The characterization of the TLT-1 soluble fragment and the evaluation of TLT-1 as a biomarker for cardiovascular diseases and acute respiratory distress syndrome
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Author
Bayrón Marrero, Zaida I
Advisor
Washington, ValanceType
ThesisDegree Level
M.S.Date
2022-08-23Metadata
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Platelets are anucleate cells produced in the bone marrow that are responsible for coagulation. Various platelets agonists activate platelets including thrombin generated from the clotting cascade, collagen from the sub-endothelium and ADP released from the platelets themselves. This triggers the formation of a fibrin(ogen) web; this web formation was attributed for years to the integrin IIb IIIa. But recently, a new fibrinogen binding partner was identified called the Triggering Receptor Express on Myeloid Cells (TREM) – like transcript 1 (TLT-1). TLT-1 facilitates platelet aggregation and mediates thrombus formation. The soluble form has the potential to be a marker for severe diseases. Elevated sTLT-1 plasma levels are associated with chest pain with cardiovascular origin and our lab demonstrated TLT-1 and its soluble form, sTLT-1, have a major role in the progression of acute respiratory distress syndrome. Our objectives were to better characterize the constituent amino acids of sTLT-1 and evaluate sTLT-1 for use as a biomarker in coronary artery diseases and to determine if platelet positive TLT-1 microparticles in patients with acute respiratory distress syndrome can be used as a marker for disease severity. Our studies revealed that TLT-1 is cleaved after amino acid 136 when TLT-1 is cleaved by ADAMs17. Our evaluation of sTLT-1 in a cohort of 1510 patients with stable cardiovascular disease that elevated levels of sTLT-1 suggest a risk of congestive heart failure triggered by abnormal left ventricular function. Finally, we found that higher levels TLT-1 positive particles correlate with decreased survival, and longer hospital stays in patients with acute respiratory distress syndrome.