PMID- 22260235 OWN - NLM STAT- MEDLINE DCOM- 20130107 LR - 20211021 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 16 IP - 9 DP - 2012 Sep TI - Ethanol increases phosphate-mediated mineralization and osteoblastic transformation of vascular smooth muscle cells. PG - 2219-26 LID - 10.1111/j.1582-4934.2012.01533.x [doi] AB - 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 alpha-1 (CBF-alpha1), 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-alpha1, 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. CI - (c) 2012 The Authors Journal of Cellular and Molecular Medicine (c) 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. FAU - Oros, Melinda AU - Oros M AD - Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. FAU - Zavaczki, Erzsebet AU - Zavaczki E FAU - Vadasz, Csaba AU - Vadasz C FAU - Jeney, Viktoria AU - Jeney V FAU - Tosaki, Arpad AU - Tosaki A FAU - Lekli, Istvan AU - Lekli I FAU - Balla, Gyorgy AU - Balla G FAU - Nagy, Laszlo AU - Nagy L FAU - Balla, Jozsef AU - Balla J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (Core Binding Factor Alpha 1 Subunit) RN - 0 (Phosphates) RN - 0 (RUNX2 protein, human) RN - 0 (Transcription Factors) RN - 104982-03-8 (Osteocalcin) RN - 3K9958V90M (Ethanol) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Alkaline Phosphatase/metabolism MH - Calcinosis/*pathology MH - Cell Survival/drug effects MH - Cells, Cultured MH - Core Binding Factor Alpha 1 Subunit/genetics/metabolism MH - Ethanol/*adverse effects MH - Extracellular Matrix/metabolism MH - Gene Expression Regulation MH - Humans MH - Muscle, Smooth, Vascular/*cytology/drug effects/pathology MH - Myocytes, Smooth Muscle/cytology/*drug effects/metabolism MH - Osteoblasts/*cytology/drug effects/metabolism MH - Osteocalcin/genetics/metabolism MH - Phosphates/*analysis/pharmacokinetics MH - Transcription Factors/genetics/metabolism PMC - PMC3822991 EDAT- 2012/01/21 06:00 MHDA- 2013/01/08 06:00 PMCR- 2012/09/01 CRDT- 2012/01/21 06:00 PHST- 2012/01/21 06:00 [entrez] PHST- 2012/01/21 06:00 [pubmed] PHST- 2013/01/08 06:00 [medline] PHST- 2012/09/01 00:00 [pmc-release] AID - 10.1111/j.1582-4934.2012.01533.x [doi] PST - ppublish SO - J Cell Mol Med. 2012 Sep;16(9):2219-26. doi: 10.1111/j.1582-4934.2012.01533.x.