title: Recombinant human LCAT normalizes plasma lipoprotein profile in LCAT deficiency.
abstract: Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for cholesterol esterification in plasma. Mutations in the LCAT gene leads to two rare disorders, familial LCAT deficiency and fish-eye disease, both characterized by severe hypoalphalipoproteinemia associated with several lipoprotein abnormalities. No specific treatment is presently available for genetic LCAT deficiency. In the present study, recombinant human LCAT was expressed and tested for its ability to correct the lipoprotein profile in LCAT deficient plasma. The results show that rhLCAT efficiently reduces the amount of unesterified cholesterol (-30%) and promotes the production of plasma cholesteryl esters (+210%) in LCAT deficient plasma. rhLCAT induces a marked increase in HDL-C levels (+89%) and induces the maturation of small preβ-HDL into alpha-migrating particles. Moreover, the abnormal phospholipid-rich particles migrating in the LDL region were converted in normally sized LDL.
authors.affiliation: Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Simonelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Tinti
authors.forename: Laura
authors.initials: L
authors.lastname: Salvini
authors.forename: Laura
authors.initials: L
authors.lastname: Tinti
authors.forename: Alice
authors.initials: A
authors.lastname: Ossoli
authors.forename: Cecilia
authors.initials: C
authors.lastname: Vitali
authors.forename: Vitor
authors.initials: V
authors.lastname: Sousa
authors.forename: Gaetano
authors.initials: G
authors.lastname: Orsini
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Nolli
authors.forename: Guido
authors.initials: G
authors.lastname: Franceschini
authors.forename: Laura
authors.initials: L
authors.lastname: Calabresi
mesh_terms: D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D005192:Family Health; D057809:HEK293 Cells; D006801:Humans; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000097:blood* / Q000235:genetics; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism; D009154:Mutation; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000097:blood* / Q000378:metabolism
chemical_list: D008074:Lipoproteins; D011994:Recombinant Proteins; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase
keywords: CE; FED; FLD; FPLC; Familial LCAT deficiency; HDL; LCAT; Lipoproteins; apoA-I; apolipoprotein A-I; cholesteryl esters; familial LCAT deficiency; fast performance liquid chromatography; fish-eye disease; lecithin:cholesterol acyltransferase