Abstract 035: Recombinant LCAT Restores Defective HDL mediated Endothelial Protection in Acute Coronary Syndrome

Abstract

Recent evidence suggests that the vasoprotective effects of HDL are impaired in patients during an acute coronary syndrome (ACS). In particular, HDL from ACS patients are defective in promoting nitric oxide (NO) release from cultured endothelial cells (ECs). Lecithin:cholesterol acyltransferase (LCAT) plays a key role in HDL maturation and remodeling, and it is the enzyme responsible for cholesterol esterification in plasma. Very few studies have suggested that LCAT activity is decreased during an acute myocardial infarction, but the possible link between LCAT mass/activity and the HDL dysfunction observed in ACS has never been tested. To test this hypothesis, plasma from 30 STEMI patients was collected at admission, 48 and 72 hours and 30 days after event. LCAT concentration and activity significantly decreased 48 hours after event (-0.49±0.11 μg/ml, P<0.001, and -3.15±1.05 nmol/ml/h, P=0.006) and remained reduced at 72 hours. HDL isolated from STEMI patients lose the capacity to promote NO production in ECs (-0.13 ± 0.06 fold, P=0.04) and the reduction is significantly correlated to decreased LCAT activity (R= 0.52, P=0.003). In vitro studies were performed in which STEMI patients’ plasma was added with rhLCAT and HDL vasoprotective activity assessed by measuring NO production in ECs. In vitro incubation of STEMI patients’ plasma with rhLCAT remodels phospholipids and protein content in HDL and restores HDL ability to promote endothelial NO production (+25%, P=0.03). Impairment of cholesterol esterification may be a major factor in the HDL dysfunction observed during ACS. rhLCAT is able to restore HDL-mediated NO production in vitro, suggesting LCAT as potential therapeutic target for restoring HDL functionality in ACS.