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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Browning, Jeffrey D. Horton, Jay D. |
| Description | Country affiliation: United States Author Affiliation: Browning JD ( Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. jeffrey.browning@utsouthwestern.edu) |
| Abstract | Proprotein convertase, subtilisin/kexin type 9 (PCSK9), a key regulator of plasma LDL-cholesterol (LDL-c) and cardiovascular risk, is produced in liver and secreted into plasma where it binds hepatic LDL receptors (LDLR), leading to their degradation. PCSK9 is transcriptionally activated by sterol response element-binding protein (SREBP)-2, a transcription factor that also activates all genes for cholesterol synthesis as well as the LDLR. Here we investigated the relationship between plasma PCSK9 levels and the lathosterol-to-cholesterol ratio, a marker of cholesterol biosynthesis, in 18 healthy subjects during a 48 h fast. In all individuals, plasma PCSK9 levels declined steadily during the fasting period, reaching a nadir at 36 h that was â¼58% lower than levels measured in the fed state (P < 0.001). Similarly, the lathosterol-to-cholesterol ratio declined in parallel with plasma PCSK9 concentrations during the fast, reaching a nadir at 36 h that was â¼28% lower than that measured in the fed state (P = 0.024). In summary, fasting has a marked effect on plasma PCSK9 concentrations, which is mirrored by measures of cholesterol synthesis in humans. Inasmuch as cholesterol synthesis and PCSK9 are both regulated by SREBP-2, these results suggest that plasma PCSK9 levels may serve as a surrogate marker of hepatic SREBP-2 activity in humans. |
| File Format | HTM / HTML |
| ISSN | 00222275 |
| e-ISSN | 15397262 |
| DOI | 10.1194/jlr.P009860 |
| Journal | The Journal of Lipid Research |
| Issue Number | 11 |
| Volume Number | 51 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2010-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Biochemistry Cholesterol Biosynthesis Fasting Blood Serine Endopeptidases Adolescent Hypercholesterolemia Drug Therapy Metabolism Proprotein Convertases Clinical Trial Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Endocrinology |
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