Loading...
Please wait, while we are loading the content...
Similar Documents
Blockade of Tim-1 and Tim-4 Enhances Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient Mice
| Content Provider | Scilit |
|---|---|
| Author | Foks, Amanda C. Engelbertsen, Daniel Kuperwaser, Felicia Alberts-Grill, Noah Gonen, Ayelet Witztum, Joseph L. Lederer, James Jarolim, Petr DeKruyff, Rosemarie H. Freeman, Gordon J. Lichtman, Andrew H. |
| Copyright Year | 2016 |
| Description | Journal: Arteriosclerosis, thrombosis, and vascular biology Objective—: T cell immunoglobulin and mucin domain (Tim) proteins are expressed by numerous immune cells, recognize phosphatidylserine on apoptotic cells, and function as costimulators or coinhibitors. Tim-1 is expressed by activated T cells but is also found on dendritic cells and B cells. Tim-4, present on macrophages and dendritic cells, plays a critical role in apoptotic cell clearance, regulates the number of phosphatidylserine-expressing activated T cells, and is genetically associated with low low-density lipoprotein and triglyceride levels. Because these functions of Tim-1 and Tim-4 could affect atherosclerosis, their modulation has potential therapeutic value in cardiovascular disease. Approach and Results—: ldlr$ ^{−/−}$ mice were fed a high-fat diet for 4 weeks while being treated with control (rat immunoglobulin G1) or anti-Tim-1 (3D10) or -Tim-4 (21H12) monoclonal antibodies that block phosphatidylserine recognition and phagocytosis. Both anti-Tim-1 and anti-Tim-4 treatments enhanced atherosclerosis by 45% compared with controls by impairment of efferocytosis and increasing aortic CD4$ ^{+}$ T cells. Consistently, anti-Tim-4-treated mice showed increased percentages of activated T cells and late apoptotic cells in the circulation. Moreover, in vitro blockade of Tim-4 inhibited efferocytosis of oxidized low-density lipoprotein–induced apoptotic macrophages. Although anti-Tim-4 treatment increased T helper cell (Th)1 and Th2 responses, anti-Tim-1 induced Th2 responses but dramatically reduced the percentage of regulatory T cells. Finally, combined blockade of Tim-1 and Tim-4 increased atherosclerotic lesion size by 59%. Conclusions—: Blockade of Tim-4 aggravates atherosclerosis likely by prevention of phagocytosis of phosphatidylserine-expressing apoptotic cells and activated T cells by Tim-4-expressing cells, whereas Tim-1-associated effects on atherosclerosis are related to changes in Th1/Th2 balance and reduced circulating regulatory T cells. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4853762/pdf https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.115.306860 |
| Ending Page | 465 |
| Page Count | 10 |
| Starting Page | 456 |
| ISSN | 10795642 |
| e-ISSN | 15244636 |
| DOI | 10.1161/atvbaha.115.306860 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Issue Number | 3 |
| Volume Number | 36 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2016-03-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Arteriosclerosis, thrombosis, and vascular biology Peripheral Vascular Disease |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cardiology and Cardiovascular Medicine |
