The atheroprotective effect of HDL is well-established, the implication being that the higher the plasma levels of HDL,the bigger the benefit to all individuals.Such a supposition has led to the development of "H...The atheroprotective effect of HDL is well-established, the implication being that the higher the plasma levels of HDL,the bigger the benefit to all individuals.Such a supposition has led to the development of "HDL therapy".It has fast become apparent however that assuming therapeutic benefits by merely raising HDL levels is highly simplistic.The most established atheroprotective function of HDL is its role in reverse cholesterol transport(RCT). However other functions of HDL not directly related to RCT may also contribute significantly to its atheioprotective properties.As well,there are many examples where the functionality of HDL changes discordantly to its concentration such that high levels of HDL can be pro-rather than antiatherogenic under certain metabolic conditions.In humans,the ability of HDL to support cholesterol efflux and maintain endothelial function,or antioxidant function can be diminished despite higher HDL levels.Conversely, apoA-IMilano mutation leads to lower HDL levels,but enhances HDL functionality.We and others have recently shown that HDL also has potent anti-inflammatory actions and can also influence the immune system.The inference of these findings are that first,changes in RCT and HDL functionality are as important,if not more so,than its changes in concentration,and second,that these changes are independent of each other.Thus,"HDL therapy" must consider alterations in RCT and HDL functionality as a result of the treatment and the implications that these changes have on the overall atheroprotective effect of the treatment.展开更多
文摘The atheroprotective effect of HDL is well-established, the implication being that the higher the plasma levels of HDL,the bigger the benefit to all individuals.Such a supposition has led to the development of "HDL therapy".It has fast become apparent however that assuming therapeutic benefits by merely raising HDL levels is highly simplistic.The most established atheroprotective function of HDL is its role in reverse cholesterol transport(RCT). However other functions of HDL not directly related to RCT may also contribute significantly to its atheioprotective properties.As well,there are many examples where the functionality of HDL changes discordantly to its concentration such that high levels of HDL can be pro-rather than antiatherogenic under certain metabolic conditions.In humans,the ability of HDL to support cholesterol efflux and maintain endothelial function,or antioxidant function can be diminished despite higher HDL levels.Conversely, apoA-IMilano mutation leads to lower HDL levels,but enhances HDL functionality.We and others have recently shown that HDL also has potent anti-inflammatory actions and can also influence the immune system.The inference of these findings are that first,changes in RCT and HDL functionality are as important,if not more so,than its changes in concentration,and second,that these changes are independent of each other.Thus,"HDL therapy" must consider alterations in RCT and HDL functionality as a result of the treatment and the implications that these changes have on the overall atheroprotective effect of the treatment.
