190 - LIPA gene mutations affect the composition of lipoproteins: enrichment in ACAT-derived cholesteryl esters (ID 355)
- Monica Gomaraschi, Italy
- Lorenzo Arnaboldi, Italy
- Alice Ossoli, Italy
- Eleonora Giorgio, Italy
- Livia Pisciotta, Italy
- Tiziano Lucchi, Italy
- Liliana Grigore, Italy
- Chiara Pavanello, Italy
- Agnese Granata, Italy
- Andrea Pasta, Italy
- Beatrice Arosio, Italy
- Domenico Azzolino, Italy
- Andrea Baragetti, Italy
- Alberto Corsini, Italy
- Alberico Luigi Catapano, Italy
- Laura Calabresi, Italy
Abstract
Background and Aims
Patients with cholesteryl ester storage disease (CESD) are exposed to an increased cardiovascular risk, due to hepatic steatosis, hypercholesterolemia and hypoalphalipoproteinemia. Further insights into the impact of the disease on lipid/lipoprotein metabolism are limited. Aim of the study was to investigate the effect of carrying one or two mutant LIPA alleles on lipoprotein composition and function.
Methods
Lipoproteins were isolated from 6 CESD patients, 5 heterozygous relatives (carriers) and 12 sex/age matched controls. Lipoprotein mass composition and the fatty acid distribution of cholesteryl esters (CEs) were assessed. HDL function was evaluated as nitric oxide release by HDL-stimulated endothelial cells. Cardiovascular status was investigated by carotid IMT.
Results
Despite the lipid-lowering therapy, total and LDL-cholesterol were increased in CESD patients and carriers compared to controls; HDL-cholesterol was reduced in CESD. Very low and intermediate density lipoproteins from CESD patients and carriers were enriched in CEs compared to the control ones, with a concomitant reduction of triglycerides. In addition, CEs in serum and lipoproteins of CESD patients were depleted in linoleate, due to a reduced LCAT activity. In CESD HDL, fatty acid distribution of CEs was shifted towards saturated ones, if compared to control HDL; however, these changes did not affect HDL ability to promote nitric oxide release by endothelial cells. Carotid IMT was increased in CESD patients compared to age/sex matched controls.
Conclusions
LIPA gene mutations significantly affected plasma levels and lipid composition of lipoproteins, likely contributing to the increased cardiovascular risk of affected patients.
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