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Atherosclerosis is characterized by an invasion of inflammatory cells, accumulation of lipids and the formation of fatty streaks (plaques) which subsequently allow accumulation of calcium and other minerals leading to a disturbance in the vascular endothelium and its regulatory role in arterial function. Vascular calcification is a different process, stringently regulated mainly by local factors, in which osteoblast\u2010like cells accumulate in the muscular layer of arteries ultimately taking on the physiological appearance of bone. The elevated stiffness of the arteries leads to severe vascular complications in brain, heart and kidneys. Recently, evidence from animal experiments as well as clinical and epidemiological results suggests that long\u2010term treatment with warfarin, but not with the novel direct anticoagulants, can increase the risk or even induce vascular calcification in some individuals. Gamma\u2010carboxylation is an enzymatic process not only needed for activation of vitamin K but also other proteins which participate in bone formation and vascular calcification. Thus, reduced expression of the vitamin K\u2010dependent proteins which physiologically inhibit calcification of cellular matrix could be postulated to lead to vascular calcification. Published clinical data, describing at present a few thousand patients, need to be supplemented with controlled studies to confirm this interesting hypothesis.<\/jats:p>","DOI":"10.1111\/bcpt.12834","type":"journal-article","created":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T00:34:38Z","timestamp":1498091678000},"page":"19-24","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Vascular Calcification, Vitamin K and Warfarin Therapy \u2013 Possible or Plausible Connection?"],"prefix":"10.1111","volume":"122","author":[{"given":"Aino","family":"Siltari","sequence":"first","affiliation":[{"name":"Faculty of Medicine Pharmacology University of Helsinki Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heikki","family":"Vapaatalo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Pharmacology University of Helsinki Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,7,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.21037\/cdt.2016.06.01"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/07853899109150522"},{"issue":"1","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2165\/00003495-199200441-00005","article-title":"Calcium overload \u2013 an important mechanism in hypertension and arteriosclerosis","volume":"44","author":"Fleckenstein\u2010Gr\u00fcn G","year":"1992","journal-title":"Drugs"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr063"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.154260"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.743161"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/nrendo.2012.36","article-title":"Arterial calcification and bone physiology: role of the bone \u2013 vascular axis","volume":"8","author":"Thomson B","year":"2012","journal-title":"Nat Rev Endocrinol"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2012.00095"},{"key":"e_1_2_10_10_1","first-page":"1773","volume-title":"Goodman & Gilman \u0301s The Pharmacological Basis of Therapeutics","author":"Marcus R","year":"2001"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3402\/fnr.v56i0.5505"},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1160\/TH08-03-0147","article-title":"Metabolism and cell biology of vitamin K","volume":"100","author":"Schearer MJ","year":"2008","journal-title":"Thromb Haemost"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.5001\/omj.2014.44"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/386078a0"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2015.05.046"},{"key":"e_1_2_10_16_1","first-page":"849","volume-title":"Goodman & Gilma's The Pharmacological Basis of Therapeutics","author":"Weitz JI","year":"2011"},{"key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.2215\/CJN.00770208","article-title":"Vitamin K\u2010dependent proteins, warfarin, and vascular calcification","volume":"3","author":"Danzinger J","year":"2008","journal-title":"Clin J Am Soc Nephrol"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/clc.20865"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2012.03.002"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.300260"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.4236\/pp.2014.512119","article-title":"Effects of Vitamin K\u20101 and menaquinone\u20107 on vascular function and blood pressure in warfarin\u2010induced calcification\u2010model in rats","volume":"5","author":"Siltari A","year":"2014","journal-title":"Pharmacol Pharm"},{"key":"e_1_2_10_22_1","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.4236\/pp.2014.513129","article-title":"Possible correlation between INR and serum calcium","volume":"5","author":"Helin TA","year":"2014","journal-title":"Pharmacol Pharm"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.304392"},{"key":"e_1_2_10_24_1","doi-asserted-by":"crossref","first-page":"e002665","DOI":"10.1161\/JAHA.115.002665","article-title":"Increased peripheral calcification in patients receiving warfarin","volume":"5","author":"Han KH","year":"2016","journal-title":"J Am Heart Assoc"},{"key":"e_1_2_10_25_1","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1007\/s00223-009-9300-4","article-title":"Does prolonged warfarin exposure potentiate coronary calcification in humans? 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