HDL quality and functionality: what can proteins and genes predict?

Abstract

Epidemiological and clinical studies have over the years established that dyslipidemia constitutes the main risk factor for atherosclerosis. The inverse correlation between HDL cholesterol (HDL-C) levels and coronary heart disease morbidity and mortality identified HDL-C as an alternative pharmacological target to LDL-C and a potential anti-atherosclerosis marker. However, more recent data reinforced the principle of 'HDL quality' in atherosclerosis that refers to the functionality of HDL particle, as defined by its protein and lipid content, rather than HDL-C levels in plasma. Since HDL functionality depends on the genes and proteins of the HDL metabolic pathway, its apoprotein composition may serve as a surrogate marker of atheroprotection. In this manuscript we review the atheroprotective properties of HDL in relation to the proteins of HDL metabolic pathway and discuss what HDL-associated genes and proteins may reveal about HDL functionality in the assessment of coronary risk.

Apolipoprotein CIII and diabetes. Is there a link?

“…Intriguingly, although the main clinical variable used to assess HDL is HDL‐cholesterol level, this parameter fails to provide information concerning the quality and function of the HDL particles. The apolipoprotein composition of HDL, however, might be more informative in explaining HDL function . It is of high interest that HDL particles are highly heterogeneous regarding apolipoprotein content.…”

“…The apolipoprotein composition of HDL, however, might be more informative in explaining HDL function. 83,84 It is of high interest that HDL particles are highly heterogeneous regarding apolipoprotein content. For instance, concerning ApoCIII, it is present in 4% of HDL particles in normal weight individuals, whereas in 10% of HDL particles in obese subjects.…”

High-density lipoprotein (HDL) metabolism and bone mass

“…1954, Havel et al . 1955, Miller et al 1975, Tsompanidi et al 2010, Kypreos et al 2013, Karavia et al . 2014), suggested that high HDL-C levels in plasma are protective against the development of atherosclerosis.…”

“…As a result, the majority of studies in the literature focused on the understanding of HDL-C levels in human pathology, a simplified approach to HDL that dates back to the early days when little was known about HDL structure and function. However, more recent data from experimental mice and clinical trials indicated that HDL particle functionality, as determined by its apolipoprotein (apo) and lipid content, is far more important in atheroprotection than HDL-C levels alone (Tsompanidi et al 2010, Karavia et al . 2014, Constantinou et al .…”

“…Though HDL was originally brought under the spotlight due its importance in protection from atherosclerosis, more recent findings propose a multifunctional role of HDL in numerous other biological processes including, inflammation, oxidative stress, nitric oxide production, and regulation of plasma glucose homeostasis (Karavia et al 2014). In addition to atherosclerosis and coronary heart disease, recent data indicate that HDL may play pivotal role in the pathology and treatment of other diseases including morbid obesity, nonalcoholic fatty liver disease, type 2 diabetes mellitus, obstructive pulmonary disease, and numerous diseases of the central nervous system (Constantinou et al 2015).…”