Third-Hand Smoke Impact on Platelet Function and Thrombosis
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abstract
While the involvement of the well-known first-hand smoke (FHS) and second-hand smoke (SHS) in the pathogenesis of thrombotic diseases is well documented, the contribution of the newly “discovered” third-hand form (THS) in such disease processes remains unknown. This derives, in part, from: (1) initial lack of knowedlge of THS existence; (2) lack of appreciation for its “real” negative health consequences; (3) lack of a THS-exosure animal model; and (4) lack of studies regarding such consequences on platelet biology. The present application proposes experiments that address fundamental, mechanistic and clinically-relevant translational aspects of the adverse-health effects of the newly “realized” form of smoking, THS, in the context of thrombotic disease and platelet biology. The present application proposes experiments that address fundamental and mechanistic aspects of the toxicity of Third-Hand Smoke (THS), namely its ability to modulate platelet function and related disorders; platelets are known to play critical roles in the pathogenesis of multiple tobacco-associated thrombotic disorders. Thus, we should not only learn about the negative effects of THS, but also better understand mechanistically how those effects are exerted on the cardiovascular system. The outcome of these studies may also result in new or better ways for managing smoking induced platelet-dependent diseases. The Aims of our proposal are:Aim 1. Investigate the impact of THS-exposure on platelet-dependent disease states. While compelling recent evidence revealed that exposure to THS does exert negative health effects, its impact on platelet-dependent diseases is still unknown. To address this issue, we will determine the ramifications of THS exposure on normal hemostasis and platelet counts, in a dose-, and time-dependent fashion. Subsequent studies will examine whether THS participates in the development of thrombosis-based disease. Nonetheless, our preliminary data revealed that THS does increased the risk of thrombosis. Aim 2. Investigate the mechanism by which THS-exposure modulates platelet function. Our preliminary data shows, for the first time, that THS modulates physiological hemostasis, suggesting that it may increase the risk of cardiovascular disease. However, the mechanism by which THS modules platelet function remains to be investigated. Thus, the overall goal of the experiments proposed in this section is to determine the significance of THS-exposure on a host of platelet functional responses and markers. It is noteworthy that our preliminary data shows that THS does enhance platelet aggregation, in response to the agonist ADP.Collectively, these experiments will make significant contributions to our understanding of the consequences of THS exposure on platelet activation and cardiovascular human health, and the mechanism by which THS exert its effects. It is expected that those studies will inform the public of the seriousness of THS exposure, guide policy for effective control & prevention measures, and may lay down the foundation for better therapeutic approaches for managing THS-dependent thrombosis, such as that seen in heart attacks.
