Direct comparison of regulators of calcification between bone and vessels in humans.
Calcification is not only physiologically present in bone but is a main pathophysiological process in vasculature, favouring cardiovascular diseases. Our aim was to investigate changes in the expression of calcification regulators during vascular calcification in bone and vasculature. Levels of gene expression of osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), osteopontin (OPN), matrix gla protein (MGP), bone sialoprotein (BSP), SMAD6, and runt-related transcription factor 2 (RUNX2) were determined in bone, aorta, and external iliac artery tissue samples of transplant donors. Histological stages of atherosclerosis (AS) in vessels are defined as "no changes", "intima thickening", or "intima calcification". Patients' bone samples were subgrouped accordingly. We demonstrate that in vessels BSP and OPN expression significantly increased during intima thickening and decreased during intima calcification, whereas the expression of regulators of calcification did not significantly change in bone during intima thickening and intima calcification. At the stage of intima thickening, MGP, OPG, and SMAD6 expression and at stage of intima calcification only MGP expression was lower in bone than in vessel. The expression of BSP and RANKL was regulated in opposite ways in bone and vessels, whereas the expression of MGP, OC, RUNX2, and OPN was regulated in a tissue-specific manner. Our study is the first direct comparison of gene expression changes during AS progression in bone and vessels. Our results indicate that changes in the expression of regulators of calcification in the vessel wall as well as in bone occur early in the calcification process, even prior to deposition of calcium/phosphate precipitation.
Department of Internal Medicine, Divison of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
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Schweighofer
Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria.
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Aigelsreiter
Department of Internal Medicine, Divison of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
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Trummer
Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria.
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Graf-Rechberger
Department of Internal Medicine, Divison of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
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Hacker
Department of Surgery, Division of Transplantation Surgery, Medical University of Graz, Auenbruggerplatz 29, 8036 Graz, Austria.
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Kniepeiss
Department of Surgery, Division of Transplantation Surgery, Medical University of Graz, Auenbruggerplatz 29, 8036 Graz, Austria.
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Wagner
Department of Surgery, Division of Transplantation Surgery, Medical University of Graz, Auenbruggerplatz 29, 8036 Graz, Austria.
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Stiegler
Department of Internal Medicine, Divison of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
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Trummer
Department of Internal Medicine, Divison of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria; Joanneum Research Health, Elisabethstrasse 5, 8010 Graz, Austria.
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Pieber
Department of Internal Medicine, Divison of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. Electronic address: barbara.obermayer@medunigraz.at.
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Obermayer-Pietsch
Department of Surgery, Division of Transplantation Surgery, Medical University of Graz, Auenbruggerplatz 29, 8036 Graz, Austria.
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Müller
D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D002114:Calcinosis / Q000235:genetics / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007083:Iliac Artery / Q000473:pathology; D008297:Male; D008875:Middle Aged
Atherosclerosis; Gene expression; Regulators of calcification; Vascular calcification