The influence of sleep and exercise on endothelial function and atherogenesis

Abstract

Mendelian randomization studies show causal associations between genetically predicted short sleep durations and atherogenesis. Engagement in exercise training, conversely, staves atherogenic adaptations by tempering myelopoiesis and preserving endothelial function. Sleeping patterns and exercise engagement therefore represent two critical lifestyle factors that can shape the human atherosclerotic landscape. The concomitant effect of these two lifestyle factors on atherogenesis within the same organism may elicit a net neutral response, or a response wherein hormetic stresses imposed by exercise exacerbate the atherogenic adaptations that are associated with shortened sleep. We performed several experiments to examine and enumerate the nature of these interactions, and hypothesized that greater cardiorespiratory fitness and exercise may mitigate negative adaptations associated with sleep disruption. In our first study (Chapter 2), we found that acute partial sleep deprivation did not alter endothelial function or arterial mechanics. Cardiorespiratory fitness, proxied by VO2peak, did not moderate the arterial responses associated with acute partial sleep restriction. Our second and third studies (Chapters 3 & 4) used experimental models of comparatively prolonged instances of perturbed sleep to show that endothelial dysfunction induced by perturbed sleep was only partially reversed by engagement in voluntary exercise. We also found evidence to suggest that exercise did not reverse a mildly inflamed and metabolically-dysregulated circulatory milieu that was imparted by curtailed sleep. Rather, our data suggest that interactions between disrupted sleeping patterns and arterial function may be mediated by shear stress and associated hemodynamic forces experienced by the vasculature. In study four (Chapter 5), we enumerated the hemodynamic shear waveform patterns that may confer atheroprotection. We decomposed shear rate waveforms to find that increased amplitudes of lower frequency shear spectra associated with improved measures of endothelial function across multiple experimental paradigms. This thesis adds to a growing body of research that suggests atherogenic adaptations may be controlled by interactions between arterial hemodynamics and lifestyle factors. We propose directions for future research that may employ stringent standardization and higher temporal resolution around outcome measures to further enumerate the interactions between sleeping patterns and exercise on cardiovascular control.