title: HDL levels and oxidizability during myocardial infarction are associated with reduced endothelial-mediated vasodilation and nitric oxide bioavailability.
abstract: Acute 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).
  
  
  
  Plasma 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 30(th) day (D30) after STEMI.
  
  
  
  Among 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).
  
  
  
  During 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.
authors.affiliation: Cardiology Division, Faculty of Medical Sciences, State University of Campinas (Unicamp), Campinas, SP, Brazil.
authors.forename: Luiz Sergio F
authors.initials: LS
authors.lastname: Carvalho
authors.affiliation: Cardiology Division, Faculty of Medical Sciences, State University of Campinas (Unicamp), Campinas, SP, Brazil.
authors.forename: Natália
authors.initials: N
authors.lastname: Panzoldo
authors.affiliation: Cardiology Division, Faculty of Medical Sciences, State University of Campinas (Unicamp), Campinas, SP, Brazil.
authors.forename: Simone N
authors.initials: SN
authors.lastname: Santos
authors.affiliation: Cardiology Division, Faculty of Medical Sciences, State University of Campinas (Unicamp), Campinas, SP, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Modolo
authors.affiliation: Cardiology Division, Faculty of Medical Sciences, State University of Campinas (Unicamp), Campinas, SP, Brazil.
authors.forename: Breno
authors.initials: B
authors.lastname: Almeida
authors.affiliation: Escola Superior de Ciencias da Saúde (ESCS), Brasilia, DF, Brazil.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Quinaglia E Silva
authors.affiliation: Cardiology Division, Faculty of Medical Sciences, State University of Campinas (Unicamp), Campinas, SP, Brazil.
authors.forename: Wilson
authors.initials: W
authors.lastname: Nadruz
authors.affiliation: Lipids Laboratory, Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, Sao Paulo, Brazil.
authors.forename: Eliana C
authors.initials: EC
authors.lastname: de Faria
authors.affiliation: Cardiology Division, Faculty of Medical Sciences, State University of Campinas (Unicamp), Campinas, SP, Brazil. Electronic address: andreisposito@gmail.com.
authors.forename: Andrei C
authors.initials: AC
authors.lastname: Sposito
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000737:chemistry; D019540:Area Under Curve; D001786:Blood Glucose / Q000737:chemistry; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006801:Humans; D007249:Inflammation; D008075:Lipoproteins, HDL / Q000097:blood*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D009569:Nitric Oxide / Q000737:chemistry*; D010100:Oxygen / Q000097:blood* / Q000737:chemistry; D010641:Phenotype; D011446:Prospective Studies; D017392:Thiobarbituric Acid Reactive Substances; D016896:Treatment Outcome; D014664:Vasodilation
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D008075:Lipoproteins, HDL; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D010100:Oxygen
keywords: Anti-inflammatory; Anti-oxidant; Endothelial dysfunction; Flow-mediated dilation; High-density lipoprotein; Myocardial infarction