title: Medial vascular calcification revisited: review and perspectives.
abstract: Vascular calcifications (VCs) are actively regulated biological processes associated with crystallization of hydroxyapatite in the extracellular matrix and in cells of the media (VCm) or intima (VCi) of the arterial wall. Both patterns of VC often coincide and occur in patients with type II diabetes, chronic kidney disease, and other less frequent disorders; VCs are also typical in senile degeneration. In this article, we review the current state of knowledge about the pathology, molecular biology, and nosology of VCm, expand on potential mechanisms responsible for poor prognosis, and expose some of the directions for future research in this area.
authors.affiliation: Division of Cardiovascular Disease, Department of Internal Medicine, Health Care Center Bitterfeld, Bitterfeld-Wolfen gGmbH, Friedrich-Ludwig-Jahn-Straße 2, D-06749 Bitterfeld-Wolfen, Germany planzer@gzbiwo.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Lanzer
authors.affiliation: Center for Molecular Medicine, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Manfred
authors.initials: M
authors.lastname: Boehm
authors.affiliation: Laboratory of Molecular Toxicology, University of Zaragoza, Zaragoza, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Sorribas
authors.affiliation: National Institute for Research in Computer Science and Control, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Thiriet
authors.affiliation: VascPath, Bern, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Janzen
authors.affiliation: University Heart Center Freiburg, Bad Krozingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zeller
authors.affiliation: Center for Molecular Medicine, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: St Hilaire
authors.affiliation: Cardiovascular Division, King's College London, London, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Shanahan
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D054559:Hyperphosphatemia / Q000503:physiopathology; D008297:Male; D050380:Monckeberg Medial Calcific Sclerosis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D010710:Phosphates / Q000502:physiology; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology; D009626:Terminology as Topic; D017539:Tunica Intima / Q000473:pathology / Q000503:physiopathology; D017540:Tunica Media / Q000473:pathology / Q000503:physiopathology; D061205:Vascular Calcification / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D010710:Phosphates
keywords: Mönckeberg's media sclerosis; Vascular calcifications; Vascular function; Vascular molecular biology and genetics
references.citation: Atherosclerosis. 2012 Oct;224(2):283-90
references.pmid: 22703866
references.citation: Kidney Int. 2011 Feb;79(4):414-22
references.pmid: 20944546
references.citation: Am J Med. 1977 Oct;63(4):615-22
references.pmid: 910809
references.citation: Ann Rheum Dis. 1954 Mar;13(1):15-27
references.pmid: 13149051
references.citation: Semin Dial. 2003 Mar-Apr;16(2):85-94
references.pmid: 12641870
references.citation: Adv Nutr. 2012 Mar 01;3(2):158-65
references.pmid: 22516723
references.citation: Angiology. 2002 Jul-Aug;53(4):483-6
references.pmid: 12143958
references.citation: Calcif Tissue Int. 2013 Oct;93(4):365-73
references.pmid: 23456027
references.citation: Biomark Res. 2013 Apr 01;1(1):17
references.pmid: 24252331
