"HDL : What a wonderful world"

12th February, 2016, 10:00-11:00,

Conference Room of RMSB Laboratory

A conference by Dr Anatol Kontush, Inserm research Unit 1166, University Pierre and Marie Curie, Pitie-Salpetriere Hospital, Paris

Contact: Gisele Clofent Sanchez, RMSB, gisele.clofent-sanchez@u-bordeaux.fr

For longer than 20 years low circulating levels of cholesterol carried by high-density lipoprotein (HDL) are established to constitute a significant and independent predictor of cardiovascular disease. This discovery has generated considerable interest to HDL and resulted in the development of several therapeutic approaches to raise HDL-cholesterol (HDL-C) levels. Unexpectedly, the attempts to decrease cardiovascular risk by HDL-C raising largely failed, creating a major controversy in the field. In parallel, Mendelian randomization studies revealed that HDL-C concentrations are not necessarily related causatively to cardiovascular disease and may represent a biomarker of other metabolic pathways.

The negative outcomes of HDL-C-raising trials reflect high complexity of HDL metabolism, composition and structure. Plasma (HDL) is a small, dense and protein-rich lipoprotein as compared to other lipoprotein classes. HDL particles can be discoid or spherical, contain apolipoproteins, enzymes, acute-phase proteins, complement proteins, antiproteases and multiple lipid classes, and are highly heterogeneous in their properties. HDL metabolism is based on the dynamic nature of the apolipoprotein (apo) A-I, the major HDL protein, and ensures the processes of cellular cholesterol efflux and, in part, reverse cholesterol transport (RCT). In addition, HDL particles display several other atheroprotective activities, including anti-inflammatory, antioxidative, anti-apoptotic, anti-thrombotic, anti-infectious and anti-diabetic actions. Such multitude of biological activities undoubtedly reflects the complex composition of HDL; however, our knowledge of molecular mechanisms and compositional determinants of atheroprotective functions of HDL is far from complete.

Importantly, metabolism, composition and biological functions of HDL are compromised in several metabolic states associated with elevated cardiovascular risk, opening a window for novel therapeutic options. Nevertheless, direct physiopathological relevance of altered HDL metabolism and function is still lacking, indicating that despite several decades of intense research, further studies are still required to bring more light into the wonderful world of HDL particles. New research needs to unambiguously link HDL biology to cardiovascular disease and to finally develop long-awaited HDL-targeting treatment for this major health issue.