HDL Isolated by Immunoaffinity, Ultracentrifugation, or Precipitation is Compositionally and Functionally Distinct

Holzer, Michael; Ljubojević-Holzer, Senka; Souza, Douglas Ricardo de; Stadler, Julia T.; Rani, Alankrita; Scharnagl, Hubert; Ronsein, Graziella Eliza; Marsche, Gunther

doi:10.1016/j.jlr.2022.100307

Cited by 12 publications

(9 citation statements)

References 45 publications

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“…We also found some traces of APOB and LPA despite using the two-step sequential ultracentrifugation method, which first separates APOB-containing lipoprotein particles followed by separation of the APOA1-containing particles. APOB, referring to APOB-100 protein, is integral part of Lp(a)-particles with density similar to HDL, thus it is not uncommon to identify these traces HDL proteomics as also reported by Holtzer et al 61 . In their comparative study of three different HDL particle isolation methods, they found all methods to result in the same contaminants or co-eluents.…”

Section: Figure 8 Discussionmentioning

confidence: 65%

“…This may, alas, also hide some individual findings and mask outliers by causing regression to mean. Thirdly, HDL particles can be isolated with many different methods each providing compositionally and functionally slightly different HDL particle pools 61 . Here, we chose the most common method that has been available since the 50's, the density gradient ultracentrifugation.…”

Section: Figure 8 Discussionmentioning

confidence: 99%

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Proteomics and lipidomics of high-density lipoprotein: Perimenopause is characterized by small triacylglycerols-enriched particles

Lehti,

Korhonen,

Soliymani

et al. 2024

Preprint

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Menopause is associated with a proatherogenic shift in serum metabolome and high-density lipoprotein (HDL) particle size distribution. We analyzed lipidomes and proteomes of HDL with nuclear magnetic resonance and mass spectrometry from pre-, peri-, and postmenopausal women to get a deeper insight into the structure of HDL. The S-HDL particles constituted 62% of all HDL particles in perimenopause and 60% in pre- and postmenopause, thus, perimenopausal HDL had the highest S-HDL lipid content, notably, being enriched in triacylglycerols. This feature is a known risk factor for coronary heart disease. We identified 728 proteins from the purified HDL particles and quantified 44 representing functional classes of lipid metabolism, transport and signaling, immune defense, and regulation of cellular processes. Perimenopausal HDL exhibited fewer apolipoproteins (APOA1, APOA2, APOC1, APOC3, and APOE) per particle than premenopausal. We did not detect menopausal status-associated deteriorations in the LCAT activity or cholesterol efflux capacity, albeit the calculated lipid class ratios suggest defects, especially within PERI XL-HDL particles, potentially affecting the particle size distribution and triacylglycerol content. In summary, menopause is associated with structural differences in HDL potentially compromising the cardioprotective quality of HDL.

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Section: Figure 8 Discussionmentioning

confidence: 65%

Section: Figure 8 Discussionmentioning

confidence: 99%

Proteomics and lipidomics of high-density lipoprotein: Perimenopause is characterized by small triacylglycerols-enriched particles

Lehti,

Korhonen,

Soliymani

et al. 2024

Preprint

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“…The protein cargo of HDLs is comprised of over 100 proteins [ 66 ]. It should be noted that the HDL isolation method has a significant impact on HDL protein composition [ 67 ], which could contribute to some heterogeneity among studies.…”

Section: Hdl Size and Compositionmentioning

confidence: 99%

“…As an illustration, whole serum CEC using human THP-1 macrophages was a strong predictor of survival in a large cohort of patients with acute myocardial infarction, but this association was lost in the same cohort using the combination of apoB-depleted serum with THP-1 cells or the combination of whole serum with ABCA1-overexpressing CHO cells or Fu5AH cells [ 109 ]. In addition, a recent paper found that the HDL isolation procedure clearly modulates CEC results [ 67 ].…”

