Grant: Master's Award: Canada Graduate Scholarships

The response to vascular injury involves the transition of the normal, differentiated vascular smooth muscle cells (VSMCs) to a proliferative, dedifferentiated form with decreased contractile filaments. The subsequent VSMC proliferation induce irreversible lesions which provide obstruction for blood flow.Hypothesis and objectiveOur objective is to investigate the impact cardiolipin has on the VSMC phenotype shift and whether these modifications are mediated through VSMC mitochondria. Experimental approach Early changes leading to phenotype shift are studied using vessel organ culture model to allow maintenance of VSMCs in intact tissue. Using immunoblotting, we will quantify the amount of contractile proteins to know whether cardiolipin exacerbates dedifferentiation. We will measure isometric force (tension) of the aorta to determine the functional implications of various cardiolipin concentrations. We will also study the effect of cardiolipin concentrations on VSMCs' mitochondria using in high resolution respirometry.Understanding cardiolipin and its role in mitochondrial regulation of VSMC dedifferentiation will generate the possibility to further control and manipulate the plasticity of the differentiated state under experimental conditions, a fundamental knowledge with potential clinical implications.