Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Abstract

Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary heart disease. HDL mediates cholesterol efflux from macrophages for reverse transport to the liver and elicits many anti-inflammatory and anti-oxidative activities which are potentially antiatherogenic. Nevertheless, HDL has not been successfully targeted by drugs for prevention or treatment of cardiovascular diseases. One potential reason is the targeting of HDL cholesterol which does not capture the structural and functional complexity of HDL particles. Hundreds of lipid species and dozens of proteins as well as several microRNAs have been identified in HDL. This physiological heterogeneity is further increased in pathologic conditions due to additional quantitative and qualitative molecular changes of HDL components which have been associated with both loss of physiological function and gain of pathologic dysfunction. This structural and functional complexity of HDL has prevented clear assignments of molecules to the functions of normal HDL and dysfunctions of pathologic HDL. Systematic analyses of structure-function relationships of HDL-associated molecules and their modifications are needed to test the different components and functions of HDL for their relative contribution in the pathogenesis of atherosclerosis. The derived biomarkers and targets may eventually help to exploit HDL for treatment and diagnostics of cardiovascular diseases.

Reconstituted high density lipoprotein mediated targeted co-delivery of HZ08 and paclitaxel enhances the efficacy of paclitaxel in multidrug-resistant MCF-7 breast cancer cells

“…2(B)), which provided steric stabilization. This result was consistent with previously published studies (Annema and von Eckardstein, 2016;Kuai et al, 2016;Zhang et al, 2011b). Standard curves of PTX and HZ08 were linear over the concentration range from 0.1 to 60 μg/mL with a regression coeffiient of 0.999 (Table 1.).…”

HDL subfraction distribution and HDL function in untreated dyslipidemic patients

“…However, under particular circumstances, HDL particles may become dysfunctional caused by the loss of antioxidant and anti-inflammatory proteins in combination with a gain of acute phase proteins and some further proinflammatory components. This pro-inflammatory, dysfunctional HDL is unable to protect low-density lipoprotein (LDL) from oxidation and to prevent monocyte migration into the vessel wall induced by oxidized LDL particles [4] . Myeloperoxidase (MPO) mediates the oxidation of ApoA1 that creates a dysfunctional HDL particle, which activates nuclear factor kappa-B and promotes inflammation in the vessel wall [5] .…”

Novel Methods in Pulmonary Hypertension Phenotyping in the Age of Precision Medicine (2015 Grover Conference Series)

“…38,39 HDL-C protects against lipid oxidation, has anti-inflammatory properties, reduces endothelial dysfunction, and has anticoagulant effects. Low HDL-C levels are a prominent feature of the metabolic syndrome and insulin resistance.…”