Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the Western world. Recent epidemiological studies suggest that conditions within the fetal environment and adult CVD are linked. Nevertheless, studies demonstrating a clear relationship between fetal exposures and adult CVD are lacking. While the precise sequence of events that lead to CVD are not fully elucidated, oxidative stress mediated by metabolic defects and, importantly, environmental insults play a significant role in atherogenesis. Importantly, environmental tobacco smoke (ETS) is a ubiquitous toxicant that induces oxidative stress and promotes CVD. However, the impacts of maternal-fetal ETS exposure on adult atherosclerotic disease development remain equivocal. Mitochondria are important cellular organelles with critical functions related to energy production, programmed cell death, growth, and redox signaling. We have previously demonstrated that: 1) CVD risk factors (including ETS) promote both mitochondrial damage and atherogenesis, 2) mitochondrial dysfunction and oxidative stress hastens atherogenesis, and 3) fetal ETS exposure increases adult atherogenesis and mitochondrial damage. Consequently, we hypothesize that: Fetal ETS exposure will result in significant mitochondrial damage, dysfunction, and atherogenesis in adult offspring, thereby promoting adult CVD. To test this hypothesis, three specific aims are submitted that will: 1) Determine the effects of fetal ETS exposure on adult atherosclerotic lesion development and cardiovascular mitochondrial damage in mice.2) Determine the effects of fetal ETS exposure on mitochondrial function and proteins in adult mice. 3) Quantify the impact of altered mitochondrial oxidative stress on adult atherogenesis consequent to fetal ETS exposure. These studies will provide novel insights regarding the impact of fetal ETS exposure on adult atherogenesis and mitochondrial function. Moreover, the potential long term health consequences of fetal ETS exposure on adult CVD development will be defined. ? ?
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