Competitive inhibition of LDL binding and uptake by HDL in aortic endothelial cells

Alexander, Robert R.; Miguel, Remedios; Graham, Debra J.

doi:10.1016/0022-4804(90)90128-o

Cited by 9 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cholesterol intake from HDL by cultured cells occurred even in the presence of LDL up to 20 times the physiological concentration of LDL; this result was unexpected because LDL have been considered as the most important donor of cholesterol for peripheral cells [ 25 ]. The fact that cells preferred cholesterol from HDL rather than from LDL is in agreement with earlier studies, which demonstrated that HDL inhibited LDL uptake by bovine endothelial cells [ 26 , 27 ]. This suggests that HDL cholesterol has an important role in endothelial cell function.…”

Section: Discussionsupporting

confidence: 91%

HDL-Mediated Lipid Influx to Endothelial Cells Contributes to Regulating Intercellular Adhesion Molecule (ICAM)-1 Expression and eNOS Phosphorylation

Muñoz-Vega

Massó

Páez

et al. 2018

IJMS

View full text Add to dashboard Cite

Reverse cholesterol transport (RCT) is considered as the most important antiatherogenic role of high-density lipoproteins (HDL), but interventions based on RCT have failed to reduce the risk of coronary heart disease. In contrast to RCT, important evidence suggests that HDL deliver lipids to peripheral cells. Therefore, in this paper, we investigated whether HDL could improve endothelial function by delivering lipids to the cells. Internalization kinetics using cholesterol and apolipoprotein (apo) AI fluorescent double-labeled reconstituted HDL (rHDL), and human dermal microvascular endothelial cells-1 (HMEC-1) showed a fast cholesterol influx (10 min) and a slower HDL protein internalization as determined by confocal microscopy and flow cytometry. Sphingomyelin kinetics overlapped that of apo AI, indicating that only cholesterol became dissociated from rHDL during internalization. rHDL apo AI internalization was scavenger receptor class B type I (SR-BI)-dependent, whereas HDL cholesterol influx was independent of SR-BI and was not completely inhibited by the presence of low-density lipoproteins (LDL). HDL sphingomyelin was fundamental for intercellular adhesion molecule-1 (ICAM-1) downregulation in HMEC-1. However, vascular cell adhesion protein-1 (VCAM-1) was not inhibited by rHDL, suggesting that components such as apolipoproteins other than apo AI participate in HDL’s regulation of this adhesion molecule. rHDL also induced endothelial nitric oxide synthase eNOS S1177 phosphorylation in HMEC-1 but only when the particle contained sphingomyelin. In conclusion, the internalization of HDL implies the dissociation of lipoprotein components and a SR-BI-independent fast delivery of cholesterol to endothelial cells. HDL internalization had functional implications that were mainly dependent on sphingomyelin. These results suggest a new role of HDL as lipid vectors to the cells, which could be congruent with the antiatherogenic properties of these lipoproteins.

show abstract

Section: Discussionsupporting

confidence: 91%

HDL-Mediated Lipid Influx to Endothelial Cells Contributes to Regulating Intercellular Adhesion Molecule (ICAM)-1 Expression and eNOS Phosphorylation

Muñoz-Vega

Massó

Páez

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…These results suggest that the extrahepatic cells can take up cholesterol from HDL rather than from LDL (which requires the presence of ApoB receptors). They are consistent with earlier studies demonstrating that HDL inhibited LDL uptake by bovine endothelial cells [64,68,69]. Besides cholesterol, HDL delivers sphingomyelin to endothelial cells in culture, which mediates eNOS activation via phosphorylation and ICAM-1 expression [67].…”