references.citation: Trends Endocrinol Metab. 2014 Feb;25(2):72-9
references.pmid: 24365513
references.citation: Genes Dev. 1998 May 1;12(9):1260-8
references.pmid: 9573043
references.citation: Kidney Int. 2013 Dec;84(6):1145-53
references.pmid: 24107846
references.citation: Nephrol Dial Transplant. 2000 Feb;15(2):218-23
references.pmid: 10648668
references.citation: J Mol Med (Berl). 2013 Dec;91(12):1329-31
references.pmid: 24196572
references.citation: Nephrol Dial Transplant. 2012 May;27(5):1704-7
references.pmid: 22431706
references.citation: Cell Mol Life Sci. 2013 Sep;70(17):3187-97
references.pmid: 23269436
references.citation: Circ Res. 2011 Sep 2;109(6):697-711
references.pmid: 21885837
references.citation: Trends Cardiovasc Med. 2012 May;22(4):93-8
references.pmid: 23040839
references.citation: Nephrol Dial Transplant. 2003 Sep;18(9):1731-40
references.pmid: 12937218
references.citation: Circ Res. 2008 Aug 29;103(5):e28-34
references.pmid: 18669918
references.citation: Circ Res. 2000 Nov 24;87(11):1055-62
references.pmid: 11090552
references.citation: Diabetes Care. 2011 Jan;34(1):156-61
references.pmid: 20929991
references.citation: J Appl Physiol (1985). 2006 Aug;101(2):545-8
references.pmid: 16614356
references.citation: Am J Physiol Heart Circ Physiol. 2009 Nov;297(5):H1673-84
references.pmid: 19749165
references.citation: Arterioscler Thromb Vasc Biol. 2009 May;29(5):761-6
references.pmid: 19213941
references.citation: Front Genet. 2012 Dec 13;3:290
references.pmid: 23248645
references.citation: N Engl J Med. 1993 Oct 21;329(17):1237-9
references.pmid: 8413390
references.citation: Blood. 2004 Nov 15;104(10):3231-2
references.pmid: 15265793
references.citation: AJR Am J Roentgenol. 2003 Sep;181(3):743-8
references.pmid: 12933474
references.citation: Osteoporos Int. 2007 Mar;18(3):251-9
references.pmid: 17151836
references.citation: Am J Kidney Dis. 2010 Dec;56(6):1158-62
references.pmid: 20817370
references.citation: Circ Res. 2011 Aug 19;109(5):578-92
references.pmid: 21852556
references.citation: Circulation. 2013 Jun 18;127(24):2442-51
references.pmid: 23690466
references.citation: Hypertension. 2010 Oct;56(4):555-62
references.pmid: 20733089
references.citation: Circulation. 2013 Jun 18;127(24):2380-2
references.pmid: 23690467
references.citation: Cardiovasc Diabetol. 2013 Jan 09;12:11
references.pmid: 23302066
references.citation: PLoS One. 2013 May 22;8(5):e64558
references.pmid: 23717629
references.citation: Curr Aging Sci. 2011 Jul;4(2):128-36
references.pmid: 21235497
references.citation: Biochem Biophys Res Commun. 2009 Oct 2;387(4):694-9
references.pmid: 19622343
references.citation: J Appl Physiol (1985). 2008 Nov;105(5):1643-51
references.pmid: 18772323
references.citation: Toxicology. 2014 Apr 6;318:40-50
references.pmid: 24561004
references.citation: Diabetes Care. 1994 Nov;17(11):1252-6
references.pmid: 7821163
references.citation: Diabetes Care. 2010 Feb;33(2):408-10
references.pmid: 19910501
references.citation: Bone. 2013 Sep;56(1):42-7
references.pmid: 23702386
references.citation: Int J Cardiol. 2013 Oct 3;168(3):2242-7
references.pmid: 23453445
references.citation: Am J Physiol Cell Physiol. 2011 Jan;300(1):C210-20
references.pmid: 20881235
references.citation: Transplant Proc. 2012 Dec;44(10):2925-31
references.pmid: 23194999
references.citation: Nephrol Dial Transplant. 2014 Jul;29(7):1275-84
references.pmid: 24009287
references.citation: J Clin Invest. 1993 Apr;91(4):1800-9
