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Further evidence that high-density lipoprotein is a chameleon-like lipoprotein.

Fogelman AM - Eur. Heart J. (2015)

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA afogelman@mednet.ucla.edu.

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Zewinger et al. studied 3310 patients undergoing coronary angiography in the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study and determined that serum amyloid A (SAA) concentrations predicted all-cause and cardiovascular mortality... Patients with low SAA levels and higher high-density lipoprotein (HDL) cholesterol levels had lower all-cause and cardiovascular mortality... In contrast, patients with high SAA levels and higher HDL cholesterol levels had increased all-cause and cardiovascular mortality... In the KORA S4 Study, 4261 participants were recruited; subjects with previous myocardial infarction (n = 77), stroke (n = 48) or with missing values for HDL cholesterol or SAA were excluded (n = 102) as well as those lost to follow-up (n = 7)... In these populations, HDL cholesterol levels did not predict outcomes, but higher levels of the calculated biologically ‘effective’ HDL cholesterol were associated with reduced risk for all-cause mortality as well as reduced cardiovascular endpoints... In vitro studies showed that SAA-supplemented HDL reduced endothelial nitric oxide (NO) production and increased endothelial production of reactive oxygen species, leading to the loss of the ability of the HDL to decrease adhesion of mononuclear cells to TNF-α-treated endothelial cells... The authors concluded that ‘SAA turned HDL into a pro-inflammatory particle’... Consistent with this hypothesis, Ansell et al. reported that subjects with high levels of HDL cholesterol with coronary heart disease had pro-inflammatory HDL, while normal subjects had anti-inflammatory HDL... Besler et al. demonstrated that HDL from patients with coronary artery disease lacked endothelial anti-inflammatory effects and did not stimulate endothelial repair because it failed to induce endothelial nitric oxide (eNOS) production... HDL taken from subjects with rheumatoid arthritis had impaired ability to stimulate cholesterol efflux... Charles-Schoenman et al. studied 36 patients with rheumatoid arthritis that were treated with tofacitinib (an oral Janus kinase inhibitor) for 6 weeks and found a trend toward lower SAA levels (51.93 ± 95.61 vs. 24.97 ± 48.96 mg/L; P = 0.0588) and HDL-associated SAA levels (34.76 ± 62.83 vs. 17.79 ± 34.45 mg/L; P = 0.0647), suggesting that resolution of inflammation decreases both plasma levels of SAA and levels of HDL-associated SAA.

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A schematic representation of the chameleon-like nature of HDL. In the non-inflammatory state, HDL contains little serum amyloid A (SAA) and promotes cholesterol efflux from macrophages, inhibits the production of reactive oxygen species (ROS) and increases nitric oxide (NO) production from endothelial cells. In the presence of an acute phase response or systemic inflammation the positive acute phase reactant SAA is produced by the liver and other tissues and associates with HDL. In the process of SAA associating with HDL, the HDL proteome is remodelled by reducing cardioprotective proteins associated with HDL. As a result, HDL-mediated cholesterol efflux is reduced, ROS production is stimulated and NO production is decreased, which leads to an enhancement of the inflammatory state.
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EHV465F1: A schematic representation of the chameleon-like nature of HDL. In the non-inflammatory state, HDL contains little serum amyloid A (SAA) and promotes cholesterol efflux from macrophages, inhibits the production of reactive oxygen species (ROS) and increases nitric oxide (NO) production from endothelial cells. In the presence of an acute phase response or systemic inflammation the positive acute phase reactant SAA is produced by the liver and other tissues and associates with HDL. In the process of SAA associating with HDL, the HDL proteome is remodelled by reducing cardioprotective proteins associated with HDL. As a result, HDL-mediated cholesterol efflux is reduced, ROS production is stimulated and NO production is decreased, which leads to an enhancement of the inflammatory state.

Mentions: The studies by Zewinger et al.1 as reported in this issue of the Journal provide further evidence of the chameleon-like nature of HDL. In the absence of an acute phase response or systemic inflammation, the HDL proteome constitutes anti-inflammatory particles, but in the presence of an acute phase response or systemic inflammation the HDL proteome is remodelled to constitute particles that enhance the inflammatory response (Figure 1). This system likely evolved to provide protection against viral and bacterial infections at a time when humans did not live long enough to suffer from chronic inflammatory diseases such as atherosclerosis or rheumatoid arthritis.4,5 The work of Zewinger et al.1 suggests that therapies that modulate this aspect of the innate immune system may have the potential to improve the outcomes of such chronic inflammatory diseases.Figure 1


Further evidence that high-density lipoprotein is a chameleon-like lipoprotein.

