MARKERS OF CARDIOVASCULAR DYSFUNCTION AFTER PREGNANCIES COMPLICATED BY PRE-ECLAMPSIA

Pre-eclampsia (PE) is a hypertensive disorder of pregnancy characterized by maternal systemic endothelial dysfunction. While the clinical manifestations resolve soon after delivery, a large body of epidemiological evidence indicates significant long-term maternal risk for cardiovascular disease (CVD) after PE. The mechanisms by which PE and future CVD are associated are unclear, although shared constitutional risk factors likely contribute to the features of endothelial dysfunction characteristic to both. We postulate that PE offers a window of opportunity for the identification of unique markers of dysfunction in the earliest stages of disease that may be used to validate cardiovascular risk screening in the early postpartum period. The studies presented in this thesis provide evidence of changes in circulating factors in women with a recent history of PE. Using blood samples collected within the first year of pregnancy, unique patterns of microRNA expression, enrichment of coagulation system proteins and endothelial progenitor cell dysfunction were described. Many of the described changes appear to be independent of cardiovascular risk. In addition to alterations in circulating factors however, longitudinal postpartum assessments demonstrated that microvascular and cardiac abnormalities were evident in the early periods postpartum after a pre-eclamptic pregnancy. Collectively, the data presented in this thesis reveal that physiological alterations in women with a recent history of PE are not necessarily dependent on clinical parameters of cardiovascular risk, and that resulting dysfunction may be demonstrated within the first year postpartum. Importantly, the biomarkers presented herein are all demonstrated elsewhere in the literature to benefit from lifestyle modification and risk reduction. In closing, the findings of this thesis support a need for cardiovascular risk screening based on obstetrical history, namely after pregnancies complicated by PE.

Do protected areas mitigate the effects of fisheries-induced evolution on parental care behaviour of a recreationally-important teleost fish?

Human-induced selection on animals and plants has been highly influential throughout our history and resulted in both intentional benefits and unintended detriments. Fisheries-induced evolution (FIE) describes the unintended selection on wild fish populations by fishing that has resulted in the evolution of exploited populations. While the use of aquatic protected areas that exclude angling might be considered an evolutionarily-enlightened management approach to dealing with issues arising from FIE little is known about the effectiveness of this approach for maintaining the phenotypic diversity of traits in protected areas versus those outside of their boundaries. In species that exhibit parental care, including the largemouth bass (Micropterus salmoides), active nest guarding and aggression towards potential brood predators by males increases the survival of offspring. This aggression may render these individuals particularly vulnerable to capture via angling as a result of increased propensity to attack fishing lures near their nests. Relative levels of aggression by these males during the parental care period correlate with their vulnerability to angling year round. Inasmuch as this parental behavior is heritable, this selective removal of more aggressive individuals by anglers should drive population-average phenotypes towards lower levels of aggression. To assess the effectiveness of protected areas at mitigating FIE, I compared the nest guarding behaviours of wild, free-swimming male bass during the early nesting period for bass within and outside protected areas. I found that nesting males within long-standing fishing sanctuaries (>70 yrs) were more aggressive towards captive bluegill sunfish (Lepomis macrochirus) placed directly on their nests, and patrolled larger areas around their nests compared to bass outside of sanctuaries. Males within protected areas were more likely to strike at artificial fishing lures and more prone to capture during experimental angling events. Collectively, my findings suggest that recreational angling selects for individual bass with lower levels of parental care and aggression, and that the establishment of protected areas may mitigate potential FIE. The extent to which this phenomenon occurs in other species and systems likely depends on the reproductive strategies of the fishes being considered, their spatial ecology relative to sanctuary boundaries, and habitat quality within protected areas.

The adaptive response of humans to exercise: Impact of exercise intensity, fibre-type specific responses and molecular patterns of response

In an attempt to improve the current understanding of the adaptive response to exercise in humans, this dissertation performed a series of studies designed to examine the impact of training intensity and mode on aerobic capacity and performance, fibre-type specific adaptations to training, and individual patterns of response across molecular, morphological and genetic factors. Project #1 determined that training intensity, session dose, baseline VO2max and total training volume do not influence the magnitude of change in VO2max by performing a meta-regression, and meta-analysis of 28 different studies. The intensity of training had no effect on the magnitude of increase in maximal oxygen uptake in young healthy participants, but similar adaptations were achieved with lower training doses following high intensity training. Project # 2 determined the acute molecular response, and training-induced adaptations in aerobic performance, aerobic capacity and muscle phenotype following high-intensity interval training (HIT) or endurance exercise (END). The acute molecular response (fibre recruitment and signal activation) and training-induced adaptations in aerobic capacity, aerobic performance, and muscle phenotype were similar following HIT and END. Project # 3 examined the impact of baseline muscle morphology and molecular characteristics on the training response, and if muscle adaptations are coordinated. The muscle phenotype of individuals who experience the largest improvements (high responders) were lower before training for some muscle characteristics and molecular adaptations were coordinated within individual participants. Project # 4 examined the impact of 2 different intensities of HIT on the expression of nuclear and mitochondrial encoded genes targeted by PGC-1α. A systematic upregulation of nuclear and mitochondrial encoded genes was not present in the early recovery period following acute HIT, but the expression of mitochondrial genes were coordinated at an individual level. Collectively, results from the current dissertation contribute to our understanding of the molecular mechanisms influencing skeletal muscle and whole-body adaptive responses to acute exercise and training in humans.