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Pleiotropic effects of HDL: towards new therapeutic areas for HDL-targeted interventions

S C Gordts, N Singh, I Muthuramu

  • 1Centre for Molecular and Vascular Biology, Department of Cardiovascular Medicine, Catholic University of Leuven, Campus Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. bart.degeest@med.kuleuven.be.

Current Molecular Medicine
|November 19, 2013
PubMed

Insights

High-density lipoprotein (HDL) cholesterol

Area of Science:

  • Cardiovascular Medicine and Therapeutics
  • Lipid Metabolism and Atherosclerosis Research

Background:

  • Plasma levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I show an inverse correlation with coronary heart disease (CHD) incidence.
  • The HDL hypothesis posits that increasing HDL cholesterol reduces CHD risk, but recent trials have yielded inconclusive results.
  • Mendelian randomization studies suggest potential residual confounding in the epidemiological link between HDL cholesterol and coronary artery disease.

Purpose of the Study:

  • To re-evaluate the HDL hypothesis in light of recent clinical trial outcomes and ongoing research.
  • To explore the pleiotropic functions of HDL beyond reverse cholesterol transport.
  • To identify and present novel therapeutic areas for HDL-targeted interventions.

Main Methods:

  • Review of existing clinical trial data and epidemiological studies on HDL cholesterol and cardiovascular disease.
  • Analysis of Mendelian randomization studies investigating HDL-C and coronary artery disease.
  • Synthesis of pre-clinical and clinical data supporting novel therapeutic applications of HDL.

Main Results:

  • Recent HDL trials' lack of positive clinical outcomes may stem from poor HDL specificity of investigated drugs.
  • HDL possesses diverse functions including anti-inflammatory, anti-oxidative, and endothelial protective effects.
  • Four promising new therapeutic areas for HDL-targeted diseases have been identified.

Conclusions:

  • The clinical utility of raising HDL cholesterol for CHD prevention requires further investigation, considering drug specificity and potential confounding factors.
  • HDL's pleiotropic effects offer potential for therapeutic applications beyond traditional cardiovascular risk reduction.
  • Critical illness, allograft vasculopathy, type 2 diabetes mellitus, and heart failure represent strategic new frontiers for HDL-targeted therapies.

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