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

Abstract

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. LINKED ARTICLES 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...

Capsaicin Supplementation Improved Risk Factors of Coronary Heart Disease in Individuals with Low HDL-C Levels

“…This result was consistent with previous studies [ 6 ]. In general, inflammation is related to HDL-C metabolism [ 13 ]. We assumed that the beneficial effects of capsaicin supplementation on HDL-C levels and PLTP activity may be associated with its anti-inflammatory effect.…”

“…Cholesterylester transfer protein (CETP), phospholipid transfer protein (PLTP), and lecithin cholesterol acyltransferase (LCAT) are considered to play important roles in HDL-C metabolism and function in the process of atherogenesis [ 11 , 12 ]. Additionally, inflammation is generally associated with HDL-C metabolism [ 13 ]. Therefore, capsaicin may alter HDL-C through its effects on the above proteins and inflammation.…”

Probiotic Lactobacillus gasseri SBT2055 improves insulin secretion in a diabetic rat model

“…Similarly, dietary LG2055 has been reported to decrease postprandial free fatty acid levels in a human intervention study (Ogawa et al, 2014). Inflammation can decrease HDL cholesterol levels and attenuate HDL functionality (Iqbal et al, 2017). On the other hand, HDL particles alone can improve the inflammatory status (Navab et al, 2011).…”

Sex‐dependent difference in the relationship between adipose‐tissue cholesterol efflux and estradiol concentrations in young healthy humans

“…Although, we have studied a small number of men and women, the current data in conjunction with our previous work (Tuvdendorj et al, 2016) strongly suggests that this association is sex‐dependent. The role of AT in preventing the development of T2D, and atherosclerotic CVD in humans is well accepted (Tuvdendorj et al, 2013; Iqbal et al, 2017); however, the mechanisms underlying the sex‐dependent variabilities are not well understood. Because T2D and atherosclerotic CVD are risk factors for the development of vascular dementia, it is feasible that AT health plays a significant role in progression of vascular dementia.…”