Grant: Project Grant

Cardiovascular disease (CVD) is the major cause of death in patients suffering from chronic kidney disease (CKD). Over half of all deaths in patients with end-stage renal disease result from CVD, with mortality rates 10 to 30-fold greater than in the general population. Calcification of the blood vessel wall is a major feature of CKD and is recognized as an important predictor of cardiovascular disease. We have recently discovered that (i) deficiency of T-cell death-associated gene 51 (TDAG51) in mice can protect against CVD, including the formation of calcification in the blood vessel wall, and (ii) mutations in the human gene for TDAG51 correlate with increased risk for CVD. Furthermore, loss of TDAG51 gives rise to an increase in the blood levels of a specific growth factor, termed GDF10, which we have shown to protect against vascular calcification. Based on these novel findings, the purpose of these studies is to investigate how GDF10 is modulated by TDAG51 and whether it can prevent vessel calcification in a mouse model of CKD. By better understanding how GDF10 and TDAG51 modulate vessel calcification, we will have a unique opportunity to develop novel drugs that decrease the accumulation of calcium in the blood vessel, thereby reducing the risk of CVD and its complications.