Supervisors: prof Jaan Eha (TÜ kardioloogia kliinik), prof Mihkel Zilmer (TÜ bio- ja siirdemeditsiini instituut),
vanemteadur Jaak Kals (TÜ bio- ja siirdemeditsiini instituut), vanemteadur Priit Kampus (TÜ kardioloogia kliinik)
Opponent: prof Peter M. Nilsson, MD, PhD, (Lundi Ülikool, Rootsi)
In recent years, increased attention has been paid to vitamin D biofunctions not inherently associated with calcium metabolism. As a result, it has been found that low vitamin D levels, a common clinical problem in Northern Europe, are associated with increased risk of cardiovascular disease. Stiffening of large arteries (including the aorta) is a manifestation of structural and functional changes within the arterial wall that occur with increasing age and cardiovascular disease. Diabetes mellitus significantly increases the risk of arterial damage which highlights the importance of early detection and treatment of diabetic vascular complications. Sustained high blood glucose levels induce irreversible glycation of proteins within tissues including the arterial wall. This impairs the biomechanical properties of the main structural proteins, collagen and elastin, and increases arterial stiffness. Glycation of proteins is exacerbated by persistent high-grade oxidative stress. Diabetes is also associated with excessive activation of the renin-angiotensin system which increases arterial blood pressure and induces arterial remodelling and stiffening in the long term. We found that the early signs of arterial damage in experimental diabetes are increased aortic stiffness and disturbed integrity of elastic fibres within the aortic wall. Diabetes was also characterised by profound accumulation of advanced glycation end-products in the aortic wall, increased oxidative stress level and decreased systemic antioxidant capacity. Administration of vitamin D improved the structural damages within the aortic wall, reduced the glycation of tissue proteins and oxidative stress level, and increased systemic antioxidant capacity. Treatment with an angiotensin II receptor blocker telmisartan similarly improved the structural integrity of the aortic wall and also reduced aortic stiffness.