Abstract
BackgroundSince aortic calcification has been shown to initiate in the lower zone of well-thickened plaques (LZP) adjacent to the aortic media of rabbits fed supplemental cholesterol diets, a restricted supply of serum to vascular cells could play a role in vascular calcification. This study was designed to use a cell culture model to support this hypothesis.ResultsRabbit aortic smooth muscle cells were grown to confluence in a culture media containing 10 % fetal bovine serum (FBS). The confluent cells were then exposed to the media for 2 hrs with or without serum at a Ca × P ion product range of 4.5–9.4 mM2. In contrast to the cells cultured in the presence of FBS, confluent cells in its absence displayed marked mineral-positive alizarin red staining and infrared absorption of mineral phosphate. A kinetic parameter C1/2 was used to designate the concentration of serum or its protein constituents needed to reduce the deposition of Ca and P by half. The C1/2 for FBS and rabbit serum was 0.04–0.07 % The C1/2 value for rabbit serum proteins was 13.5 μg/ml corresponding to the protein concentration in 0.06 % of serum. This C1/2 was markedly smaller than 86.2 μg/ml for bovine serum albumin present in 0.37 % serum (p < 0.05). Serum depletion also caused marked membrane translocation as evidenced through a specific apoptosis dye uptake by cells. The proteomic analysis of calcifying vesicles, which can be released by serum depletion, revealed several calcification-related proteins.ConclusionThe aortic smooth muscle cell culture model suggests that serum depletion may play a role in the initiation of aortic calcification. The serum exhibits remarkable ability to inhibit cell-mediated calcification.
Highlights
Since aortic calcification has been shown to initiate in the lower zone of wellthickened plaques (LZP) adjacent to the aortic media of rabbits fed supplemental cholesterol diets, a restricted supply of serum to vascular cells could play a role in vascular calcification
In spite of the evidence that both physiological and pathological calcification is regulated through gene expressions of osteopontin (OPN) [4], matrix γ-carboxyglutamate protein (MGP) [5], and osteoprotegerin (OPG) [6], the mechanisms whereby calcium phosphate minerals are initially deposited in the arterial wall remain uncertain [7,8,9]
Induction of calcification in vitro by serum depletion To test the hypothesis that serum restriction in the lower zone of plaques initiates focal calcification [7,18,19], we used a cell culture model to determine whether calcification in rabbit aortic smooth muscle cell culture could be induced by the deletion of serum from the culture media
Summary
Since aortic calcification has been shown to initiate in the lower zone of wellthickened plaques (LZP) adjacent to the aortic media of rabbits fed supplemental cholesterol diets, a restricted supply of serum to vascular cells could play a role in vascular calcification. An alternative hypothesis for the participation of a remote bone resorption process in vascular calcification was advocated by Price and colleagues using hypervitamin Dtreated rat model [14]. This model was deduced from the observation that subcutaneous injections of specific bone resorption inhibitors such as bisphosphonates to the rat inhibited calcification in arterial media. Another interesting observation that may underlie the cause of vascular calcification in human subjects was the finding of mineral-associated nanobacteria-like structures in advanced atherosclerotic aortic walls [15]
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