Structure-function relationships of HDL in diabetes and coronary heart disease

Cardner, Mathias; Yalçinkaya, Mustafa; Goetze, Sandra; Luca, Edlira; Baláž, Miroslav; Hunjadi, Monika; Hartung, Johannes; Shemet, Andrej; Kränkel, Nicolle; Radosavljevic, Silvija; Keel, Michaela; Othman, Alaa; Karsai, Gergely; Hornemann, Thorsten; Claassen, Manfred; Liebisch, Gerhard; Carreira, Erick M.; Ritsch, Andreas; Landmesser, Ulf; Krützfeldt, Jan; Wolfrum, Christian; Wollscheid, Bernd; Beerenwinkel, Niko; Rohrer, Lucia; Eckardstein, Arnold von

doi:10.1172/jci.insight.131491

Cited by 78 publications

(118 citation statements)

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“…In total, we identified eight studies using NMR or LC-MS for lipidomic analyses, all based on a relatively small sample size (number of participants ranging from 20 to 159). Most of the studies were conducted in hospital settings using cross-sectional or case-control designs [59][60][61][62][63][64][65]. Three studies conducted lipidomics of HDL and non-HDL particles [51,52,64], while five studies specifically focused on the lipidome of HDLs [61][62][63]65,66].…”

Section: Summary Of Recent Studies On Lipidomics Of Lipoproteins Andmentioning

confidence: 99%

“…Most of the studies were conducted in hospital settings using cross-sectional or case-control designs [59][60][61][62][63][64][65]. Three studies conducted lipidomics of HDL and non-HDL particles [51,52,64], while five studies specifically focused on the lipidome of HDLs [61][62][63]65,66]. Of the five studies, two studies examined varieties in HDL lipid content, comparing participants with high HDL-c to those with low HDL-c [61,66], and the other studies focused on the lipidome of lipoproteins and CHD diagnosis and progression [51,52,[62][63][64][65].…”

Section: Summary Of Recent Studies On Lipidomics Of Lipoproteins Andmentioning

confidence: 99%

“…Three studies conducted lipidomics of HDL and non-HDL particles [51,52,64], while five studies specifically focused on the lipidome of HDLs [61][62][63]65,66]. Of the five studies, two studies examined varieties in HDL lipid content, comparing participants with high HDL-c to those with low HDL-c [61,66], and the other studies focused on the lipidome of lipoproteins and CHD diagnosis and progression [51,52,[62][63][64][65]. Only one study included LDL-c as a covariate [62], and only three studies corrected for multiple testing [63][64][65].…”

Section: Summary Of Recent Studies On Lipidomics Of Lipoproteins Andmentioning

confidence: 99%

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A Review of Lipidomics of Cardiovascular Disease Highlights the Importance of Isolating Lipoproteins

Ding

Rexrode

2020

Metabolites

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Cutting-edge lipidomic profiling measures hundreds or even thousands of lipids in plasma and is increasingly used to investigate mechanisms of cardiovascular disease (CVD). In this review, we introduce lipidomic techniques, describe distributions of lipids across lipoproteins, and summarize findings on the association of lipids with CVD based on lipidomics. The main findings of 16 cohort studies were that, independent of total and high-density lipoprotein cholesterol (HDL-c), ceramides (d18:1/16:0, d18:1/18:0, and d18:1/24:1) and phosphatidylcholines (PCs) containing saturated and monounsaturated fatty acyl chains are positively associated with risks of CVD outcomes, while PCs containing polyunsaturated fatty acyl chains (PUFA) are inversely associated with risks of CVD outcomes. Lysophosphatidylcholines (LPCs) may be positively associated with risks of CVD outcomes. Interestingly, the distributions of the identified lipids vary across lipoproteins: LPCs are primarily contained in HDLs, ceramides are mainly contained in low-density lipoproteins (LDLs), and PCs are distributed in both HDLs and LDLs. Thus, the potential mechanism behind previous findings may be related to the effect of the identified lipids on the biological functions of HDLs and LDLs. Only eight studies on the lipidomics of HDL and non-HDL particles and CVD outcomes have been conducted, which showed that higher triglycerides (TAGs), lower PUFA, lower phospholipids, and lower sphingomyelin content in HDLs might be associated with a higher risk of coronary heart disease (CHD). However, the generalizability of these studies is a major concern, given that they used case-control or cross-sectional designs in hospital settings, included a very small number of participants, and did not correct for multiple testing or adjust for blood lipids such as HDL-c, low-density lipoprotein cholesterol (LDL-c), or TAGs. Overall, findings from the literature highlight the importance of research on lipidomics of lipoproteins to enhance our understanding of the mechanism of the association between the identified lipids and the risk of CVD and allow the identification of novel lipid biomarkers in HDLs and LDLs, independent of HDL-c and LDL-c. Lipidomic techniques show the feasibility of this exciting research direction, and the lack of high-quality epidemiological studies warrants well-designed prospective cohort studies.

