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Novel phosphatidylethanolamine derivatives accumulate in circulation in hyperlipidemic ApoE−/− mice and activate platelets via TLR2
| Content Provider | Scilit |
|---|---|
| Author | Biswas, Sudipta Xin, Liang Panigrahi, Soumya Zimman, Alejandro Wang, Hua Yakubenko, Valentin P. Byzova, Tatiana V. Salomon, Robert G. Podrez, Eugene A. |
| Copyright Year | 2016 |
| Description | A prothrombotic state and increased platelet reactivity are common in dyslipidemia and oxidative stress. Lipid peroxidation, a major consequence of oxidative stress, generates highly reactive products, including hydroxy-ω-oxoalkenoic acids that modify autologous proteins generating biologically active derivatives. Phosphatidylethanolamine, the second most abundant eukaryotic phospholipid, can also be modified by hydroxy-ω-oxoalkenoic acids. However, the conditions leading to accumulation of such derivatives in circulation and their biological activities remain poorly understood. We now show that carboxyalkylpyrrole-phosphatidylethanolamine derivatives (CAP-PEs) are present in the plasma of hyperlipidemic $ApoE^{−/−}$ mice. CAP-PEs directly bind to TLR2 and induces platelet integrin $α_{IIb}β_{3}$ activation and P-selectin expression in a Toll-like receptor 2 (TLR2)-dependent manner. Platelet activation by CAP-PEs includes assembly of TLR2/TLR1 receptor complex, induction of downstream signaling via MyD88/TIRAP, phosphorylation of IRAK4, and subsequent activation of tumor necrosis factor receptor–associated factor 6. This in turn activates the Src family kinases, spleen tyrosine kinase and PLCγ2, and platelet integrins. Murine intravital thrombosis studies demonstrated that CAP-PEs accelerate thrombosis in TLR2-dependent manner and that TLR2 contributes to accelerate thrombosis in mice in the settings of hyperlipidemia. Our study identified the novel end-products of lipid peroxidation, accumulating in circulation in hyperlipidemia and inducing platelet activation by promoting cross-talk between innate immunity and integrin activation signaling pathways. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882806/pdf |
| Ending Page | 2629 |
| Page Count | 12 |
| Starting Page | 2618 |
| DOI | 10.1182/blood-2015-08-664300 |
| Journal | Blood |
| Issue Number | 21 |
| Volume Number | 127 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2016-05-26 |
| Access Restriction | Open |
| Subject Keyword | Biochemistry and Molecular Biology Innate Immunity Stress Thrombosis Accumulate in Circulation Lipid Peroxidation Phosphatidylethanolamine Derivatives Inducing Platelet Journal: Blood (Vol- 134, Issue- 21) |
| Content Type | Text |
| Resource Type | Article |
