UC Davis

While the incidences of cardiovascular diseases declined by 27% over the past few decades, the number of deaths related to cardiovascular diseases increased by 42%, owing to the population growth and increased life expectancy. Consequently, cardiovascular diseases are the leading cause of death worldwide. Cardiovascular diseases are complex, multifactorial diseases that cannot be ascribed to a single risk factor. Secondhand smoke (SHS) and high-fat diet (HFD) are two preventable risk factors for the development and progression of cardiovascular diseases. Interestingly, epidemiological studies have correlated SHS exposure with poor dietary habits including higher total fat intakes, suggesting an underestimated incidences of co-exposure of SHS and HFD worldwide. In this study, we sought to characterize the effects of SHS, at an environmentally relevant concentration, on cardiovascular regulation, and the time-course of SHS-induced cardiovascular changes using a mouse model (chapter 2). We also assessed the effects of long-term consumption of HFD on heart rate (HR) and blood pressure (BP) regulation in mice (chapter 3). Moreover, this work aimed to investigate the effects of SHS and HFD co-exposure on cardiovascular function (chapter 3).

To test these aims, mice implanted with BP/ electrocardiogram (ECG) telemetry devices were fed with either standard rodent chow (13.6 kcal% fat) or HFD (60 kcal% fat) and exposed to either filtered air (FA) or SHS (3 mg/m3, 6 hours/day, 5 days/week). BP, HR, HR variability (HRV), BP variability, and baroreflex sensitivity (BRS) were obtained to evaluate the cardiovascular function.

We found that long-term exposure of SHS decreased measures of autonomic regulation of HR (HRV) and BP (BRS), as well as decreased pulse pressure (PP) in a time-dependent manner. The effects of SHS on PP and HRV had a faster onset that observed after four weeks of exposure, while the effects of SHS on BRS had a slower onset and accumulated with longer exposure time. However, all SHS-induced cardiovascular dysfunctions recovered after removal from SHS exposure for four weeks. Long-term exposure of HFD alone increased weight gain, increased BP, and reduced BRS and HRV. Strikingly, we found that co-exposure of SHS and HFD significantly increased BP variability that was not observed with SHS or HFD alone, suggesting a co-exposure-induced BP dysregulation.

Overall, this study demonstrated that chronic exposure to SHS and HFD both reduces the autonomic regulation of the cardiovascular function. Co-exposure of SHS and HFD can interactively induce BP dysregulation, which may put individuals under even higher risks of cardiovascular morbidity and mortality. This study provides insights into the importance of understanding the interplay between multiple risk factors in inducing cardiovascular dysfunctions when studying the multifactorial cardiovascular diseases.