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*
| Autor: | Ricquita D. Pollard, Mary G. Sorci-Thomas, Xiang-An Li, Mark Gerelus, Xuewei Zhu, Nebil Nuradin, Daisy Sahoo, Michael J. Thomas, Christopher N. Blesso, Brian Fulp, Manal Zabalawi, Omar L. Francone, Erica W. Lyons |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Apolipoprotein B Antigens Differentiation Myelomonocytic Biological Transport Active CHO Cells Biology Biochemistry chemistry.chemical_compound Mice High-density lipoprotein Cricetulus Antigens CD Internal medicine medicine Animals Humans Scavenger receptor Molecular Biology Aorta Glycoproteins Mice Knockout Apolipoprotein A-I Cholesterol Macrophages Reverse cholesterol transport Intracellular Signaling Peptides and Proteins nutritional and metabolic diseases Cell Biology Scavenger Receptors Class B Atherosclerosis Procollagen peptidase Endocrinology Metabolism chemistry Receptors LDL LDL receptor Cholesteryl ester biology.protein lipids (amino acids peptides and proteins) Cholesterol Esters Lipoproteins HDL |
| Popis: | Studies in human populations have shown a significant correlation between procollagen C-endopeptidase enhancer protein 2 (PCPE2) single nucleotide polymorphisms and plasma HDL cholesterol concentrations. PCPE2, a 52-kDa glycoprotein located in the extracellular matrix, enhances the cleavage of C-terminal procollagen by bone morphogenetic protein 1 (BMP1). Our studies here focused on investigating the basis for the elevated concentration of enlarged plasma HDL in PCPE2-deficient mice to determine whether they protected against diet-induced atherosclerosis. PCPE2-deficient mice were crossed with LDL receptor-deficient mice to obtain LDLr(-/-), PCPE2(-/-) mice, which had elevated HDL levels compared with LDLr(-/-) mice with similar LDL concentrations. We found that LDLr(-/-), PCPE2(-/-) mice had significantly more neutral lipid and CD68+ infiltration in the aortic root than LDLr(-/-) mice. Surprisingly, in light of their elevated HDL levels, the extent of aortic lipid deposition in LDLr(-/-), PCPE2(-/-) mice was similar to that reported for LDLr(-/-), apoA-I(-/-) mice, which lack any apoA-I/HDL. Furthermore, LDLr(-/-), PCPE2(-/-) mice had reduced HDL apoA-I fractional clearance and macrophage to fecal reverse cholesterol transport rates compared with LDLr(-/-) mice, despite a 2-fold increase in liver SR-BI expression. PCPE2 was shown to enhance SR-BI function by increasing the rate of HDL-associated cholesteryl ester uptake, possibly by optimizing SR-BI localization and/or conformation. We conclude that PCPE2 is atheroprotective and an important component of the reverse cholesterol transport HDL system. |
| Databáze: | OpenAIRE |
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