endothelial cells (ECs) suggest that the possibility that cholesterol oxides make some contribution to endothelial dysfunction in atherosclerosis should not be discarded a priori. 

IS THERE A DUAL EFFECT OF OXYSTEROLS ON ATHEROSCLEROTIC PLAQUE PROGRESSION ... 

On this basis, a versatile even if contradictory role of oxysterols may emerge, which poses the question of how they actually affect the atherosclerotic lesion development and which factors might modulate their behavior. In this connection, how much does it depend on the nature of oxysterols thanselves (e.g., chemical structure, enzymatic or nonenzymatic origin) and how much on extrinsic factors (e.g., stage of disease progression, cell phenotype, presence of other bioactive compounds) ... 

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