The role of Bone Morphogenetic Protein 7 in the pathophysiology and treatment of vascular calcification associated with chronic renal failure

Vascular calcification (VC) is an important complication of chronic renal failure (CRF), and a risk factor for reduced survival. Osteoblast-like cells in the vessel wall derived from resident vascular smooth muscle cells (VSMC) are considered central to the pathogenesis of VC, which is exacerbated by mineral ion abnormalities inherent in renal osteodystrophy (ROD). Nevertheless, its aetiology is incompletely understood, and no effective therapies exist. Recendy, CRF has been characterised as a state of Bone Morphogenetic Protein 7 (BMP7) deficiency, and animal studies have shown that administration of this renal morphogen is efficacious in treating several aspects of renal failure, including progressive renal fibrosis and ROD. The hypothesis of this thesis is that BMP7 deficiency contributes to the pathogenesis of VC, by facilitating the emergence of the osteoblast-like cell, and that exogenous BMP7 administration abrogates it by normalising VSMC behaviour. This hypothesis was tested in atherosclerotic Low Density Lipoprotein Receptor Null (ldlf/) mice. Uraemia was superimposed surgically to generate VC. Animals received