The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 7 No.
4 • September 2004
HDL: Not Always “Good” Cholesterol
Recent reports explain how HDL can, under certain conditions, be converted from a protective anti-inflammatory type of cholesterol to a pro-inflammatory type, which may help explain why some people with normal HDL levels still have heart attacks.
In an early study, researchers found that HDL becomes inflammatory during the acute phase response (APR), which is a systemic reaction to infectious and noninfectious tissue-destructive processes. In rabbits, the protective effects of HDL rapidly declined during the APR, until by the third day these effects were completely lost. The level of Apo A-1, the primary protein constituent of HDL, was reduced by 73%, while the levels of paraoxonase (which destroys organic peroxides) and platelet activating factor acetylhydrolase (two enzyme systems associated with HDL) declined by 71% and 90%, respectively. Infecting mice with influenza reduced the ability of HDL to inhibit LDL oxidation and LDL-induced monocyte chemotactic activity in human artery cell-wall cocultures, resulting in the loss of HDL’s anti-inflammatory properties.
A new study now shows that an inflammatory enzyme, myeloperoxidase, selectively targets apolipoprotein A-1 (Apo A-1), which in turn eliminates the anti-inflammatory effects of HDL. The authors of this study report that in cardiovascular disease patients or in those with diabetes, HDL is actually proinflammatory as compared to HDL in normal individuals. The myeloperoxidase-catalyzed oxidation, chlorination, and nitration of HDL and Apo A-1 result in the loss of the ability of HDL to remove cholesterol from macrophages.
Short-term (acute-phase) changes in HDL are probably normal parts of the immune response. However, these results suggest that chronic inflammatory states such as occur in cardiovascular disease and diabetes have a negative impact on the protective effects of HDL. Under these circumstances, HDL is no longer “good” cholesterol.
- Van Lenten et al. Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. J Clin Investig 96:2758-67 (1995).
- Van Lenten et al. High-density lipoprotein loses its anti-inflammatory properties during acute influenza A infection. Circulation 103:2283-8 (2001).
- Fogelman. When good cholesterol goes bad. Nature Med 10(9):902-3 (2004).
- Service. Enzyme deactivates heart-friendly HDL. Science 305:1558-9 (2004).
- Zheng et al. Apolipoprotein A-1 is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular disease. J Clin Investig 114(4):529-41 (2004).