Lipoprotein profiles in human heterozygote carriers of a functional mutation P297S in scavenger receptor class B1

Ljunggren, Stefan; Levels, Johannes H.M.; Hovingh, Kees; Holleboom, Adriaan G.; Vergeer, Menno; Argyri, Letta; Gkolfinopoulou, Christina; Chroni, Angeliki; Sierts, Jeroen A.; Kastelein, John J.P.; Kuivenhoven, Jan Albert; Lindahl, Mattias; Karlsson, Helén

doi:10.1016/j.bbalip.2015.09.006

Cited by 15 publications

(17 citation statements)

References 46 publications

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“…A naturally occurring missense mutation in SR-B1, P297S has been identified in humans that display elevated HDL-C, decreased cholesterol efflux from monocyte/macrophages, platelet dysfunction, and adrenal steroid hormone (cortisol) deficiency. Taken together, these data support a role for selective HDL–CE uptake in these human tissues (75, 76).…”

Section: Regulation Of Sr-b1 Expressionsupporting

confidence: 68%

SR-B1: A Unique Multifunctional Receptor for Cholesterol Influx and Efflux

Shen

Azhar²,

Kraemer³

2018

Annu. Rev. Physiol.

285

253

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The scavenger receptor, class B type 1 (SR-B1), is a multiligand membrane receptor protein that functions as a physiologically relevant high-density lipoprotein (HDL) receptor whose primary role is to mediate selective uptake or influx of HDL-derived cholesteryl esters into cells and tissues. SR-B1 also facilitates the efflux of cholesterol from peripheral tissues, including macrophages, back to liver. As a regulator of plasma membrane cholesterol content, SR-B1 promotes the uptake of lipid soluble vitamins as well as viral entry into host cells. These collective functions of SR-B1 ultimately affect programmed cell death, female fertility, platelet function, vasculature inflammation, and diet-induced atherosclerosis and myocardial infarction. SR-B1 has also been identified as a potential marker for cancer diagnosis and prognosis. Finally, the SR-B1-linked selective HDL-cholesteryl ester uptake pathway is now being evaluated as a gateway for the delivery of therapeutic and diagnostic agents. In this review, we focus on the regulation and functional significance of SR-B1 in mediating cholesterol movement into and out of cells.

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Section: Regulation Of Sr-b1 Expressionsupporting

confidence: 68%

SR-B1: A Unique Multifunctional Receptor for Cholesterol Influx and Efflux

Shen

Azhar²,

Kraemer³

2018

Annu. Rev. Physiol.

285

253

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“…The effect of P. gingivalis on methionine oxidation was analysed by calculating the ratio of the peptide intensity of the oxidized and nonoxidized methionines at positions 136 ( m / z 1047 and 1031) and 172 ( m / z 1299 and 1283) in the mass spectrum data of apolipoprotein A‐1 (apoA‐1) of HDL (the positions prone to oxidation have been described previously in ref. ).…”

Section: Methodsmentioning

confidence: 97%

“…Twenty microlitres of the diluted plasma was then mixed with 200 μL of phenyl acetate solution, containing 3.26 mmol/L of phenyl acetate in salt buffer. The phenol produced was measured at 270 nm, with 250 nm as background, using a spectrophotometer (SpectraMax 190 plate reader; Molecular Devices, Sunnyvale, CA, USA) and the activity was calculated using the extinction coefficient of phenol of 1310 M/cm and expressed in μmol/min/mL (U/mL) …”