references.pmid: 8473518
references.citation: Nature. 1997 Mar 6;386(6620):78-81
references.pmid: 9052783
references.citation: J Am Soc Nephrol. 2004 Nov;15(11):2857-67
references.pmid: 15504939
references.citation: J Dtsch Dermatol Ges. 2011 Aug;9(8):586-93
references.pmid: 21435181
references.citation: J Lipid Res. 2012 Aug;53(8):1569-75
references.pmid: 22651923
references.citation: Diabet Med. 2011 Jan;28(1):54-60
references.pmid: 21166846
references.citation: Circ Res. 2013 May 10;112(10):e99-109
references.pmid: 23564641
references.citation: Br J Pharmacol. 2009 Apr;156(8):1267-78
references.pmid: 19302594
references.citation: Annu Rev Physiol. 2012;74:271-97
references.pmid: 22017175
references.citation: Dis Markers. 2013;34(4):229-35
references.pmid: 23396289
references.citation: Circulation. 1999 Nov 23;100(21):2168-76
references.pmid: 10571976
references.citation: Eur Rev Med Pharmacol Sci. 2013 Sep;17(18):2433-40
references.pmid: 24089220
references.citation: Herz. 2001 Jun;26(4):239-44
references.pmid: 11479935
references.citation: Clin Nephrol. 2003 Jun;59(6):463-70
references.pmid: 12834180
references.citation: J Am Coll Cardiol. 2010 Mar 30;55(13):1318-27
references.pmid: 20338492
references.citation: Angiology. 1998 Feb;49(2):137-43
references.pmid: 9482513
references.citation: Z Kardiol. 2001;90 Suppl 3:2-5
references.pmid: 11374027
references.citation: Clin J Am Soc Nephrol. 2009 Dec;4(12):1892-900
references.pmid: 19833908
references.citation: Nat Rev Cardiol. 2010 Sep;7(9):528-36
references.pmid: 20664518
references.citation: Nephrol Dial Transplant. 2009 Jan;24(1):239-46
references.pmid: 18725376
references.citation: Front Genet. 2013 Feb 12;4:4
references.pmid: 23408347
references.citation: Circulation. 2012 Dec 11;126(24):2890-909
references.pmid: 23159553
references.citation: Opt Lett. 2013 May 15;38(10):1715-7
references.pmid: 23938921
references.citation: Calcif Tissue Int. 1994 Apr;54(4):268-73
references.pmid: 8062142
references.citation: J Clin Pathol. 2005 Apr;58(4):447-8
references.pmid: 15790721
references.citation: Hamostaseologie. 2006 Aug;26(3):193-6
references.pmid: 16906234
references.citation: Circ J. 2011;75(11):2705-10
references.pmid: 21799271
references.citation: J Am Soc Nephrol. 2010 Apr;21(4):689-96
references.pmid: 20203159
references.citation: Circ Res. 2013 Jun 21;113(1):72-7
references.pmid: 23616621
references.citation: J Foot Ankle Res. 2010 Dec 22;3:31
references.pmid: 21176166
references.citation: World J Nephrol. 2013 Aug 6;2(3):49-55
references.pmid: 24255887
references.citation: Nephrol Dial Transplant. 2013 May;28(5):1080-4
references.pmid: 23476041
references.citation: Nat Commun. 2012 Jun 06;3:875
references.pmid: 22673902
references.citation: Clin J Am Soc Nephrol. 2008 Jul;3(4):1139-43
references.pmid: 18417747
references.citation: Biochem Biophys Res Commun. 2011 Apr 1;407(1):103-7
references.pmid: 21371424
references.citation: Am J Prev Med. 2011 Mar;40(3):381.e1-10
references.pmid: 21335273
references.citation: N Engl J Med. 2011 Feb 3;364(5):432-42
references.pmid: 21288095
references.citation: Nat Genet. 2012 Feb 12;44(3):254-6
references.pmid: 22327515
references.citation: Vasc Health Risk Manag. 2009;5(1):185-97
references.pmid: 19436645
references.citation: Int J Gen Med. 2013 Aug 09;6:665-9
references.pmid: 23966800
references.citation: Kidney Int. 2013 Jun;83(6):1042-51
references.pmid: 23364520
