Low Serum High Density Lipoprotein Cholesterol Concentration is an Independent Predictor for Enhanced Inflammation and Endothelial Activation

Abstract

BackgroundInflammation, endothelial activation and oxidative stress have been established as key events in the initiation and progression of atherosclerosis. High-density lipoprotein cholesterol (HDL-c) is protective against atherosclerosis and coronary heart disease, but its association with inflammation, endothelial activation and oxidative stress is not well established.Objectives(1) To compare the concentrations of biomarkers of inflammation, endothelial activation and oxidative stress in subjects with low HDL-c compared to normal HDL-c; (2) To examine the association and correlation between HDL-c and these biomarkers and (3) To determine whether HDL-c is an independent predictor of these biomarkers.Methods422 subjects (mean age±SD = 43.2±11.9years) of whom 207 had low HDL-c concentrations (HDL-c <1.0mmol/L and <1.3mmol/L for males and females respectively) and 215 normal controls (HDL-c ≥1.0 and ≥1.3mmol/L for males and females respectively) were recruited in this study. The groups were matched for age, gender, ethnicity, smoking status, diabetes mellitus and hypertension. Fasting blood samples were collected for analysis of biomarkers of inflammation [high-sensitivity C-reactive protein (hsCRP) and Interleukin-6 (IL-6)], endothelial activation [soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), soluble Intercellular Adhesion Molecule-1 (sICAM-1) and E-selectin)] and oxidative stress [F2-Isoprostanes, oxidized Low Density Lipoprotein (ox-LDL) and Malondialdehyde (MDA)].ResultsSubjects with low HDL-c had greater concentrations of inflammation, endothelial activation and oxidative stress biomarkers compared to controls. There were negative correlations between HDL-c concentration and biomarkers of inflammation (IL-6, p = 0.02), endothelial activation (sVCAM-1 and E-selectin, p = 0.029 and 0.002, respectively), and oxidative stress (MDA and F2-isoprostane, p = 0.036 and <0.0001, respectively). Multiple linear regression analysis showed HDL-c as an independent predictor of IL-6 (p = 0.02) and sVCAM-1 (p<0.03) after correcting for various confounding factors.ConclusionLow serum HDL-c concentration is strongly correlated with enhanced status of inflammation, endothelial activation and oxidative stress. It is also an independent predictor for enhanced inflammation and endothelial activation, which are pivotal in the pathogenesis of atherosclerosis and atherosclerosis-related complications.

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

“…Systemically, high HDL concentrations have been associated with decreased inflammatory cytokine levels and decreased systemic oxidative stress via associated antioxidant enzymes and by acting as acceptors of prooxidant lipids 13, 17, 18, 19, 20. In addition, high HDL concentrations are associated with decreased endothelial adhesion molecule expression, increased endothelial nitric oxide production, and decreased endothelial damage 14, 16, 17. Decreased HDL anti‐inflammatory, antioxidant, and endothelial protective capacities are associated with an increased risk of chronic kidney disease 32, 33, 34, 35.…”

“…13,[17][18][19][20] In addition, high HDL concentrations are associated with decreased endothelial adhesion molecule expression, increased endothelial nitric oxide production, and decreased endothelial damage. 14,16,17 Decreased HDL antiinflammatory, antioxidant, and endothelial protective capacities are associated with an increased risk of chronic kidney disease. [32][33][34][35] Each of these processes (systemic inflammation, oxidative stress, and endothelial dysfunction and damage) plays a key role in the pathogenesis of AKI.…”

“…High‐density lipoproteins (HDLs) have systemic anti‐inflammatory and antioxidant properties and limit endothelial dysfunction and damage by attenuating endothelial cell activation and adhesion molecule expression, by activating endothelial nitric oxide synthase, and by promoting endothelial repair 10, 13, 14, 15, 16, 17, 18, 19, 20. In critically ill patients with pneumonia or sepsis, low HDL cholesterol concentrations are associated with multiorgan dysfunction and short‐ and long‐term death 21, 22.…”

“…[7][8][9][10][11][12] High-density lipoproteins (HDLs) have systemic anti-inflammatory and antioxidant properties and limit endothelial dysfunction and damage by attenuating endothelial cell activation and adhesion molecule expression, by activating endothelial nitric oxide synthase, and by promoting endothelial repair. 10,[13][14][15][16][17][18][19][20] In critically ill patients with pneumonia or sepsis, low HDL cholesterol concentrations are associated with multiorgan dysfunction and short-and long-term death. 21,22 In a similar manner among cardiac surgery patients, a low HDL cholesterol concentration could increase the risk of organ dysfunction, including postoperative AKI, and conversely, a high concentration of HDL cholesterol could decrease the risk of postoperative AKI.…”

Effects of growth hormone therapy on metabolic parameters, adipokine and endothelial dysfunction in prepuberal children

“…In adult subjects with untreated growth hormone deficiency (GHD), their unfavourable lipid profiles put them at a higher risk of developing cardiovascular disease. They also tend to show elevated baseline insulin levels and increased insulin resistance (IR) .…”