Research Project
10251078
Emerging evidence indicates that electronic cigarettes (e-cigs) induced significant, and similar, harm to the blood vessel structure and function as that seen with smoking. Nevertheless, e-cigs are being aggressively publicized as a healthier alternative to smoking and suggested as a medical aid for smoking cessation by health care providers ? even in the context of pregnancy. Given that cardiovascular disease (CVD) is the leading cause of death in the US (and worldwide), characterizing the toxicity and understanding the etiology of e-cig induced vascular dysfunction is critically important. The concern for maternal vaping and vascular health is also a significant issue, because, 1) the fetus is at a vulnerable period in life and 2) maternal inhalation of nearly any xenobiotic particulate matter is found to have adverse fetal/offspring developmental outcomes. Thus, there is a critical need for preclinical studies to examine the toxicity of vaping on vascular related outcomes. Current knowledge gaps relating to the toxicity potential of vaping include, 1) what effect does e-cig device settings (i.e. watts/temperature) have on toxicity potential relating to particle size and composition/concentration of chemical compounds generated; 2) what component(s) in the base solution contribute to development of vascular dysfunction; and 3) what are the long-term consequences of maternal vaping on offspring health and disease later in life? The goal of this proposal is to, 1) identify the relationship between the operating wattage/temperature of e-cigs on the particulate matter (PM) size distribution and chemical composition in association clinical/biological assessments of vascular function due to direct exposure (primary user) and indirect exposure (offspring health as consequence of maternal exposure during pregnancy). Our overarching hypothesis is that operating e-cig device at lower wattages/temperature increases the potential for vascular harm/impairment to user; and in the context of maternal vaping during pregnancy, will result in a hostile gestational environment that will lead to abnormal developmental programming that manifest as impaired cerebral vascular function and deficits in neurocognitive function compared to controls. Vascular toxicity effects will be determined by indices of arterial stiffness, vascular reactivity, and neurocognitive function, in relationship to altered physical-chemical exposures we generate. We expect our data will provide toxicological and clinical evidence to inform clinicians and consumers about vascular health concerns, and provide regulatory and federal agencies information needed in establishing public policy, guidelines or regulations.
