Faculty Collaboration Database

Recombinant LCAT (Lecithin:Cholesterol Acyltransferase) Rescues Defective HDL (High-Density Lipoprotein)-Mediated Endothelial Protection in Acute Coronary Syndrome. Arterioscler Thromb Vasc Biol 2019 May;39(5):915-924

Date

03/22/2019

Pubmed ID

30894011

DOI

10.1161/ATVBAHA.118.311987

Scopus ID

2-s2.0-85065216772 (requires institutional sign-in at Scopus site)   41 Citations

Abstract

Objective- Aim of this study was to evaluate changes in LCAT (lecithin:cholesterol acyltransferase) concentration and activity in patients with an acute coronary syndrome, to investigate if these changes are related to the compromised capacity of HDL (high-density lipoprotein) to promote endothelial nitric oxide (NO) production, and to assess if rhLCAT (recombinant human LCAT) can rescue the defective vasoprotective HDL function. Approach and Results- Thirty ST-segment-elevation myocardial infarction (STEMI) patients were enrolled, and plasma was collected at hospital admission, 48 and 72 hours thereafter, at hospital discharge, and at 30-day follow-up. Plasma LCAT concentration and activity were measured and related to the capacity of HDL to promote NO production in cultured endothelial cells. In vitro studies were performed in which STEMI patients' plasma was added with rhLCAT and HDL vasoprotective activity assessed by measuring NO production in endothelial cells. The plasma concentration of the LCAT enzyme significantly decreases during STEMI with a parallel significant reduction in LCAT activity. HDL isolated from STEMI patients progressively lose the capacity to promote NO production by endothelial cells, and the reduction is related to decreased LCAT concentration. In vitro incubation of STEMI patients' plasma with rhLCAT restores HDL ability to promote endothelial NO production, possibly related to significant modification in HDL phospholipid classes. Conclusions- Impairment of cholesterol esterification may be a major factor in the HDL dysfunction observed during acute coronary syndrome. rhLCAT is able to restore HDL-mediated NO production in vitro, suggesting LCAT as potential therapeutic target for restoring HDL functionality in acute coronary syndrome.

Author List

Ossoli A, Simonelli S, Varrenti M, Morici N, Oliva F, Stucchi M, Gomaraschi M, Strazzella A, Arnaboldi L, Thomas MJ, Sorci-Thomas MG, Corsini A, Veglia F, Franceschini G, Karathanasis SK, Calabresi L

Authors

Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of Wisconsin
Michael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Coronary Syndrome
Biomarkers
Cohort Studies
Female
Humans
Lipoproteins, HDL
Male
Nitric Oxide
Phosphatidylcholine-Sterol O-Acyltransferase
Prognosis
ST Elevation Myocardial Infarction
Sensitivity and Specificity
Sterol O-Acyltransferase