Shotgun proteomic analysis reveals proteome alterations in HDL of patients with cholesteryl ester transfer protein deficiency

Okada, Takeshi; Ohama, Tohru; Takafuji, Kazuaki; Kanno, Kotaro; Matsuda, Hirohisa; Sairyo, Masami; Zhu, Yinghong; Saga, Ayami; Kobayashi, Takuya; Masuda, Daisuke; Koseki, Masahiro; Nishida, Makoto; Sakata, Yasushi; Yamashita, Shizuya

doi:10.1016/j.jacl.2019.01.002

Cited by 23 publications

(23 citation statements)

References 45 publications

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“…The mechanisms that underlie our observations are not yet known. A possible explanation is that the presence of C3 on the surface of lipoproteins [6][7][8] may affect their metabolism. This idea is supported by the observation that complement C1r, a component of the classical complement pathway, was indeed in vitro shown to bind phospholipid transfer protein and to partially stabilize its lipid transfer function.…”

Section: Discussionmentioning

confidence: 99%

“…C4 and C9 are present on very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). [6][7][8] This suggests a possible relationship between the complement system and metabolism and/or function of circulating lipoproteins. Experimental findings also suggest that the complement system, particularly the alternative pathway, may be causally involved in lipid metabolism.…”

Section: Introductionmentioning

confidence: 99%

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C3 and alternative pathway components are associated with an adverse lipoprotein subclass profile: The CODAM study

Xin

Hertle

Kallen

et al. 2021

Journal of Clinical Lipidology

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BACKGROUND: Plasma lipoproteins contain heterogeneous subclasses. Previous studies on the associations of the complement system with lipids and lipoproteins are mainly limited to the major lipid classes, and associations of complement with lipoprotein subclass characteristics remain unknown. OBJECTIVE: We investigated the associations of C3 and other components of the alternative complement pathway with plasma lipoprotein subclass profile. METHODS: Plasma complement concentrations (complement component 3 [C3], properdin, factor H, factor D, MASP-3, C3a, Bb), and lipoprotein subclass profile (as measured by nuclear magnetic resonance spectroscopy) were obtained in 523 participants (59.6 6 6.9 years, 60.8% men) of the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study. Multiple linear regression was used to investigate the associations of C3 (primary determinant) and other alternative pathway components (secondary determinants) with characteristics (particle concentration and size [main outcomes], and lipid contents [secondary outcomes]) of 14 lipoprotein subclasses, ranging from extremely large VLDL to small HDL (all standardized [std] values). RESULTS: Participants with higher C3 concentrations had more circulating VLDL (stdbs ranging from 0.27 to 0.36), IDL and LDL (stdbs ranging from 0.14 to 0.17), and small HDL (stdb 5 0.21). In contrast, they had fewer very large and large HDL particles (stdbs 5 20.36). In persons with higher C3 concentrations, all lipoprotein subclasses were enriched in triglycerides. Similar but weaker associations were observed for properdin, factor H, factor D, and MASP-3, but not for C3a and Bb.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

C3 and alternative pathway components are associated with an adverse lipoprotein subclass profile: The CODAM study

Xin

Hertle

Kallen

et al. 2021

Journal of Clinical Lipidology

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“…ApoA-II is only synthesized in the liver, represents approximately 20% of HDL protein, and is present on about two-thirds of HDL particles in humans [13,14]. Besides apoA -I and -II, HDLs express other apolipoproteins, which, in order of detection, include ApoC-III, ApoL1, ApoA-II, ApoE, ApoC-I, ApoC-II, and ApoM [15]. At a lipid level, more than 200 lipid species have been identified to constitute HDL particles [16].…”

Section: Molecules Carried By Hdl Particlesmentioning

confidence: 99%

Advances in HDL: Much More than Lipid Transporters

Ben‐Aicha

Badimon

Vilahur

2020

IJMS

103

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High Density Lipoprotein (HDL) particles, beyond serving as lipid transporters and playing a key role in reverse cholesterol transport, carry a highly variable number of proteins, micro-RNAs, vitamins, and hormones, which endow them with the ability to mediate a plethora of cellular and molecular mechanisms that promote cardiovascular health. It is becoming increasingly evident, however, that the presence of cardiovascular risk factors and co-morbidities alters HDLs cargo and protective functions. This concept has led to the notion that metrics other than HDL-cholesterol levels, such as HDL functionality and composition, may better capture HDL cardiovascular protection. On the other hand, the potential of HDL as natural delivery carriers has also fostered the design of engineered HDL-mimetics aiming to improve HDL efficacy or as drug-delivery agents with therapeutic potential. In this paper, we first provide an overview of the molecules known to be transported by HDL particles and mainly discuss their functions in the cardiovascular system. Second, we describe the impact of cardiovascular risk factors and co-morbidities on HDL remodeling. Finally, we review the currently developed HDL-based approaches.

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“…The increment in the HDL levels by CETP inhibitors is another biomarker that has continued to be disappointing in clinical research. In fact, in patients with deficiency of CETP (CETP-D), the HDL particles are enriched with ApoE, angiopoietin-like3 protein, and complement regulatory proteins such as C3, C4a, C4b, and C9 that could be associated to the increased atherogenic profile in CETP-D patients [91].…”

Section: Hdl Lipoproteomics For Drug Discoverymentioning

confidence: 99%

Lipoproteomics: Methodologies and Analysis of Lipoprotein-Associated Proteins along with the Drug Intervention

Torres‐Romero¹,

Lara-Riegos²,

Parra³

et al. 2021

Drug Design - Novel Advances in the Omics Field and Applications

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Lipoproteins are specialized particles involved in the transport and distribution of hydrophobic lipids, as cholesterol and triglycerides, throughout the body. The lipoproteins exhibit a basic spherical shape as complexes of lipids and proteins, and these latter are known as apolipoproteins. Initially, the proteins associated with lipoproteins were recognized as integral or peripheral proteins that only maintain the dynamics and metabolism of lipoproteins. However, there exist many studies on different lipoproteins evidencing that the quantity and type of apolipoproteins and lipoprotein-associated proteins are diverse and could be associated with different lipoprotein function outcomes. Here, we summarized recent processes in the determination of apolipoproteins and lipoprotein-associated proteins profiles through a proteomic approach, analyzing the major methods available and are used to achieve this. We also discuss the relevance of these lipoproteomic analyses on the human disease outcomes.

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Shotgun proteomic analysis reveals proteome alterations in HDL of patients with cholesteryl ester transfer protein deficiency

Cited by 23 publications

References 45 publications

C3 and alternative pathway components are associated with an adverse lipoprotein subclass profile: The CODAM study

C3 and alternative pathway components are associated with an adverse lipoprotein subclass profile: The CODAM study

Advances in HDL: Much More than Lipid Transporters

Lipoproteomics: Methodologies and Analysis of Lipoprotein-Associated Proteins along with the Drug Intervention

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