Free cholesterol in atherosclerotic plaques: where does it come from?

Free cholesterol in plaques is an emerging contributing factor to lesion instability and, until recently, apoptosis of lipid-laden macrophages was considered the major source of free cholesterol. The validity of this concept is beginning to be challenged since there is recent evidence of erythrocyte membrane-derived cholesterol in plaques. Therefore, intraplaque hemorrhage may not be a passive event, as once considered as studies continue to support the relationship of intraplaque hemorrhage and necrotic core expansion.

The association of intraplaque hemorrhage, accumulated free cholesterol, and necrotic core expansion is beginning to unfold and recent MRI studies suggest the value of intraplaque hemorrhage as a predictor of recurrent cerebrovascular events. The amount of erythrocyte membrane-derived cholesterol is also suggested to be a measure of lesion vulnerability in acute coronary syndromes. Recent inhibitors studies of vascular permeability factors further emphasize the importance of intraplaque hemorrhage in plaque progression. Finally, DNA microarray analysis is starting to reveal key molecules involved in the accumulation of free cholesterol that are selectively induced in high-risk plaques.

These recent findings emphasize the importance of intraplaque hemorrhage as a contributor of free cholesterol in plaques and point to its provocative role in lesion destabilization.