Current knowledge on the mechanism of atherosclerosis and pro-atherosclerotic properties of oxysterols

Abstract

Due to the fact that one of the main causes of worldwide deaths are directly related to atherosclerosis, scientists are constantly looking for atherosclerotic factors, in an attempt to reduce prevalence of this disease. The most important known pro-atherosclerotic factors include: elevated levels of LDL, low HDL levels, obesity and overweight, diabetes, family history of coronary heart disease and cigarette smoking. Since finding oxidized forms of cholesterol - oxysterols - in lesion in the arteries, it has also been presumed they possess pro-atherosclerotic properties. The formation of oxysterols in the atherosclerosis lesions, as a result of LDL oxidation due to the inflammatory response of cells to mechanical stress, is confirmed. However, it is still unknown, what exactly oxysterols cause in connection with atherosclerosis, after gaining entry to the human body e.g., with food containing high amounts of cholesterol, after being heated. The in vivo studies should provide data to finally prove or disprove the thesis regarding the pro-atherosclerotic prosperities of oxysterols, yet despite dozens of available in vivo research some studies confirm such properties, other disprove them. In this article we present the current knowledge about the mechanism of formation of atherosclerotic lesions and we summarize available data on in vivo studies, which investigated whether oxysterols have properties to cause the formation and accelerate the progress of the disease. Additionally we will try to discuss why such different results were obtained in all in vivo studies.

Keywords: Atherosclerosis; Cholesterol; Cholesterol oxidation; LDL; Oxysterols.

Fig. 1

Laminar flow disturbances. Once formed, lesion, leads to maintaining flow disturbances and activation of NF-κB in subsequent cells

Fig. 2

Possible transformation of a LDL particle due to a reaction with highly reactive oxygen species

Fig. 3

Main modification of cholesterol due to the oxidation occurring in different sites of the molecule [74, 75]

Fig. 4

Example of non-typical cholesterol modification due to the peroxidation of the side chain, which causes the formation of volatile compounds and a cholesterol derivative, which could possibly undergo another oxidation