Grant: Operating Grant

Lay Summary: Abnormal mineral deposition in the soft tissues (calcification) can be seen in some life-threatening diseases. Mineral accumulation in the blood vessels is a common example of soft tissue calcification. Vascular calcification can be seen in diseases, such as atherosclerosis, chronic kidney diseases and type II diabetes. Soft tissue calcification can further complicate the prognosis and management of these diseases, which may in turn lead to increased morbidity. Although vascular calcification is prevalent in aging population and considered as a risk factor for many vascular diseases, the underlying mechanisms that regulate vascular calcification is poorly understood. A better understanding of the determinants of this complex process will identify novel therapeutic targets to prevent and manage vascular calcification in humans. The long-term objective of our study is to understand the process of vascular calcification and to identify its genetic determinants. Our objective for this project is to analyze the vascular calcification trait in a mouse model that lacks a potent anti-mineralization protein in the vascular tissues. In this model, absence of the anti-mineralization protein leads to massive deposition of minerals in the arterial walls. We plan to investigate the cell behaviour in the calcified arteries of this model and also investigate how alterations of protein synthesis and breakdown in the vascular walls may affect the calcification process. Finally, we will treat this model with a pharmacologic agent to inhibit protein breakdown with a goal to prevent vascular calcification.