Investigation of the Mechanistic Impact of Prenatal Exposure to Thirdhand Smoke on Platelet Activation

Abstract

Cigarette smoking is a major risk factor for acute coronary thrombosis. In fact, both active/first hand smoke (FHS) and passive/second hand smoke (SHS) exposure-including that which is in utero- are known to increase the risk of coronary thrombosis. While recently a new risk has been identified and termed third hand smoke (THS)-which is the residual tobacco smoke contaminant that remains after a cigarette is extinguished- it remains to be determined whether in utero THS can also enhance the risk of thrombogenesis, much like FHS and SHS. Therefore, the present studies investigated the impact of in utero THS exposure in the context of platelet biology and related disease states. It was found that THS-exposed mice exhibited an enhanced platelet aggregation, and secretion responses. In utero THS was also found to enhance GPIIb/IIIa activation and phosphatidylserine exposure. Furthermore, and as for its in vivo impact, it was found that in utero THS exposure shortens the tail bleeding time, as well as the occlusion time in a model of thrombosis. Cytokine analysis revealed serum IL-9 downregulation and lung IL-5 upregulation in the THS exposed mice, which indicates impaired tissue repair and increased asthma risk, respectively. Thus, our data demonstrate for the first time that in utero THS exposure increases the risk of thrombosis-based disease states, which is attributed, at least in part, to their hyperactive platelets. Thus, the negative health consequences of THS should not be underestimated, and warrant further investigation. These findings should guide policy development for regulating exposure to this form of tobacco.