title: Ethanol increases phosphate-mediated mineralization and osteoblastic transformation of vascular smooth muscle cells.
abstract: Vascular calcification is implicated in the pathogenesis of atherosclerosis, diabetes and chronic kidney disease. Human vascular smooth muscle cells (HSMCs) undergo mineralization in response to elevated levels of inorganic phosphate (Pi) in an active and well-regulated process. This process involves increased activity of alkaline phosphatase and increased expression of core binding factor α-1 (CBF-α1), a bone-specific transcription factor, with the subsequent induction of osteocalcin. It has been shown that heavy alcohol consumption is associated with greater calcification in coronary arteries. The goal of our study was to examine whether ethanol alters mineralization of HSMCs provoked by high Pi. Exposure of HSMCs to ethanol increased extracellular matrix calcification in a dose responsive manner, providing a significant additional calcium deposition at concentrations of ≥60 mmol/l. HSMC calcification was accompanied by further enhancement in alkaline phosphatase activity. Ethanol also provoked a significant increase in the synthesis of osteocalcin. Moreover, in cells challenged with ethanol the expression of CBF-α1, a transcription factor involved in the regulation of osteoblastic transformation of HSMCs, was elevated. The observed effects of ethanol were not due to alterations of phosphate uptake by HSMCs. We conclude that ethanol enhances Pi-mediated human vascular smooth muscle calcification and transition of these cells into osteoblast-like cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Melinda
authors.initials: M
authors.lastname: Oros
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Zavaczki
authors.forename: Csaba
authors.initials: C
authors.lastname: Vadasz
authors.forename: Viktoria
authors.initials: V
authors.lastname: Jeney
authors.forename: Arpad
authors.initials: A
authors.lastname: Tosaki
authors.forename: Istvan
authors.initials: I
authors.lastname: Lekli
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Balla
authors.forename: Laszlo
authors.initials: L
authors.lastname: Nagy
authors.forename: Jozsef
authors.initials: J
authors.lastname: Balla
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D002114:Calcinosis / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010710:Phosphates / Q000032:analysis* / Q000493:pharmacokinetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D010710:Phosphates; C493709:RUNX2 protein, human; D014157:Transcription Factors; D015675:Osteocalcin; D000431:Ethanol; D000469:Alkaline Phosphatase