Section: Methodsmentioning

confidence: 99%

Lipoprotein modifications by gingipains of Porphyromonas gingivalis

Lönn

Ljunggren

Klarström-Engström

et al. 2018

J of Periodontal Research

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Background and ObjectiveSeveral studies have shown an association between periodontitis and cardiovascular disease (CVD). Atherosclerosis is the major cause of CVD, and a key event in the development of atherosclerosis is accumulation of lipoproteins within the arterial wall. Bacteria are the primary etiologic agents in periodontitis and Porphyromonas gingivalis is the major pathogen in the disease. Several studies support a role of modified low‐density lipoprotein (LDL) in atherogenesis; however, the pathogenic stimuli that induce the changes and the mechanisms by which this occur are unknown. This study aims to identify alterations in plasma lipoproteins induced by the periodontopathic species of bacterium, P. gingivalis, in vitro.Material and MethodsPlasma lipoproteins were isolated from whole blood treated with wild‐type and gingipain‐mutant (lacking either the Rgp‐ or Kgp gingipains) P. gingivalis by density/gradient‐ultracentrifugation and were studied using 2‐dimensional gel electrophoresis followed by matrix‐assisted laser desorption/ionization mass spectrometry. Porphyromonas gingivalis‐induced lipid peroxidation and antioxidant levels were measured by thiobarbituric acid‐reactive substances and antioxidant assay kits, respectively, and lumiaggregometry was used for measurement of reactive oxygen species (ROS) and aggregation.Results Porphyromonas gingivalis exerted substantial proteolytic effects on the lipoproteins. The Rgp gingipains were responsible for producing 2 apoE fragments, as well as 2 apoB‐100 fragments, in LDL, and the Kgp gingipain produced an unidentified fragment in high‐density lipoproteins. Porphyromonas gingivalis and its different gingipain variants induced ROS and consumed antioxidants. Both the Rgp and Kgp gingipains were involved in inducing lipid peroxidation.Conclusion Porphyromonas gingivalis has the potential to change the expression of lipoproteins in blood, which may represent a crucial link between periodontitis and CVD.

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“…40 Recently, clinical studies have reported a significant increase in Met oxidation of apoAI in patients with CAD and human heterozygote carriers of SR-BI mutation. 38,41 However, the absence of highly specific antibody has impeded the direct detection of MetSO sites in apoAI in this study. Notably, our study showed that hepatic MsrA In addition, plasma LCAT activated by apoAI is responsible for HDL maturation through catalyzing FC esterification.…”

Section: Discussionmentioning

confidence: 97%

Methionine sulfoxide reductase A attenuates atherosclerosis via repairing dysfunctional HDL in scavenger receptor class B type I deficient mice

Zhao

et al. 2020

FASEB j.

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High‐density lipoprotein (HDL), a well‐known atheroprotective factor, can be converted to proatherogenic particles in chronic inflammation. HDL‐targeted therapeutic strategy for atherosclerotic cardiovascular disease (CVD) is currently under development. This study aims to assess the role of methionine sulfoxide reductase A (MsrA) in abnormal HDL and its related disorders in scavenger receptor class B type I deficient (SR‐BI−/−) mice. First, we demonstrated that MsrA overexpression attenuated ROS level and inflammation in HepG2 cells. For the in vivo study, SR‐BI−/− mice were intravenously injected with lentivirus to achieve hepatic MsrA overexpression. High‐level hepatic MsrA significantly reduced the plasma free cholesterol contents, improved HDL functional proteins apolipoprotein A‐I (apoAI), apoE, paraoxonase1 (PON1), and lecithin:cholesterol acyltransferase (LCAT), while decreased the pro‐inflammatory property of dysfunctional HDL, contributing to reduced atherosclerosis and hepatic steatosis in Western diet‐fed mice. Furthermore, the study revealed that hepatic MsrA altered the expression of several genes controlling HDL biogenesis, cholesterol esterification, cholesterol uptake mediated by low‐density lipoprotein receptor (LDLR) and biliary excretion, as well as suppressed nuclear factor κB (NF‐κB) signaling pathway, which largely relied on liver X receptor alpha (LXRα)‐upregulation. These results provide original evidence that MsrA may be a promising target for the therapy of dysfunctional HDL‐related CVD.

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Lipoprotein profiles in human heterozygote carriers of a functional mutation P297S in scavenger receptor class B1

Cited by 15 publications

References 46 publications

SR-B1: A Unique Multifunctional Receptor for Cholesterol Influx and Efflux

SR-B1: A Unique Multifunctional Receptor for Cholesterol Influx and Efflux

Lipoprotein modifications by gingipains of Porphyromonas gingivalis

Methionine sulfoxide reductase A attenuates atherosclerosis via repairing dysfunctional HDL in scavenger receptor class B type I deficient mice

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