Fogelman AM - Eur. Heart J. (2015)

A schematic representation of the chameleon-like nature of HDL. In the non-inflammatory state, HDL contains little serum amyloid A (SAA) and promotes cholesterol efflux from macrophages, inhibits the production of reactive oxygen species (ROS) and increases nitric oxide (NO) production from endothelial cells. In the presence of an acute phase response or systemic inflammation the positive acute phase reactant SAA is produced by the liver and other tissues and associates with HDL. In the process of SAA associating with HDL, the HDL proteome is remodelled by reducing cardioprotective proteins associated with HDL. As a result, HDL-mediated cholesterol efflux is reduced, ROS production is stimulated and NO production is decreased, which leads to an enhancement of the inflammatory state.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644254&req=5

EHV465F1: A schematic representation of the chameleon-like nature of HDL. In the non-inflammatory state, HDL contains little serum amyloid A (SAA) and promotes cholesterol efflux from macrophages, inhibits the production of reactive oxygen species (ROS) and increases nitric oxide (NO) production from endothelial cells. In the presence of an acute phase response or systemic inflammation the positive acute phase reactant SAA is produced by the liver and other tissues and associates with HDL. In the process of SAA associating with HDL, the HDL proteome is remodelled by reducing cardioprotective proteins associated with HDL. As a result, HDL-mediated cholesterol efflux is reduced, ROS production is stimulated and NO production is decreased, which leads to an enhancement of the inflammatory state.
Mentions: The studies by Zewinger et al.1 as reported in this issue of the Journal provide further evidence of the chameleon-like nature of HDL. In the absence of an acute phase response or systemic inflammation, the HDL proteome constitutes anti-inflammatory particles, but in the presence of an acute phase response or systemic inflammation the HDL proteome is remodelled to constitute particles that enhance the inflammatory response (Figure 1). This system likely evolved to provide protection against viral and bacterial infections at a time when humans did not live long enough to suffer from chronic inflammatory diseases such as atherosclerosis or rheumatoid arthritis.4,5 The work of Zewinger et al.1 suggests that therapies that modulate this aspect of the innate immune system may have the potential to improve the outcomes of such chronic inflammatory diseases.Figure 1

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA afogelman@mednet.ucla.edu.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Zewinger et al. studied 3310 patients undergoing coronary angiography in the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study and determined that serum amyloid A (SAA) concentrations predicted all-cause and cardiovascular mortality... Patients with low SAA levels and higher high-density lipoprotein (HDL) cholesterol levels had lower all-cause and cardiovascular mortality... In contrast, patients with high SAA levels and higher HDL cholesterol levels had increased all-cause and cardiovascular mortality... In the KORA S4 Study, 4261 participants were recruited; subjects with previous myocardial infarction (n = 77), stroke (n = 48) or with missing values for HDL cholesterol or SAA were excluded (n = 102) as well as those lost to follow-up (n = 7)... In these populations, HDL cholesterol levels did not predict outcomes, but higher levels of the calculated biologically ‘effective’ HDL cholesterol were associated with reduced risk for all-cause mortality as well as reduced cardiovascular endpoints... In vitro studies showed that SAA-supplemented HDL reduced endothelial nitric oxide (NO) production and increased endothelial production of reactive oxygen species, leading to the loss of the ability of the HDL to decrease adhesion of mononuclear cells to TNF-α-treated endothelial cells... The authors concluded that ‘SAA turned HDL into a pro-inflammatory particle’... Consistent with this hypothesis, Ansell et al. reported that subjects with high levels of HDL cholesterol with coronary heart disease had pro-inflammatory HDL, while normal subjects had anti-inflammatory HDL... Besler et al. demonstrated that HDL from patients with coronary artery disease lacked endothelial anti-inflammatory effects and did not stimulate endothelial repair because it failed to induce endothelial nitric oxide (eNOS) production... HDL taken from subjects with rheumatoid arthritis had impaired ability to stimulate cholesterol efflux... Charles-Schoenman et al. studied 36 patients with rheumatoid arthritis that were treated with tofacitinib (an oral Janus kinase inhibitor) for 6 weeks and found a trend toward lower SAA levels (51.93 ± 95.61 vs. 24.97 ± 48.96 mg/L; P = 0.0588) and HDL-associated SAA levels (34.76 ± 62.83 vs. 17.79 ± 34.45 mg/L; P = 0.0647), suggesting that resolution of inflammation decreases both plasma levels of SAA and levels of HDL-associated SAA.

Show MeSH
Related in: MedlinePlus