Abstract 309: The Role of TLT-1 in Atherosclerosis Lesion Formation

Abstract

Platelets have a well documented role in atherosclerotic lesion formation. They play a role from the initiation of the lesion to final occlusion of an atherosclerotic vessel. While it is known that regulating aggregation is important to control the thrombus that leads to occlusion, the platelet’s role in promoting lesion formation is less defined. Molecules stored in the platelet a-granules such as p-selectin and cytokines, which promote the inflammatory side of platelet function, have been shown to affect lesion progression. These molecules, however, only provide an outline of the platelet function during this process. and thus our understanding of how platelets participate in the progression of atherosclerosis remains a gap in our knowledge. The Triggering Receptor Expressed Myeloid cells (TREM)-like transcript (TLT)-1 is a receptor found in the α-granules of both megakaryocytes and platelets. Antibodies to TLT-1 have been shown to inhibit platelet aggregation and accordingly studies using the treml1 -/- mouse have demonstrated that TLT-1 null mice have reduced platelet aggregation and extended tail-bleeding times. Subsequent studies using the treml1 -/- mouse demonstrated a predisposition to hemorrhage derived from an inflammatory challenge suggesting that TLT-1 may be a key regulatory molecule in the interface between hemostatic and inflammatory mechanisms. Additionally, apoE null mice have significantly higher levels of the soluble form of TLT-1 (sTLT-1) in their plasma compared to wild type mice suggesting that sTLT-1 may play a role in the progression of atherosclerotic lesions. Therefore, we hypothesized that removal of TLT-1 receptor will delay the formation of atherosclerotic lesions in an apoE deficient genetic background. To address our hypothesis, we have created an apoE/treml1 double null mouse and investigated the development of lesions in the aortic sinus. Our preliminary data show an unexpected trend where the lesions in apoE/treml1 double null mice have exacerbated compared to apoE or treml1 -/- mice suggesting that TLT-1 may actually have a anti-inflammatory effect during the progression of atherosclerosis. The status of the current research will be presented here.