Pcpe2, a Novel Extracellular Matrix Protein, Regulates Adipocyte SR-BI–Mediated High-Density Lipoprotein Uptake-Reference-Cited by-同舟云学术

Pcpe2, a Novel Extracellular Matrix Protein, Regulates Adipocyte SR-BI–Mediated High-Density Lipoprotein Uptake

Published:2021-11 Issue:11 Volume:41 Page:2708-2725
ISSN:1079-5642
Container-title:Arteriosclerosis, Thrombosis, and Vascular Biology
language:en
Short-container-title:ATVB

Author:

Xu Hao¹,Thomas Michael J.²³,Kaul Sushma¹,Kallinger Rachel²,Ouweneel Amber B.¹^ORCID,Maruko Elisa¹,Oussaada Sabrina M.⁴,Jongejan Aldo⁵^ORCID,Cense Huib A.⁶,Nieuwdorp Max⁷,Serlie Mireille J.⁴,Goldberg Ira J.⁸^ORCID,Civelek Mete⁹^ORCID,Parks Brian W.¹⁰,Lusis Aldons J.¹¹^ORCID,Knaack Darcy¹²,Schill Rebecca L.¹²¹³^ORCID,May Sarah C.¹²,Reho John J.¹⁴¹⁵,Grobe Justin L.³¹⁴¹⁵¹⁶^ORCID,Gantner Benjamin¹,Sahoo Daisy¹²³¹²,Sorci-Thomas Mary G.¹²³^ORCID

Affiliation:

1. Department of Medicine, Division of Endocrinology and Molecular Medicine (H.X., S.K., A.B.O., E.M., B.G., D.S., M.G.S.-T.), Medical College of Wisconsin, Milwaukee.

2. Pharmacology & Toxicology (M.J.T., R.K., D.S., M.G.S.-T.), Medical College of Wisconsin, Milwaukee.

3. Cardiovascular Center (M.J.T., J.L.G., D.S., M.G.S.-T.), Medical College of Wisconsin, Milwaukee.

4. Department of Endocrinology and Metabolism (S.M.O., M.J.S.), Amsterdam University Medical Centers, Academic Medical Center, the Netherlands.

5. Department of Bioinformatics (A.J.), Amsterdam University Medical Centers, Academic Medical Center, the Netherlands.

6. Department of Surgery, Rode Kruis Ziekenhuis, Beverwijk, the Netherlands (H.A.C.).

7. Department of Internal and Vascular Medicine (M.N.), Amsterdam University Medical Centers, Academic Medical Center, the Netherlands.

8. Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, New York University Langone School of Medicine (I.J.G.).

9. Department of Biomedical Engineering, University of Virginia, Charlottesville (M.C.).

10. Department of Nutritional Sciences, University of Wisconsin-Madison (B.W.P).

11. Department of Medicine, Human Genetics, Microbiology, Immunology and Molecular Genetics, University of California Los Angeles (A.J.L.).

12. Department of Biochemistry (D.K., R.L.S., S.C.M., D.S.), Medical College of Wisconsin, Milwaukee.

13. Now with Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI (R.L.S.).

14. Department of Physiology (J.J.R., J.L.G.), Medical College of Wisconsin, Milwaukee.

15. Comprehensive Rodent Metabolic Phenotyping Core, Department of Physiology, Medical College of Wisconsin, Milwaukee (J.J.R., J.L.G.).

16. Department of Biomedical Engineering (J.L.G.).

Abstract

Objective: To investigate the role of adipocyte Pcpe2 (procollagen C-endopeptidase enhancer 2) in SR-BI (scavenger receptor class BI)–mediated HDL-C (high-density lipoprotein cholesterol) uptake and contributions to adipose lipid storage. Approach and Results: Pcpe2, a glycoprotein devoid of intrinsic proteolytic activity, is believed to participate in extracellular protein-protein interactions, supporting SR-BI– mediated HDL-C uptake. In published studies, Pcpe2 deficiency increased the development of atherosclerosis by reducing SR-BI–mediated HDL-C catabolism, but the biological impact of this deficiency on adipocyte SR-BI–mediated HDL-C uptake is unknown. Differentiated cells from Ldlr −/− / Pcpe2 −/− (Pcpe2 −/− ) mouse adipose tissue showed elevated SR-BI protein levels, but significantly reduced HDL-C uptake compared to Ldlr −/− (control) adipose tissue. SR-BI–mediated HDL-C uptake was restored by preincubation of cells with exogenous Pcpe2. In diet-fed mice lacking Pcpe2, significant reductions in visceral, subcutaneous, and brown adipose tissue mass were observed, despite elevations in plasma triglyceride and cholesterol concentrations. Significant positive correlations exist between adipose mass and Pcpe2 expression in both mice and humans. Conclusions: Overall, these findings reveal a novel and unexpected function for Pcpe2 in modulating SR-BI expression and function as it relates to adipose tissue expansion and cholesterol balance in both mice and humans. Graphic Abstract: A graphic abstract is available for this article.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

Link

https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.121.316615

Reference83 articles.

1. Procollagen C-endopeptidase Enhancer Protein 2 (PCPE2) Reduces Atherosclerosis in Mice by Enhancing Scavenger Receptor Class B1 (SR-BI)-mediated High-density Lipoprotein (HDL)-Cholesteryl Ester Uptake

2. What does procollagen C-endopeptidase enhancer protein 2 have to do with HDL-cholesteryl ester uptake? Or how I learned to stop worrying and love reverse cholesterol transport?

3. Regulation of apoAI processing by procollagen C-proteinase enhancer-2 and bone morphogenetic protein-1

4. Disruption of the murine procollagen C-proteinase enhancer 2 gene causes accumulation of pro-apoA-I and increased HDL levels

5. Identification and Expression of a Novel Type I Procollagen C-Proteinase Enhancer Protein Gene from the Glaucoma Candidate Region on 3q21–q24

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