references.citation: Clin J Am Soc Nephrol. 2008 Sep;3(5):1504-10
references.pmid: 18495950
references.citation: Kidney Int Suppl. 2009 Aug;(113):S1-130
references.pmid: 19644521
references.citation: N Engl J Med. 1987 May 28;316(22):1371-5
references.pmid: 3574413
references.citation: Pediatr Radiol. 1973 Mar;1(1):2-7
references.pmid: 4272099
references.citation: Diab Vasc Dis Res. 2013 Sep;10(5):459-67
references.pmid: 23811603
references.citation: Z Kardiol. 1998 Aug;87(8):586-93
references.pmid: 9782591
references.citation: J Vasc Res. 2012;49(1):77-86
references.pmid: 22105095
references.citation: Kidney Int. 2010 Dec;78(12):1232-9
references.pmid: 20861819
references.citation: Am J Med Genet A. 2013 Feb;161A(2):360-70
references.pmid: 23322711
references.citation: Hypertension. 2010 Mar;55(3):579-92
references.pmid: 20101002
references.citation: J Clin Invest. 2003 Aug;112(3):357-66
references.pmid: 12897203
references.citation: Trends Cardiovasc Med. 2013 Apr;23(3):71-9
references.pmid: 23290463
references.citation: Arch Biochem Biophys. 1984 May 15;231(1):1-8
references.pmid: 6326671
references.citation: Calcif Tissue Int. 2009 Dec;85(6):523-9
references.pmid: 19806384
references.citation: Arterioscler Thromb Vasc Biol. 1996 Aug;16(8):978-83
references.pmid: 8696962
references.citation: Kidney Int. 2014 Jan;85(1):142-50
references.pmid: 23884339
references.citation: Circ Res. 2013 Jan 4;112(1):17-22
references.pmid: 23093573
references.citation: Pediatr Radiol. 1990;20(7):520-3
references.pmid: 2216585
references.citation: Br J Ophthalmol. 1999 Sep;83(9):1091-2
references.pmid: 10636687
references.citation: Acta Radiol Suppl. 1950;80:1-80
references.pmid: 14868550
references.citation: Nat Genet. 2003 Aug;34(4):379-81
references.pmid: 12881724
references.citation: Circulation. 2007 Dec 11;116(24):2782-5
references.pmid: 18071088
references.citation: Contrib Nephrol. 2013;180:74-85
references.pmid: 23652551
references.citation: Biomed Mater Eng. 2006;16(4 Suppl):S155-61
references.pmid: 16823107
references.citation: Am J Physiol Heart Circ Physiol. 2012 Sep 1;303(5):H619-28
references.pmid: 22777419
references.citation: J Am Soc Nephrol. 2010 Jan;21(1):103-12
references.pmid: 19959717
references.citation: Circ Res. 2008 Jun 20;102(12):1529-38
references.pmid: 18497329
references.citation: Arterioscler Thromb. 1994 May;14(5):840-56
references.pmid: 8172861
references.citation: Z Kardiol. 2001;90 Suppl 3:6-11
references.pmid: 11374035
references.citation: Z Kardiol. 2000;89 Suppl 2:28-35
references.pmid: 10769401
references.citation: Circulation. 1995 Sep 1;92(5):1355-74
references.pmid: 7648691
references.citation: Circulation. 2009 Apr 7;119(13):1785-94
references.pmid: 19307473
references.citation: J Am Coll Cardiol. 2013 Jul 23;62(4):263-71
references.pmid: 23684677
references.citation: J Am Heart Assoc. 2013 Apr 08;2(2):e002154
references.pmid: 23568343
references.citation: Eur Heart J. 2006 Nov;27(21):2588-605
references.pmid: 17000623
references.citation: J Am Col Certif Wound Spec. 2011 Mar 27;2(4):66-72
references.pmid: 24527153
references.citation: Mol Genet Metab. 2011 May;103(1):44-50
references.pmid: 21371928
references.citation: Hypertension. 2010 Oct;56(4):563-70
references.pmid: 20733088
references.citation: Circulation. 2007 Dec 11;116(24):2841-50
references.pmid: 18040026
references.citation: J Endocrinol Invest. 2008 Oct;31(10):925-31
references.pmid: 19092300