Section: Hdl As Lipid Vectorssupporting

confidence: 92%

HDL as Bidirectional Lipid Vectors: Time for New Paradigms

Luna-Luna

Niesor²,

Pérez-Méndez

2022

Biomedicines

View full text Add to dashboard Cite

The anti-atherogenic properties of high-density lipoproteins (HDL) have been explained mainly by reverse cholesterol transport (RCT) from peripheral tissues to the liver. The RCT seems to agree with most of the negative epidemiological correlations between HDL cholesterol levels and coronary artery disease. However, therapies designed to increase HDL cholesterol failed to reduce cardiovascular risk, despite their capacity to improve cholesterol efflux, the first stage of RCT. Therefore, the cardioprotective role of HDL may not be explained by RCT, and it is time for new paradigms about the physiological function of these lipoproteins. It should be considered that the main HDL apolipoprotein, apo AI, has been highly conserved throughout evolution. Consequently, these lipoproteins play an essential physiological role beyond their capacity to protect against atherosclerosis. We propose HDL as bidirectional lipid vectors carrying lipids from and to tissues according to their local context. Lipid influx mediated by HDL appears to be particularly important for tissue repair right on site where the damage occurs, including arteries during the first stages of atherosclerosis. In contrast, the HDL-lipid efflux is relevant for secretory cells where the fusion of intracellular vesicles drastically enlarges the cytoplasmic membrane with the potential consequence of impairment of cell function. In such circumstances, HDL could deliver some functional lipids and pick up not only cholesterol but an integral part of the membrane in excess, restoring the viability of the secretory cells. This hypothesis is congruent with the beneficial effects of HDL against atherosclerosis as well as with their capacity to induce insulin secretion and merits experimental exploration.

show abstract

“…Most of the studies performed have involved the binding of lipoproteins to receptors located on cell membranes, and have been aimed at a better understanding of the binding characteristics of LDL and HDL to their receptors (34)(35)(36). HDL has been found to inhibit atherogenesis by regulating the binding of LDL to cell receptor molecules (37). It has been observed that the means of inhibition is through competitive binding or steric hindrance of LDL by HDL, suggesting a common basis of HDL and LDL binding to the cell surface.…”

Section: Application Of Protein Adsorption Analysis By Ir Spectroscopymentioning

confidence: 99%

“…As mentioned above, adsorption of proteins has been investigated in the past, but several questions on various aspects of the adhesion process remain unanswered. Previous studies have only involved isolated proteins without consideration of the presence of other macromolecules in the surrounding (37,38). Role of the surrounding media in the protein adsorption is especially applicable to HDL and LDL, where proteins are always tightly surrounded by lipids.…”

Section: Application Of Protein Adsorption Analysis By Ir Spectroscopymentioning

confidence: 99%

“…This problem has not been solved in the past, because of the signal interference of other macromolecules in the study of the protein adsorption. Infra-red spectroscopy has successfully been used to quantitate adsorbed proteins (5,18,37,38) and to estimate the secondary structure of proteins (39)(40)(41). In particular, FT-IR in combination with ATR has been utilized to characterize adsorbed proteins (5,18,42).…”

Section: Application Of Protein Adsorption Analysis By Ir Spectroscopymentioning

confidence: 99%

See 1 more Smart Citation

Basic Aspects of the Technique and Applications of Infrared Spectroscopy of Peptides and Proteins

Singh

1999

ACS Symposium Series

105

106

View full text Add to dashboard Cite

Infrared spectroscopy is being increasingly utilized for the analysis of peptides and proteins because it probes the universally available amide (peptide) bonds, which display distinct IR signals for differently folded peptides and proteins. Other spectroscopic techniques useful for studying protein structures in solutions are circular dichroism (CD), ultraviolet absorption and fluorescence spectroscopy, Raman and nuclear magnetic resonance (NMR). Among the techniques for secondary structure, NMR and Raman spectroscopy need unusually high concentration of proteins, and NMR analysis is still limited to small proteins of about 200 amino acid residues. CD analysis is limited to clear protein solution (as opposed to membrane proteins) due to the problem with light scattering. Furthermore, for estimation of secondary structure of protein by CD accurate protein concentration is needed. Infrared spectroscopy is an emerging technique for protein analysis. Amide I, II and III are most commonly used IR spectral regions used for protein structure-function analysis. Recent advances in the development of instrumentation (Fourier transformation, sampling), protein IR data bank (band assignments to different components of secondary structure), and techniques (two-dimensional IR methods, time-resolution, and isotopic labeling) have significantly augmented IR spectroscopy as an analytical tool for peptides and proteins. This chapter provides an overview of the basic technique and some of the applications of IR spectroscopy to examine structure, interaction, and conformational changes in peptides and proteins.

show abstract

Competitive inhibition of LDL binding and uptake by HDL in aortic endothelial cells

Cited by 9 publications

References 20 publications

HDL-Mediated Lipid Influx to Endothelial Cells Contributes to Regulating Intercellular Adhesion Molecule (ICAM)-1 Expression and eNOS Phosphorylation

HDL-Mediated Lipid Influx to Endothelial Cells Contributes to Regulating Intercellular Adhesion Molecule (ICAM)-1 Expression and eNOS Phosphorylation

HDL as Bidirectional Lipid Vectors: Time for New Paradigms

Basic Aspects of the Technique and Applications of Infrared Spectroscopy of Peptides and Proteins

Contact Info

Product

Resources

About