The mechanism of vascular calcification – a systematic review

Abstract

SummaryCalcification of vessels reduces their elasticity, affecting hemodynamic parameters of the cardiovascular system. The development of arterial hypertension, cardiac hypertrophy, ischemic heart disease or peripheral arterial disease significantly increases mortality in patients over 60 years of age. Stage of advancement and the extent of accumulation of calcium deposits in vessel walls are key risk factors of ischemic events.Vascular calcification is an active and complex process that involves numerous mechanisms responsible for calcium depositions in arterial walls. They lead to increase in arterial stiffness and in pulse wave velocity, which in turn increases cardiovascular disease morbidity and mortality.In-depth study and thorough understanding of vascular calcification mechanisms may be crucial for establishing an effective vasculoprotective therapy.The aim of this study was to present a comprehensive survey of current state-of-the-art research into the impact of metabolic and hormonal disorders on development of vascular calcification.Due to strong resemblance to the processes occurring in bone tissue, drugs used for osteoporosis treatment (calcitriol, estradiol, bisphosphonates) may interfere with the processes occurring in the vessel wall. On the other hand, drugs used to treat cardiovascular problems (statins, angiotensin convertase inhibitors, warfarin, heparins) may have an effect on bone tissue metabolism. Efforts to optimally control calcium and phosphate concentrations are also beneficial for patients with end-stage renal disease, for whom vessel calcification remains a major problem.

Effects of 17β-estradioland raloxifene on endothelial OPG and RANKL secretion

“…Only few studies reported that RANKL is related to cardiovascular events. RANKL secreted by ECs is able to activate RANK receptor and promote an osteogenic differentiation of VSMCs [7]. Cardiovascular events and mortality are significantly higher in these patients with low serum sRANKL levels.…”

“…RANKL induces VC through an increase in bone morphogenetic protein and a decrease in matrix Gla protein, an inhibitor of VC. Estradiol is able to attenuate RANKL-induced VC [7,33]. Therefore, through differential actions in the expression of key proteins, E2 preserves the original contractile VSMCs features, decreasing transdifferentiation towards a calcifying phenotype.…”

“…Estrogen therapy for postmenopausal women reduces vascular calcification [7][8][9]. It has been shown that postmenopausal women with a higher serum estradiol (E2) level had a reduced coronary artery calcium score independent of age and other coronary risk factors.…”

“…This is due to the indirect effect on calcification risk factors as well as direct genomic and extragenomic effect on macrophages, endothelial cells and vascular smooth muscle cells (VSMCs). Estradiol has been found to modulate the secretion of matrix proteins (osteopontin, BSP, MGP, RANKL/OPG), attenuates proliferation and differentiation of VSMCs as well as the activity of calcifying cells [7,11,12].…”

“…Raloxifene therapy involves beneficial impact on cardiovascular risk factors: increases concentration of HDL-cholesterol, and decreases level of LDL-cholesterol, fibrynogen, homocysteine, and lower intensity of inflammatory processes [7,[13][14][15][16][17]. Raloxifene, used in postmenopausal osteoporosis therapy, affects the synthesis and release of intercellular matrix proteins, proliferation and differentiation of VSMCs [12] and has a protective effect on vascular endothelium by, among others, increased expression of eNOS [18][19].…”