Cardiovascular diseases, such as stroke and heart attack, are one of the largest causes of death and morbidity in Canada. Atherosclerosis, or the thickening of the arterial wall, has been identified as the primary culprit lesion behind the end organ damage associated with cardiovascular diseases. Magnetic resonance imaging has taken a primary role in characterising the constituents of these atherosclerotic plaques. Of these components, MR detected intraplaque haemorrhage (IPH), or bleeding inside the vessel wall, appears to predispose a patient to future clinical events. This leads us to the conclusion that IPH is a secondary manifestation of plaque progression and complication, or somehow contributes to the complication of these atherosclerotic plaques. This thesis explores this second possibility, in line with the “iron hypothesis” of atherosclerosis which suggests that iron plays a significant, primary role in atherogenesis. In chapter two, the signal hyperintensity associated with IPH is correlated with the lipid oxidising potential of blood products in various oxidation states. It is found that the ferric paramagnetic species has a significantly greater ability to generate lipid oxide components and oxidise lipid surrogates. This finding suggests that it may be possible to alter the course of plaque progression by inhibiting the active ferric iron state. Chapter three explores an endogenous molecule, haptoglobin, whose purpose is to bind and inactivate free haemoglobin. It is shown that haptoglobin has the ability to modulate the MR signal intensity from IPH. Chapter four explores a mechanism to detect this imaging biomarker outside the MR environment using the electron paramagnetic resonance of the ferric haemoglobin. Results are shown in a custom made bench top system detecting ferric haemoglobin in an in vitro sample. This thesis provides more evidence for the iron hypothesis of atherosclerosis and explores methods of inhibiting and detecting this biomarker of disease.

Cardiovascular diseases, such as stroke and heart attack, are one of the largest causes of death and morbidity in Canada. Atherosclerosis, or the thickening of the arterial wall, has been identified as the primary culprit lesion behind the end organ damage associated with cardiovascular diseases. Magnetic resonance imaging has taken a primary role in characterising the constituents of these atherosclerotic plaques. Of these components, MR detected intraplaque haemorrhage (IPH), or bleeding inside the vessel wall, appears to predispose a patient to future clinical events. This leads us to the conclusion that IPH is a secondary manifestation of plaque progression and complication, or somehow contributes to the complication of these atherosclerotic plaques. This thesis explores this second possibility, in line with the “iron hypothesis” of atherosclerosis which suggests that iron plays a significant, primary role in atherogenesis. In chapter two, the signal hyperintensity associated with IPH is correlated with the lipid oxidising potential of blood products in various oxidation states. It is found that the ferric paramagnetic species has a significantly greater ability to generate lipid oxide components and oxidise lipid surrogates. This finding suggests that it may be possible to alter the course of plaque progression by inhibiting the active ferric iron state. Chapter three explores an endogenous molecule, haptoglobin, whose purpose is to bind and inactivate free haemoglobin. It is shown that haptoglobin has the ability to modulate the MR signal intensity from IPH. Chapter four explores a mechanism to detect this imaging biomarker outside the MR environment using the electron paramagnetic resonance of the ferric haemoglobin. Results are shown in a custom made bench top system detecting ferric haemoglobin in an in vitro sample. This thesis provides more evidence for the iron hypothesis of atherosclerosis and explores methods of inhibiting and detecting this biomarker of disease.