HDL levels and oxidizability during myocardial infarction are associated with reduced endothelial-mediated vasodilation and nitric oxide bioavailability

•During STEMI, high plasma HDL-C levels were associated with endothelial dysfunction.•Acute inflammatory response elicits dynamic structural and functional changes in HDL.•Apo A-I content is decreased, and anti-oxidant/inflammatory capacity are impaired.•HDL becomes more prone to oxidation and the gathering of TBARS into HDL is enhanced.•The magnitude of HDL oxidation was negatively correlated with endothelial function.

ObjectiveAcute phase response modifies high-density lipoprotein (HDL) into a dysfunctional particle that may favor oxidative/inflammatory stress and eNOS dysfunction. The present study investigated the impact of this phenomenon on patients presenting ST-elevation myocardial infarction (STEMI).MethodsPlasma was obtained from 180 consecutive patients within the first 24-h of onset of STEMI symptoms (D1) and after 5 days (D5). Nitrate/nitrite (NOx) and lipoproteins were isolated by gradient ultracentrifugation. The oxidizability of low-density lipoprotein incubated with HDL (HDLaoxLDL) and the HDL self-oxidizability (HDLautox) were measured after CuSO4 co-incubation. Anti-inflammatory activity of HDL was estimated by VCAM-1 secretion by human umbilical vein endothelial cells after incubation with TNF-α. Flow-mediated dilation (FMD) was assessed at the 30th day (D30) after STEMI.ResultsAmong patients in the first tertile of admission HDL-Cholesterol (<33 mg/dL), the increment of NOx from D1 to D5 [6.7(2; 13) vs. 3.2(-3; 10) vs. 3.5(-3; 12); p = 0.001] and the FMD adjusted for multiple covariates [8.4(5; 11) vs 6.1(3; 10) vs. 5.2(3; 10); p = 0.001] were higher than in those in the second (33-42 mg/dL) or third (>42 mg/dL) tertiles, respectively. From D1 to D5, there was a decrease in HDL size (−6.3 ± 0.3%; p < 0.001) and particle number (−22.0 ± 0.6%; p < 0.001) as well as an increase in both HDLaoxLDL (33%(23); p < 0.001) and HDLautox (65%(25); p < 0.001). VCAM-1 secretion after TNF-a stimulation was reduced after co-incubation with HDL from healthy volunteers (−24%(33); p = 0.009), from MI patients at D1 (−23%(37); p = 0.015) and at D30 (−22%(24); p = 0.042) but not at D5 (p = 0.28).ConclusionDuring STEMI, high HDL-cholesterol is associated with a greater decline in endothelial function. In parallel, structural and functional changes in HDL occur reducing its anti-inflammatory and anti-oxidant properties.