Sex Dependent Occlusive Cardiovascular Disease Effects of Short-Term Thirdhand Smoke Exposure

Nicotine Tob Res. 2024 Mar 23:ntae061. doi: 10.1093/ntr/ntae061. Online ahead of print.

Abstract

Introduction: Thirdhand smoke (THS) is associated with many public health and disease concerns, such as respiratory illness, cancer, lipidemia, and cardiovascular disease (CVD). We have previously shown a moderate to long-term exposure to THS increased risk of thrombosis. However, whether short-term exposure to THS would produce any effects in causing disease remains to be discovered. Therefore, this study investigated the impact of one-month THS exposure on platelet function and cytokine response in sex-dependent.

Methods: Secondhand smoke or clean air (CA) exposed upholstery materials for 1 week were kept in cages housed with 5-6 mice, and the procedure was repeated for 4 weeks. These THS-exposed mice were evaluated for thrombogenesis and platelet function assays. In addition, the cytokines expressions were evaluated from pooled serum (n=5).

Results: Compared to the CA group, the THS exposure significantly shortened tail bleeding time and carotid artery thrombus formation. Moreover, the female mice appeared more sensitive to THS exposure than males. Furthermore, platelet aggregation, dense granule secretion, and P-selectin activation markers were significantly elevated due to THS exposure. In addition, the high throughput screening showed at least 30 cytokines differentially modulated by THS in females relative to 26 in male mice.

Conclusion: Collectively, these results demonstrate that one month of THS exposure represents a high health risk, in part, by triggering a prothrombotic phenotype that appears to be more significant in females, who are at a much higher risk for occlusive CVD. Additionally, changes in cytokine levels mediate some of the THS-induced occlusive effects.

Implications: This study revealed that THS exposure in one month is detrimental to the cardiovascular health of both sexes; however, females could be more aggressively affected than males. In addition, interleukins and chemokines could be critical factors for initiating prothrombotic activity due to THS exposure.

Keywords: hemostasis; platelet; thirdhand smoke; thrombosis.