Phospholipid-protein interactions in human low density lipoprotein detected by phosphorus-31 nuclear magnetic resonance

Biochemistry ◽  
1977 ◽  
Vol 16 (15) ◽  
pp. 3487-3491 ◽  
Author(s):  
Philip L. Yeagle ◽  
Robert G. Langdon ◽  
R. Bruce Martin
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Protein Interactions ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Nuclear Magnetic

scholarly journals Establishing reference intervals for triglyceride-containing lipoprotein subfraction metabolites measured using nuclear magnetic resonance spectroscopy in a UK population

2020 ◽  
pp. 000456322096175
Author(s):  
Roshni Joshi ◽  
Goya Wannamethee ◽  
Jorgen Engmann ◽  
Tom Gaunt ◽  
Deborah A Lawlor ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Reference Interval ◽  
Reference Intervals ◽  
Low Density ◽  
Lipoprotein Subfractions ◽  
Nuclear Magnetic

Background Nuclear magnetic resonance (NMR) spectroscopy allows triglycerides to be subclassified into 14 different classes based on particle size and lipid content. We recently showed that these subfractions have differential associations with cardiovascular disease events. Here we report the distributions and define reference interval ranges for 14 triglyceride-containing lipoprotein subfraction metabolites. Methods Lipoprotein subfractions using the Nightingale NMR platform were measured in 9073 participants from four cohort studies contributing to the UCL-Edinburgh-Bristol consortium. The distribution of each metabolite was assessed, and reference interval ranges were calculated for a disease-free population, by sex and age group (<55, 55–65, >65 years), and in a subgroup population of participants with cardiovascular disease or type 2 diabetes. We also determined the distribution across body mass index and smoking status. Results The largest reference interval range was observed in the medium very-low density lipoprotein subclass (2.5th 97.5th percentile; 0.08 to 0.68 mmol/L). The reference intervals were comparable among male and female participants, with the exception of triglyceride in high-density lipoprotein. Triglyceride subfraction concentrations in very-low density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein and high-density lipoprotein subclasses increased with increasing age and increasing body mass index. Triglyceride subfraction concentrations were significantly higher in ever smokers compared to never smokers, among those with clinical chemistry measured total triglyceride greater than 1.7 mmol/L, and in those with cardiovascular disease, and type 2 diabetes as compared to disease-free subjects. Conclusion This is the first study to establish reference interval ranges for 14 triglyceride-containing lipoprotein subfractions in samples from the general population measured using the nuclear magnetic resonance platform. The utility of nuclear magnetic resonance lipid measures may lead to greater insights for the role of triglyceride in cardiovascular disease, emphasizing the importance of appropriate reference interval ranges for future clinical decision making.

scholarly journals Altered Serum Metabolic Profile Assessed by Advanced 1H-NMR in Breast Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4281
Author(s):  
Josep Gumà ◽  
Jose Adriá-Cebrián ◽  
Belen Ruiz-Aguado ◽  
Cinta Albacar ◽  
Josefa Girona ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Cancer Patients ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Breast Cancer Patients ◽  
Altered Lipid ◽  
Nuclear Magnetic

Background: Altered lipid metabolism has been described in some types of cancer. To analyse in depth the metabolic modifications in breast cancer patients, advanced 1H-nuclear magnetic resonance was performed in these patients. The main objective of this paper was to define a specific lipidomic signature for these cancer patients. Materials and methods: Serum from 240 women (171 breast cancer patients and 69 control women) were studied and analysed by nuclear magnetic resonance. Results: Triglyceride-enriched particles, specifically very low-density lipoprotein triglycerides, intermediate-density lipoprotein triglycerides, low-density lipoprotein triglycerides, and high-density lipoprotein triglycerides, were positively associated with breast cancer. Moreover, alanine, tyrosine, and branched amino acids were also associated with increased risk of breast cancer. Conclusions: Breast cancer patients showed a modified metabolome, giving a very interesting tool to draw different radar charts between control women and breast cancer patients. To our knowledge, this is the first time that advanced nuclear magnetic resonance profiling has been used to identify relevant and specifically altered lipid or amino acid metabolites in BC serum samples. The altered metabolic signature could be analysed for early and reliable BC patient diagnosis and prognosis.

scholarly journals PCSK9 Activity Is Potentiated Through HDL Binding

2021 ◽  
Author(s):  
Sean A Burnap ◽  
Katherine Sattler ◽  
Raimund Pechlaner ◽  
Elisa Duregotti ◽  
Ruifang Lu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Size Exclusion ◽  
Low Density ◽  
Postprandial Lipaemia ◽  
Apolipoprotein C3 ◽  
Nuclear Magnetic

Rationale: Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulates in a free and lipoprotein-bound form, yet the functional consequence of the association between PCSK9 and high-density lipoprotein (HDL) remains unexplored. Objective: This study sought to interrogate the novel relationship between PCSK9 and HDL in humans. Methods and Results: Comparing lipoprotein and apolipoprotein profiles by nuclear magnetic resonance and targeted mass spectrometry measurements with PCSK9 levels in the community-based Bruneck (n=656) study revealed a positive association of plasma PCSK9 with small HDL, alongside a highly significant positive correlation between plasma levels of PCSK9 and apolipoprotein-C3, an inhibitor of lipoprotein lipase. The latter association was replicated in an independent cohort, the SAPHIR study (n=270). Thus, PCSK9-HDL association was determined during the postprandial response in two dietary studies (n=20 participants each, 8 times points). Peak triglyceride levels coincided with an attenuation of the PCSK9-HDL association, a loss of apolipoprotein-C3 from HDL and lower levels of small HDL as measured by nuclear magnetic resonance. Crosslinking mass spectrometry (XLMS) upon isolated HDL identified PCSK9 as a potential HDL-binding partner. PCSK9 association with HDL was confirmed through size-exclusion chromatography and immuno-isolation. Quantitative proteomics upon HDL isolated from patients with coronary artery disease (n=172) returned PCSK9 as a core member of the HDL proteome. Combined interrogation of the HDL proteome and lipidome revealed a distinct cluster of PCSK9, phospholipid transfer protein, clusterin and apolipoprotein-E within the HDL proteome, that was altered by sex and positively correlated with sphingomyelin content. Mechanistically, HDL facilitated PCSK9-mediated low-density lipoprotein receptor degradation and reduced low-density lipoprotein uptake through the modulation of PCSK9 internalisation and multimerisation. Conclusions: This study reports HDL as a binder of PCSK9 and regulator of its function. The combination of -omic technologies revealed postprandial lipaemia as a driver of PCSK9 and apolipoprotein-C3 release from HDL.

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