TY - JOUR
T1 - Lipoprotein hydrophobic core lipids are partially extruded to surface in smaller HDL
T2 - "herniated" HDL, a common feature in diabetes
AU - Amigo, Nuria
AU - Mallol, Roger
AU - Heras, Mercedes
AU - Martinez-Hervas, Sergio
AU - Blanco-Vaca, Francisco
AU - Escola-Gil, Joan Carles
AU - Plana, Nuria
AU - Yanes, Oscar
AU - Masana, Lluis
AU - Correig, Xavier
N1 - Funding Information:
We thank the financial support from the Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), the Instituto de Investigación Carlos III (ISCIII) and the Spanish Ministry of Health and Consumption grant FIS 12-00291 (to J.C.E-G).
PY - 2016/1/18
Y1 - 2016/1/18
N2 - Recent studies have shown that pharmacological increases in HDL cholesterol concentrations do not necessarily translate into clinical benefits for patients, raising concerns about its predictive value for cardiovascular events. Here we hypothesize that the size-modulated lipid distribution within HDL particles is compromised in metabolic disorders that have abnormal HDL particle sizes, such as type 2 diabetes mellitus (DM2). By using NMR spectroscopy combined with a biochemical volumetric model we determined the size and spatial lipid distribution of HDL subclasses in a cohort of 26 controls and 29 DM2 patients before and after two drug treatments, one with niacin plus laropiprant and another with fenofibrate as an add-on to simvastatin. We further characterized the HDL surface properties using atomic force microscopy and fluorescent probes to show an abnormal lipid distribution within smaller HDL particles, a subclass particularly enriched in the DM2 patients. The reduction in the size, force cholesterol esters and triglycerides to emerge from the HDL core to the surface, making the outer surface of HDL more hydrophobic. Interestingly, pharmacological interventions had no effect on this undesired configuration, which may explain the lack of clinical benefits in DM2 subjects.
AB - Recent studies have shown that pharmacological increases in HDL cholesterol concentrations do not necessarily translate into clinical benefits for patients, raising concerns about its predictive value for cardiovascular events. Here we hypothesize that the size-modulated lipid distribution within HDL particles is compromised in metabolic disorders that have abnormal HDL particle sizes, such as type 2 diabetes mellitus (DM2). By using NMR spectroscopy combined with a biochemical volumetric model we determined the size and spatial lipid distribution of HDL subclasses in a cohort of 26 controls and 29 DM2 patients before and after two drug treatments, one with niacin plus laropiprant and another with fenofibrate as an add-on to simvastatin. We further characterized the HDL surface properties using atomic force microscopy and fluorescent probes to show an abnormal lipid distribution within smaller HDL particles, a subclass particularly enriched in the DM2 patients. The reduction in the size, force cholesterol esters and triglycerides to emerge from the HDL core to the surface, making the outer surface of HDL more hydrophobic. Interestingly, pharmacological interventions had no effect on this undesired configuration, which may explain the lack of clinical benefits in DM2 subjects.
UR - http://www.scopus.com/inward/record.url?scp=84954513616&partnerID=8YFLogxK
U2 - 10.1038/srep19249
DO - 10.1038/srep19249
M3 - Article
C2 - 26778677
AN - SCOPUS:84954513616
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 19249
ER -