Physiological Basis of Low Frequency Oscillations in Endothelial Cells
Supervisor: Dr Jane Owen-Lynch
Many biological processes are oscillatory in nature, and some of them are far more subtle than the obvious ones like heartbeat, or respiration, or the diurnal cycle. It is now well-established that there are at least 6 oscillatory processes involved in the dynamics of blood flow, all operating at different frequencies. These oscillations can be measured non-invasively by laser Doppler flow metric analysis of blood flow or from other measurements in e.g. blood pressure, heart rate variability (HRV) extracted from the electrocardiogram and respiration. There is already clear evidence for definite changes in the pattern and coupling of oscillatory behaviour in several different clinical states and pathologies. Our recent work has extended this to demonstrate that aging results in a significant alteration of the relative contributions of the oscillatory components in the dynamics of blood flow. In particular, our data show that there is a marked change in blood flow dynamics associated with oscillatory activity of the low frequency components (linked to endothelial cells) with age. Although the wealth of evidence points to the low frequency components of blood flow dynamics being associated with endothelial cells, very little is known about the mechanism of generating these oscillations and the age related changes in these mechanisms. The aim of this project is to identify the component oscillatory mechanisms in the endothelial cells and thus begin to identify the key age related changes. The project will involve analysis of the regulation and activity of signalling pathways and ion movements in individual cells and monolayers of endothelial layers in response to fluid flow, vasodilatory and other pharmacological agents. The project will also require some work at the macroscopic level to use wavelet analysis of the LDF signals to provide more detailed information of the effects of age on blood flow dynamics.