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 antiinflammatory 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.
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IntroductionThere have been several sharp turns in the evidence trail marking the atheroprotective role of high density lipoproteins (HDLs). Very early studies on dyslipidaemia highlighted the positive correlation between total triglycerides (TGs) with the risk of developing cardiovascular disease (CVD). Since the mid-1970s, numerous epidemiological and animal studies, including the Framingham Study (Gordon et al., 1977), reported that HDL cholesterol (HDL-C) has the strongest inverse relationship with the development of CVD of the known serum lipid factors (Badimon et al., 1990;Rubin et al., 1991;Liu et al., 1994;Plump et al., 1994). This association is underpinned by reverse cholesterol transport (RCT) -a process by which HDL-C transfers the cholesterol from peripheral cells, for example, lipid-laden foam cells, to the liver for secretion into bile and faeces. The promotion of RCT is considered a major anti-atherogenic function of HDL-C (Gofman et al., 1966;Miller and Miller, 1975;Rhoads et al., 1976). Based on these findings, interventions to increase the levels of HDL-C were developed but found to be ineffective for preventing cardiovascular outcomes in several large clinical trials (Brousseau et al., 2004;McKenney et al., 2006;Barter et al., 2007;Boden et al., 2011;Lü...
