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2 H$ _{2}$ O-Based High-Density Lipoprotein Turnover Method for the Assessment of Dynamic High-Density Lipoprotein Function in Mice
| Content Provider | Scilit |
|---|---|
| Author | Kasumov, Takhar Willard, Belinda Li, Ling Li, Min Conger, Heather Buffa, Jennifer A. Previs, Stephen McCullough, Arthur Hazen, Stanley L. Smith, Jonathan D. |
| Copyright Year | 2013 |
| Description | Journal: Arteriosclerosis, thrombosis, and vascular biology Objective—: High-density lipoprotein (HDL) promotes reverse cholesterol transport from peripheral tissues to the liver for clearance. Reduced HDL-cholesterol (HDLc) is associated with atherosclerosis; however, as a predictor of cardiovascular disease, HDLc has limitations because it is not a direct marker of HDL functionality. Our objective was to develop a mass spectrometry–based method for the simultaneous measurement of HDLc and ApoAI kinetics in mice, using a single$ ^{2}$ H$ _{2}$ O tracer, and use it to examine genetic and drug perturbations on HDL turnover in vivo. Approach and Results—: Mice were given$ ^{2}$ H$ _{2}$ O in the drinking water, and serial blood samples were collected at different time points. HDLc and ApoAI gradually incorporated$ ^{2}$ H, allowing experimental measurement of fractional catabolic rates and production rates for HDLc and ApoAI. ApoE$ ^{−/−}$ mice displayed increased fractional catabolic rates ( P <0.01) and reduced production rates of both HDLc and ApoAI ( P <0.05) compared with controls. In human ApoAI transgenic mice, levels and production rates of HDLc and human ApoAI were strikingly higher than in wild-type mice. Myriocin, an inhibitor of sphingolipid synthesis, significantly increased both HDL flux and macrophage-to-feces reverse cholesterol transport, indicating compatibility of this HDL turnover method with the macrophage-specific reverse cholesterol transport assay. Conclusions—:$ ^{2}$ H$ _{2}$ O-labeling can be used to measure HDLc and ApoAI flux in vivo, and to assess the role of genetic and pharmacological interventions on HDL turnover in mice. Safety, simplicity, and low cost of the$ ^{2}$ H$ _{2}$ O-based HDL turnover approach suggest that this assay can be scaled for human use to study effects of HDL targeted therapies on dynamic HDL function. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3958961/pdf https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.113.301700 |
| Ending Page | 2003 |
| Page Count | 10 |
| Starting Page | 1994 |
| ISSN | 10795642 |
| e-ISSN | 15244636 |
| DOI | 10.1161/atvbaha.113.301700 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Issue Number | 8 |
| Volume Number | 33 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2013-08-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Arteriosclerosis, thrombosis, and vascular biology Endocrinology and Metabolism Peripheral Vascular Disease Mass Spectrometry Apolipoprotein A-i Protein Biosynthesis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cardiology and Cardiovascular Medicine |