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Section: Summary Of Recent Studies On Lipidomics Of Lipoproteins Andmentioning

confidence: 99%

Section: Summary Of Recent Studies On Lipidomics Of Lipoproteins Andmentioning

confidence: 99%

Section: Summary Of Recent Studies On Lipidomics Of Lipoproteins Andmentioning

confidence: 99%

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A Review of Lipidomics of Cardiovascular Disease Highlights the Importance of Isolating Lipoproteins

Ding

Rexrode

2020

Metabolites

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“…PHLD hydrolyzes the glycan-phosphatidylinositol linkages of glycosylphosphatidylinositol-anchored cell surface proteins. We previously showed that PHLD inhibits apoptosis in human aortic endothelial cells, and thereby exerts a presumably vasoprotective function (3). Also, we identified several relatively low-abundant Ras-related proteins that are enriched in HDL particles from patients including RAB6A, RB11A/B, RAB1B, and RP1BL (Fig.…”

Section: Discussionmentioning

confidence: 66%

“…Low plasma levels of HDL cholesterol (HDL-C) are associated with higher risk of several diseases including coronary heart disease (CHD) and diabetes mellitus type 2 (T2DM) (3). However, the cholesterol content of HDL particles does not seem to be causative of disease development.…”

Section: Introductionmentioning

confidence: 99%

Sensitive and reproducible determination of clinical HDL proteotypes

Goetze

Frey²,

Rohrer³

et al. 2020

Preprint

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AbstractBackgroundHigh-density lipoprotein (HDL) is a heterogenous mixture of blood-circulating multimolecular particles containing many different proteins, lipids, and RNAs. Recent advancements in mass spectrometry-based proteotype analysis strategies enable the sensitive and reproducible quantification of proteins across large patient cohorts.MethodsHDL particles were isolated from plasma of more than 300 healthy individuals or patients with a multiplicity of physiological HDL states. From these, peptides were extracted and HDL proteome spectral libraries were generated. This is a prerequisite for using data-independent acquisition (DIA) strategies to analyze HDL particles from clinical cohorts using mass spectrometry.ResultsThe resulting HDL proteome spectral libraries consist of 296 protein groups and 341 peptidoforms of potential biological significance identified with high confidence. We used the HDL proteome libraries to evaluate HDL proteotype differences in between healthy individuals and patients suffering from diabetes mellitus type 2 (T2DM) and/or coronary heart disease (CHD). Bioinformatic interrogation of the data revealed significant quantitative differences in the HDL proteotypes including a significant depletion of phosphatidylinositol-glycan-specific phospholipase D (PHLD) from disease-derived HDL particles.ConclusionThe DIA-based HDL proteotyping strategy enabled sensitive and reproducible digitization of HDL proteotypes derived from patient cohorts and provides new insights into the composition of HDL particles as a rational basis to decode structure-function-disease relationships of HDL.List of human genes and protein names discussed in the paper- APOA1 (Apolipoprotein A-I)- APOA2 (Apolipoprotein A-II)- APOE (Apolipoprotein E)- APOC3 (Apolipoprotein C3)- CLUS (Clusterin)- PHLD (Phosphatidylinositol-glycan-specific phospholipase D)- PON1 (Serum paraoxonase/arylesterase 1)- PON3 (Serum paraoxonase/lactonase 3)- PSPB (Pulmonary surfactant-associated protein B)- RAB1B (Ras-related protein Rab-1B)- RAB6A (Ras-related protein Rab-6A)- RB11A/B (Ras-related protein Rab-11A/B)- RP1BL (Ras-related protein Rap-1b-like protein)- RAB10 (Ras-related protein Rab-10)- SAA1 (Serum amyloid A-1 protein)- SAA2 (Serum amyloid A-2 protein)- SAA4 (Serum amyloid A-4 protein)- SCRB1 (Scavenger receptor class B member 1)

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Lipidomics in Biomarker Research

Hornemann

2021

Prevention and Treatment of Atherosclerosis

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Lipids are natural substances found in all living organisms and involved in many biological functions. Imbalances in the lipid metabolism are linked to various diseases such as obesity, diabetes, or cardiovascular disease. Lipids comprise thousands of chemically distinct species making them a challenge to analyze because of their great structural diversity.Thanks to the technological improvements in the fields of chromatography, high-resolution mass spectrometry, and bioinformatics over the last years, it is now possible to perform global lipidomics analyses, allowing the concomitant detection, identification, and relative quantification of hundreds of lipid species. This review shall provide an insight into a general lipidomics workflow and its application in metabolic biomarker research.

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Structure-function relationships of HDL in diabetes and coronary heart disease

Cited by 78 publications

References 78 publications

A Review of Lipidomics of Cardiovascular Disease Highlights the Importance of Isolating Lipoproteins

A Review of Lipidomics of Cardiovascular Disease Highlights the Importance of Isolating Lipoproteins

Sensitive and reproducible determination of clinical HDL proteotypes

Lipidomics in Biomarker Research

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