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In vitro and in vivo vascular response to exercise-induced changes in blood flow

Primary Supervisor: Dr Sam Lucas, School of Sport, Exercise and Rehabilitation Sciences

Secondary supervisor: Dr Helen McGettrick

PhD project title: In vitro and in vivo vascular response to exercise-induced changes in blood flow.

University of Registration: University of Birmingham

Project outline:

The global population is ageing and becoming increasingly sedentary, both of which have negative implications for vascular health. Interventions that target vascular function have the potential to protect against age-related cognitive decline, prevent stroke and lower the risk of neurovascular and cardiovascular disease, thus reducing the global economic burden associated with an ageing population and sedentary lifestyle. Traditionally, vascular function has been treated by medication, however non-clinical strategies can also be implemented, including the use of supplements, improved diet and increased regular exercise, often delivered collectively in the form of ‚Äúlifestyle interventions‚ÄĚ. Improved understanding of how such lifestyle interventions facilitate better function is vital for optimising their effectiveness.

Specifically, exercise has been shown to stimulate beneficial changes to the vasculature, through acute responses in nitric oxide bioavailability, growth factor release and anti-inflammatory effects. Chronically this results in improved vascular function, vasodilatory capacity and reduced vascular inflammation, all of which positively influence general vascular health and disease prognosis. Although increased physical activity, in general, has a beneficial impact on vascular health, how different exercise intensities and modalities influence the adaptive response via variations in blood flow-induced adaptive signalling (e.g. shear stress and cyclic strain) are poorly understood1. Further, adjunct approaches (e.g. exercise under added environmental stress (e.g. hydrostatic) and/or nutraceutical supplementation) may provide more targeted interventions that could optimise the exercise-induced adaptive response, especially for those unable to meet traditional exercise recommendations2. To support such initiatives, clear mechanistic evidence of the key signalling responses and biomarkers of change is vital.

This project will aim to identify the differences in cerebral and peripheral vascular function during exercise at different intensities and with different environmental conditions, whilst assessing the impact this has on key signalling, inflammatory and vasodilatory factors. Building on recent work3, the first of these studies will determine the effects of different exercise intensity and duration on cerebrovascular responses, along with the signalling and inflammatory responses that occur in response to exercise. We will then investigate whether differences in the exercise response are seen between younger and older populations, as well as how changes in environmental conditions may alter the exercise-induced vascular response.

This project will also utilise our in vitro shear stress model to further understanding of the impact of different shear stress profiles elicited from different exercise stimuli at the cellular level. To date, few studies have examined exercise-induced shear stress beyond that of a single flow pattern on the acute endothelial response. To address this, we are establishing a model that can be maintained within an incubator for a prolonged period, and which can emulate a wide range of different flow patterns in order to translate the differences we observed within human studies. This model will provide a platform for rapidly testing the impact of different environmental factors and media additives in future studies. Flow patterns from this project will contribute to this model development.

References:

  1. Lucas et al., (2015). High intensity exercise and cerebrovascular health; curiosity, cause and consequence. Journal of Cerebral Blood Flow and Metabolism, 35(6):902-11.
  2. Burley et al (2016). Brain train to combat brain drain; focus on exercise strategies that optimise neuroprotection. Experimental Physiology, 101 (9), 1178-1184.
  3. Weaver et al. (2021) Cerebral Hemodynamic and Neurotrophic Factor Responses Are Dependent on the Type of Exercise. Front. Physiol.11:609935. doi: 10.3389/fphys.2020.609935

BBSRC Strategic Research Priority: Integrated Understanding of Health: Ageing

Techniques that will be undertaken during the project:

  • Cell culture and flow-simulation
  • Prototyping and equipment development
  • Signal processing and simulation (advanced programming skills)
  • Microscopy and image analysis
  • Western Blotting
  • ELISA
  • Rt-qPCR
  • Mass spectroscopy
  • Exercise Testing (VO2max, respiratory gas analysis)
  • Blood testing (lactate, circulating NAD, NO and nitrite/nitrate, cytokines)
  • Doppler ultrasound (transcranial Doppler and Duplex)
  • Near infrared spectroscopy (NIRS) imaging
  • Functional vascular response testing (e.g. flow-mediated dilation)

Contact: Dr Sam Lucas, University of Birmingham