IP: Dr. Muñoz Torres Manuel

Resumen del proyecto: Patients with type 2 diabetes mellitus have an increased risk of developing cardiovascular diseases and bone metabolic disease, with common molecular mechanisms between both diseases. Specifically, the Wnt signaling pathway, involved in the regulation of bone metabolism, has recently shown evidence of its involvement in vascular pathologies. Of particular relevance is one of the antagonists of the Wnt pathway, sclerostin, which acts by inhibiting osteoblastogenesis. The production of sclerostin was described only in osteocytes. For this reason sclerostin has been chosen as a therapeutic target, through the use of anti-sclerostin antibodies against osteoporosis. However, in vitro studies have shown that the calcified vascular smooth muscle cells suffer a phenotype transition and produce sclerostin. In models of type 2 diabetes mellitus, it has been shown that sclerostin is overexpressed in calcified cardiovascular tissues. In this context, our objective is to identify new protein biomarkers that are predictive of the progression and severity of atherosclerotic disease and vascular calcification, comparing them with biomarkers of bone mineralization. The biomarkers found will be validated by cross-sectional studies in serum of patients with T2DM with and without atherosclerotic disease. In addition, it is proposed to evaluate sclerostin as a marker of genetic and protein susceptibility of atherosclerotic disease through cross-sectional studies, as well as to carry out an approximation to the validity of anti- sclerostin antibody therapy in vascular tissue calcification processes.

Entidad financiadora: Consejería de Salud de la Junta de Andalucía