Beneficial effects of vitamin D and angiotensin II receptor blocker on arterial damage
Date
2013-08-30
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Abstract
Vitamiin D biofunktsioonidest on viimastel aastatel palju tähelepanu pööratud toimetele, mis pole otseselt seotud kaltsiumi ainevahetusega. Nii on leitud, et madal vitamiin D tase, mis on levinud kliiniline probleem Põhja-Euroopas, on seotud kõrgema südame- ja veresoonkonna haiguste riskiga. Suurte arterite (sh. aordi) seinte jäigenemine on organismi vananemise ja südame- ja veresoonkonna haigustega kaasnev protsess, mille aluseks on arterite struktuursed-funktsionaalsed muutused. Diabeedi korral on oluliselt tõusnud risk arterite kahjustuste tekkeks, mille varane tuvastamine ja leevendamine on diabeedi konventsionaalses ravis määrava tähtsusega. Püsivalt kõrge veresuhkru tase soodustab kudedes, sealhulgas arterite seintes, valkude pöördumatut glükeerimist. See halvendab põhiliste struktuursete valkude, kollageeni ja elastiini, biomehaanilisi omadusi ja tõstab arterite jäikust. Valkude glükeerimist süvendab tugev kestev oksüdatiivne stress. Diabeediga kaasneb ka liigne reniin-angiotensiin süsteemi aktivatsioon, mis tõstab arteriaalset vererõhku ning pikas perspektiivis süvendab arterite remodelleerumist ja jäigenemist. Me leidsime, et eksperimentaalses diabeedimudelis oli arterikahjustuste varajasteks tunnusteks suurenenud aordi jäikus ning halvenenud elastsete kiudude struktuurne terviklikkus. Aordiseinas olid kuhjunud glükeerimise lõpp-produktid, millega kaasnes oluline oksüdatiivse stressi taseme tõus ning süsteemse antioksüdantse vastuse nõrgenemine. Vitamiin D lisamanustamisel paranesid aordiseina struktuursed kahjustused, vähenes koevalkude glükeerimine ja oksüdatiivse stressi tase ning paranes antioksüdantne vastus. Samal määral vähendas diabeedimudelis aordiseina struktuurseid muutuseid angiotensiin II retseptori blokaatori telmisartaani manustamine, mis lisaks langetas aordi jäikust.
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.
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.
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Keywords
diabeet, arterioskleroos, D-vitamiin, angiotensiini antagonistid, oksüdatiivne stress, diabetes, arteriosklerosis, vitamin D, angiotensin receptor blockers, oxidative stress