Increased concentration of clusterin/apolipoprotein J (apoJ) in hyperlipemic serum is paradoxically associated with decreased apoJ content in lipoproteins

Rull, Anna; Martínez-Bujidos, M.; Pérez-Cuellar, Montserrat; Pérez, Antonio; Ordóñez-Llanos, Jordi; Sánchez-Quesada, José Luís

doi:10.1016/j.atherosclerosis.2015.06.003

Cited by 16 publications

(11 citation statements)

References 38 publications

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“…Nevertheless, concentrations determined with the novel LC‐MS/MS assay were consistent with previously reported reference ranges for all apos, but apoJ and apoH . However, individual concentrations of both proteins were in accordance with previously published data …”

Section: Discussionsupporting

confidence: 91%

Targeted On‐line SPE‐LC‐MS/MS Assay for the Quantitation of 12 Apolipoproteins from Human Blood

et al. 2018

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Laborious sample pretreatment of biological samples represents the most limiting factor for the translation of targeted proteomics assays from research to clinical routine. An optimized method for the simultaneous quantitation of 12 major apolipoproteins (apos) combining on-line SPE and fast LC-MS/MS analysis in 6.5 min total run time was developed, reducing the manual sample pretreatment time of 3 μL serum or plasma by 60%. Within-run and between-day imprecisions below 10 and 15% (n = 10) and high recovery rates (94-131%) were obtained applying the high-throughput setup. High-quality porcine trypsin was used, which outperformed cost-effective bovine trypsin regarding digestion efficiency. Comparisons with immunoassays and another LC-MS/MS assay demonstrated good correlation (Pearson's R: 0.81-0.98). Further, requirements on sample quality concerning sampling, processing, and long-term storage up to 1 year were investigated revealing significant influences of the applied sampling material and coagulant on quantitation results. Apo profiles of 1339 subjects of the LIFE-Adult-Study were associated with lifestyle and physiological parameters as well as establish parameters of lipid metabolism (e.g., triglycerides, cholesterol). Besides gender effects, most significant impact was seen regarding lipid-lowering medication. In conclusion, this novel highly standardized, high-throughput targeted proteomics assay utilizes a fast, simultaneous analysis of 12 apos from least sample amounts.

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Section: Discussionsupporting

confidence: 91%

Targeted On‐line SPE‐LC‐MS/MS Assay for the Quantitation of 12 Apolipoproteins from Human Blood

et al. 2018

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“…Another important observation is that the plasma concentration of apoJ was increased in both FCH groups. Paradoxically, the proportion of apoJ bound to lipoproteins was lower in the HTG group, due mainly to a low proportion associated with VLDL and LDL, which concurs with a previous study by our group [38]. The content of apoJ in lipoproteins is altered in patients with coronary heart disease or with cardiovascular risk factors [9,39,40].…”

Section: Discussionsupporting

confidence: 91%

Familial Combined Hyperlipidemia (FCH) Patients with High Triglyceride Levels Present with Worse Lipoprotein Function Than FCH Patients with Isolated Hypercholesterolemia

et al. 2020

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Lipoprotein characteristics were analyzed in familial combined hyperlipidemia (FCH) patients before and after statin treatment. Twenty-six FCH patients were classified according to the presence (HTG group, n = 13) or absence (normotriglyceridemic (NTG) group, n = 13) of hypertriglyceridemia. Fifteen healthy subjects comprised the control group. Lipid profile, inflammation markers, and qualitative characteristics of lipoproteins were assessed. Both groups of FCH subjects showed high levels of plasma C-reactive protein (CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and apolipoprotein J. Statins reverted the increased levels of Lp-PLA2 and CRP. Lipoprotein composition alterations detected in FCH subjects were much more frequent in the HTG group, leading to dysfunctional low-density lipoproteins (LDL) and high-density lipoproteins (HDL). In the HTG group, LDL was smaller, more susceptible to oxidation, and contained more electronegative LDL (LDL(-)) compared to the NTG and control groups. Regarding HDL, the HTG group had less Lp-PLA2 activity than the NTG and control groups. HDL from both FCH groups was less anti-inflammatory than HDL from the control group. Statins increased LDL size, decreased LDL(-), and lowered Lp-PLA2 in HDL from HTG. In summary, pro-atherogenic alterations were more frequent and severe in the HTG group. Statins improved some alterations, but many remained unchanged in HTG.

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“…As mentioned initially, sCLU was also described as an apolipoprotein (apoJ) which is present in serum (free and bound to high density lipoprotein (HDL) particles). sCLU(apoJ)-containing HDLs account for approximately 2% of plasma HDLs (125) with about 20% of the circulating sCLU being actually bound to HDLs (126). In contrast to the brain, sCLU(apoJ)-containing HDL particles in plasma are more lipid-rich (38,127).…”

Section: Sclu and The Nervous Systemmentioning

confidence: 99%

The CLU-files: disentanglement of a mystery

Rohne¹,

Prochnow²,

Koch-Brandt³

2016

Biomolecular Concepts

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The multifaceted protein clusterin (CLU) has been challenging researchers for more than 35 years. The characterization of CLU as a molecular chaperone was one of the major breakthroughs in CLU research. Today, secretory clusterin (sCLU), also known as apolipoprotein J (apoJ), is considered one of the most important extracellular chaperones ever found. It is involved in a broad range of physiological and pathophysiological functions, where it exerts a cytoprotective role. Descriptions of various forms of intracellular CLU have led to further and even contradictory functions. To untangle the current state of knowledge of CLU, this review will combine old views in the field, with new discoveries to highlight the nature and function of this fascinating protein(s). In this review, we further describe the expression and subcellular location of various CLU forms. Moreover, we discuss recent insights into the structure of CLU and assess how structural properties as well as the redox environment determine the chaperone activity of CLU. Eventually, the review connects the biochemistry and molecular cell biology of CLU with medical aspects, to formulate a hypothesis of a CLU function in health and disease.

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Increased concentration of clusterin/apolipoprotein J (apoJ) in hyperlipemic serum is paradoxically associated with decreased apoJ content in lipoproteins

Cited by 16 publications

References 38 publications

Targeted On‐line SPE‐LC‐MS/MS Assay for the Quantitation of 12 Apolipoproteins from Human Blood

Targeted On‐line SPE‐LC‐MS/MS Assay for the Quantitation of 12 Apolipoproteins from Human Blood

Familial Combined Hyperlipidemia (FCH) Patients with High Triglyceride Levels Present with Worse Lipoprotein Function Than FCH Patients with Isolated Hypercholesterolemia

The CLU-files: disentanglement of a mystery

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