Section: Hdl Functionsmentioning

confidence: 99%

High-Density Lipoprotein Alterations in Type 2 Diabetes and Obesity

et al. 2023

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Alterations affecting high-density lipoproteins (HDLs) are one of the various abnormalities observed in dyslipidemia in type 2 diabetes mellitus (T2DM) and obesity. Kinetic studies have demonstrated that the catabolism of HDL particles is accelerated. Both the size and the lipidome and proteome of HDL particles are significantly modified, which likely contributes to some of the functional defects of HDLs. Studies on cholesterol efflux capacity have yielded heterogeneous results, ranging from a defect to an improvement. Several studies indicate that HDLs are less able to inhibit the nuclear factor kappa-B (NF-κB) proinflammatory pathway, and subsequently, the adhesion of monocytes on endothelium and their recruitment into the subendothelial space. In addition, the antioxidative function of HDL particles is diminished, thus facilitating the deleterious effects of oxidized low-density lipoproteins on vasculature. Lastly, the HDL-induced activation of endothelial nitric oxide synthase is less effective in T2DM and metabolic syndrome, contributing to several HDL functional defects, such as an impaired capacity to promote vasodilatation and endothelium repair, and difficulty counteracting the production of reactive oxygen species and inflammation.

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“…Lipid poor forms of HDL are small and discoidal, whereas a fully mature HDL particle is spherical, larger and carries additional hydrophobic cargo. The method used for HDL isolation substantially impacts the functional readouts, as each method has its advantage and specific enrichment of some proteins when compared to the others [ 67 ]. Primarily involved in the reverse cholesterol transport from peripheral tissues to the liver, HDL particles have additional anti-oxidant, anti-inflammatory, anti-thrombotic, and anti-apoptotic properties.…”

Section: High-density Lipoproteins Are Self-assembling Nanoparticlesmentioning

confidence: 99%

A Current Update on the Role of HDL-Based Nanomedicine in Targeting Macrophages in Cardiovascular Disease

Rani

Marsche

2023

Pharmaceutics

Self Cite

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High-density lipoproteins (HDL) are complex endogenous nanoparticles involved in important functions such as reverse cholesterol transport and immunomodulatory activities, ensuring metabolic homeostasis and vascular health. The ability of HDL to interact with a plethora of immune cells and structural cells places it in the center of numerous disease pathophysiologies. However, inflammatory dysregulation can lead to pathogenic remodeling and post-translational modification of HDL, rendering HDL dysfunctional or even pro-inflammatory. Monocytes and macrophages play a critical role in mediating vascular inflammation, such as in coronary artery disease (CAD). The fact that HDL nanoparticles have potent anti-inflammatory effects on mononuclear phagocytes has opened new avenues for the development of nanotherapeutics to restore vascular integrity. HDL infusion therapies are being developed to improve the physiological functions of HDL and to quantitatively restore or increase the native HDL pool. The components and design of HDL-based nanoparticles have evolved significantly since their initial introduction with highly anticipated results in an ongoing phase III clinical trial in subjects with acute coronary syndrome. The understanding of mechanisms involved in HDL-based synthetic nanotherapeutics is critical to their design, therapeutic potential and effectiveness. In this review, we provide a current update on HDL-ApoA-I mimetic nanotherapeutics, highlighting the scope of treating vascular diseases by targeting monocytes and macrophages.

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HDL Isolated by Immunoaffinity, Ultracentrifugation, or Precipitation is Compositionally and Functionally Distinct

Cited by 12 publications

References 45 publications

Proteomics and lipidomics of high-density lipoprotein: Perimenopause is characterized by small triacylglycerols-enriched particles

Proteomics and lipidomics of high-density lipoprotein: Perimenopause is characterized by small triacylglycerols-enriched particles

High-Density Lipoprotein Alterations in Type 2 Diabetes and Obesity

A Current Update on the Role of HDL-Based Nanomedicine in Targeting Macrophages in Cardiovascular Disease

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