Clinical analysis of Trem-Like Transcript-1 in large cohorts of patients from the NHLBI Biorepository

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Abstract Triggering receptor expressed in Myeloid cells (TREM) Like transcript (TLT)-1 is a prominent platelet receptor stored in the -granules of platelets. While it is virtually absent on the surface resting platelets, it highly expressed on the surface of activated platelets and released as a soluble fragment (sTLT-1). TLT-1 binds to neutrophils and endothelial cells. During acute inflammation it mediates smooth leukocyte transmigration out of the vessels protecting the vessels from excessive bleeding. The effect is particularly prominent in the lungs. TLT-1 interaction with endothelial cells initiates cell growth and proliferation and when targeted in a Lewis lung carcinoma model displays anti-angiogenic properties. As such our studies have defined roles for TLT-1 in acute lung inflammation, atherosclerosis, and cancer. Here we propose to clinically translate our findings using the rich resource presented by the NIH biorepository. We will investigate samples from ARDS patients to find clinical correlation of TLT-1 positive microparticles with the mortality and hospital stay. We will evaluate samples from cardiovascular patients in the PEACE study for correlations of the soluble fragment and TLT-1 positive microparticles with adverse cardiac events..