Current and future therapies for addressing the effects of inflammation on HDL cholesterol metabolism.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Inflammatory processes arising from metabolic abnormalities are known to precipitate the development of CVD. Several metabolic and inflammatory markers have been proposed for predicting the progression of CVD, including high density lipoprotein cholesterol (HDL-C). For ~50 years, HDL-C has been considered as the atheroprotective 'good' cholesterol because of its strong inverse association with the progression of CVD. Thus, interventions to increase the concentration of HDL-C have been successfully tested in animals; however, clinical trials were unable to confirm the cardiovascular benefits of pharmaceutical interventions aimed at increasing HDL-C levels. Based on these data, the significance of HDL-C in the prevention of CVD has been called into question. Fundamental in vitro and animal studies suggest that HDL-C functionality, rather than HDL-C concentration, is important for the CVD-preventive qualities of HDL-C. Our current review of the literature positively demonstrates the negative impact of systemic and tissue (i.e. adipose tissue) inflammation in the healthy metabolism and function of HDL-C. Our survey indicates that HDL-C may be a good marker of adipose tissue health, independently of its atheroprotective associations. We summarize the current findings on the use of anti-inflammatory drugs to either prevent HDL-C clearance or improve the function and production of HDL-C particles. It is evident that the therapeutic agents currently available may not provide the optimal strategy for altering HDL-C metabolism and function, and thus, further research is required to supplement this mechanistic approach for preventing the progression of CVD. LINKED ARTICLES: This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc.