Role of vitamin K-dependent proteins in the arterial vessel wall

M. L. L. Chatrou; C. P. Reutelingsperger; L. J. Schurgers

doi:10.5482/ha-1157

Hämostaseologie, Table of Contents

Hamostaseologie 2011; 31(04): 251-257
DOI: 10.5482/ha-1157

Review

Schattauer GmbH

Role of vitamin K-dependent proteins in the arterial vessel wall

Die Rolle Vitamin-K-abhängiger Proteine in der arteriellen Gefäßwand

Authors

M. L. L. Chatrou

¹Department of Biochemistry, CARIM, Maastricht University, the Netherlands
C. P. Reutelingsperger

¹Department of Biochemistry, CARIM, Maastricht University, the Netherlands
L. J. Schurgers

¹Department of Biochemistry, CARIM, Maastricht University, the Netherlands

Abstract

Summary

Vitamin K was discovered early last century at the same time as the vitamin K-antagonists. For many years the role of vitamin K was solely ascribed to coagulation and coagulation was thought to be involved only at the venous blood side. This view has dramatically changed with the discovery of vitamin K-dependent proteins outside the coagulation cascade and the role of coagulation factors at the arterial side. Vitamin K-dependent proteins are involved in the regulation of vascular smooth muscle cell migration, apoptosis, and calcification. Vascular calcification has become an important independent predictor of cardiovascular disease. Vitamin K-antagonists induce inactivity of inhibitors of vascular calcification, leading to accelerated calcification. The involvement of vitamin K-dependent proteins such as MGP in vascular calcification make that calcification is amendable for intervention with high intake of vitamin K. This review focuses on the effect of vitamin K-dependent proteins in vascular disease.

Zusammenfassung

Vitamin K wurde im frühen vergangenen Jahrhundert zur gleichen Zeit wie die Vitamin K-Antagonisten entdeckt. Über Jahre wurde die Rolle von Vitamin K ausschließlich der Blutgerinnung zugeschrieben und man glaubte, dass sich die Koagulation nur auf der venösen Blutseite abspiele. Mit der Entdeckung Vitamin-K-abhängiger Proteine außerhalb der Gerinnungskaskade und der Bedeutung von Gerinnungsfaktoren auf der arteriellen Seite hat sich diese Sicht grundlegend geändert. Vitamin-K-abhängige Proteine sind an der Regulation der Migration glatter Gefäßmuskelzellen sowie an der Apoptose und Kalzifikation beteiligt. Vaskuläre Kalzifikation ist ein wichtiger unabhängiger Prognosefaktor für kardiovaskuläre Erkrankungen. Vitamin-KAntagonisten induzieren eine Inaktivität von Inhibitoren der vaskulären Kalzifikation und führen so zu beschleunigter Verkalkung. Die Beteiligung Vitamin-K-abhängiger Proteine wie MGP an der vaskulären Kalzifikation eröffnet eine Möglichkeit zur therapeutischen Intervention durch die Einnahme hoher Dosen Vitamin K. Das Thema dieses Reviews ist die Wirkung Vitamin-K-abhängiger Proteine auf vaskuläre Erkrankungen.

Keywords

Vitamin K - vitamin K-antagonists - MGP - vascular calcification

Schlüsselwörter

Vitamin K - Vitamin-K-Antagonisten - MGP - vaskuläre Kalzifikation

Full Text

References

References
1 Shearer MJ, Gorska R, Harrington DJ. et al. Vitamin K. Vitamins and Vitamin-Like Nutrients for Prevention of Human Diseases. Berlin: DeGruyter; 2011: 515-559.
2 Stenflo J, Ferlund P, Egan W, Roepstorff P. Vitamin K dependent modifications of glutamic acid residues in prothrombin. Proc Natl Acad Sci USA 1974; 71: 2730-2733.
3 Nelsestuen G, Zytkovicz T, Howard J. The mode of action of vitamin K. Identification of gamma-carboxyglutamic acid as a component of prothrombin. J Biol Chem 1974; 249: 6347-6350.
4 Wu S, Cheung W, Frazier D, Stafford D. Cloning and expression of the cDNA for human gamma-glutamyl carboxylase. Science 1991; 254: 1634-1636.
5 Li T, Chang C, Jin D. et al. Identification of the gene for vitamin K epoxide reductase. Nature 2004; 427: 541-544.
6 Rost S, Fregin A, Ivaskevicius V. et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 2004; 427: 537-541.
7 Westhofen P, Watzka M, Marinova M. et al. Human vitamin K 2,3-epoxide reductase complex subunit 1-like 1 (VKORC1L1) mediates vitamin K-dependent intracellular antioxidant function. J Biol Chem 2011; 286: 15085-15094.
8 Conly J, Stein K. Quantitative and qualitative measurements of K vitamins in human intestinal contents. Am J Gastroenterol 1992; 87: 311-316.
9 Booth S, Martini L, Peterson J. et al. Dietary phylloquinone depletion and repletion in older women. J Nutr 2003; 133: 2565-2569.
10 Food and Nutrition Board. Institute of Medicine. In: Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vnandium, and zinc. Washington, DC: 2001
11 Gijsbers B, Jie K, Vermeer C. Effect of food composition on vitamin K absorption in human volunteers. Br J Nutr 1996; 76: 223-229.
12 Schurgers LJ, Vermeer C. Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis 2000; 30: 298-307.
13 Schurgers LJ, Teunissen KJF, Hamulyák K. et al. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 2007; 109: 3279-3283.
14 Schurgers LJ, Vermeer C. Differential lipoprotein transport pathways of K-vitamins in healthy subjects. Biochim Biophys Acta 2002; 1570: 27-32.
15 Link K. The discovery of dicumarol and its sequels. Circulation 1959; 19: 97-107.
16 Campbell MA. Haemorrhagic disease in cattle. J Biol Chem 1941; 18: 21-33.
17 Shapiro SS. Treating thrombosis in the 21st century. N Engl J Med 2003; 349: 1762-1764.
18 Stafford D. The vitamin K cycle. J Thromb Haemost 2005; 03: 1873-1878.
19 Fasco M, Principe L. Vitamin K1 hydroquinone formation catalyzed by DT-diaphorase. Biochem Biophys Res Commun 1982; 104: 187-192.
20 Wallin R, Gebhardt O, Prydz H. NAD(P)H dehydrogenase and its role in the vitamin K (2-methyl3-phytyl-1,4-naphthaquinone)-dependent carboxylation reaction. Biochem J 1978; 169: 95-101.
21 Price P, Kaneda Y. Vitamin K counteracts the effect of warfarin in liver but not in bone. Thromb Res 1987; 46: 121-131.
22 Wallin R, Cain D, Sane D. Matrix Gla protein synthesis and gamma-carboxylation in the aortic vessel wall and proliferating vascular smooth muscle cells--a cell system which resembles the system in bone cells. Thromb Haemost 1999; 82: 1764-1767.
23 Burstyn-Cohen T, Heeb M, Lemke G. Lack of protein S in mice causes embryonic lethal coagulopathy and vascular dysgenesis. J Clin Invest 2009; 119: 2942-2953.
24 Borissoff JI, Heeneman S, Kilinç E. et al. Early atherosclerosis exhibits an enhanced procoagulant state. Circulation 2010; 122: 821-830.
25 Borissoff JI, Spronk HM, Ten Cate H. The hemostatic system as a modulator of atherosclerosis. N Engl J Med 2011; 364: 1746-1760.
26 Bea F, Kreuzer J, Preusch M. et al. Melagatran reduces advanced atherosclerotic lesion size and may promote plaque stability in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2006; 26: 2787-2792.
27 Anderson H, Maylock C, Williams J. et al. Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells. Nat Immunol 2003; 04: 87-91.
28 Tabas I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol 2010; 10: 36-46.
29 Liao D, Wang X, Li M. et al. Human protein S inhibits the uptake of AcLDL and expression of SR-A through Mer receptor tyrosine kinase in human macrophages. Blood 2009; 113: 165-174.
30 Hurtado B, Munoz X, Recarte-Pelz P. et al. Expression of the vitamin K-dependent proteins GAS6 and protein S and the TAM receptor tyrosine kinases in human atherosclerotic carotid plaques. Thromb Haemost 2011; 105: 873-882.
31 Saller F, Brisset AC, Tchaikovski SN. et al. Generation and phenotypic analysis of protein S-deficient mice. Blood 2009; 114: 2307-2314.
32 Levi M, Dörffler-Melly J, Reitsma P. et al. Aggravation of endotoxin-induced disseminated intravascular coagulation and cytokine activation in heterozygous protein-C-deficient mice. Blood 2003; 101: 4823-4827.
33 Okajima K. Regulation of inflammatory responses by natural anticoagulants. Immunol Rev 2001; 184: 258-274.
34 Manfioletti G, Brancolini C, Avanzi G, Schneider C. The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade. Mol Cell Biol 1993; 13: 4976-4985.
35 Son B, Kozaki K, Iijima K. et al. Statins protect human aortic smooth muscle cells from inorganic phosphate-induced calcification by restoring Gas6-Axl survival pathway. Circ Res 2006; 98: 1024-1031.
36 Proudfoot D, Skepper JN, Hegyi L. et al. Apoptosis regulates human vascular calcification in vitro: evidence for initiation of vascular calcification by apoptotic bodies. Circ Res 2000; 87: 1055-1062.
37 Ueland T, Gullestad L, Dahl CP. et al. Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis. J Intern Med 2010; 268: 483-492.
38 Schurgers LJ, Barreto DV, Barreto FC. et al. The circulating inactive form of matrix Gla protein is a surrogate marker for vascular calcification in chronic kidney disease: A preliminary report. Clin J Am Soc Nephrol 2010; 05: 568-575.
39 Luo G, Ducy P, McKee M. et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 1997; 385: 78-81.
40 Murshed M, Schinke T, McKee M, Karsenty G. Extracellular matrix mineralization is regulated locally; different roles of two gla-containing proteins. J Cell Biol 2004; 165: 625-630.
41 Price P, Faus S, Williamson M. Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler Thromb Vasc Biol 1998; 18: 1400-1407.
42 Schurgers LJ, Aebert H, Vermeer C. et al. Oral anticoagulant treatment: friend or foe in cardiovascular disease?. Blood 2004; 104: 3231-3232.
43 Koos R, Mahnken A, Muhlenbruch G. et al. Relation of oral anticoagulation to cardiac valvular and coronary calcium assessed by multislice spiral computed tomography. Am J Cardiol 2005; 96: 747-749.
44 Rennenberg RJMW, van Varik BJ, Schurgers LJ. et al. Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans. Blood 2010; 115: 5121-5123.
45 Rosenhek R, Binder T, Porenta G. et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med 2000; 343: 611-617.
46 Zieman S, Melenovsky V, Kass D. Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol 2005; 25: 932-943.
47 Doherty TM, Asota K, Fitzpatrick LA. et al. Calcification in atherosclerosis: Bone biology and chronic inflammation at the arterial crossroads. Proc Natl. Acad Sci 2003; 100: 11201-11206.
48 Raggi P, Shaw L, Berman D, Callister T. Prognostic value of coronary artery calcium screening in subjects with and without diabetes. J Am Coll Cardiol 2004; 43: 1663-1669.
49 Rennenberg RJMW, Kessels AGH, Schurgers LJ. et al. Vascular calcifications as a marker of increased cardiovascular risk: a meta-analysis. Vasc Health Risk Manag 2009; 05: 185-197.
50 Budoff M, Shaw L, Liu S. et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol 2007; 49: 1860-1870.
51 Raggi P, Callister T, Shaw L. Progression of coronary artery calcium and risk of first myocardial infarction in patients receiving cholesterol-lowering therapy. Arterioscler Thromb Vasc Biol 2004; 24: 1272-1277.
52 Alexopoulos N, Raggi P. Calcification in atherosclerosis. Nat Rev Cardiol 2009; 06: 681-688.
53 Demer L, Tintut Y. Vascular calcification: pathobiology of a multifaceted disease. Circulation 2008; 117: 2938-2948.
54 Naghavi M, Libby P, Falk E. et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II. Circulation 2003; 108: 1772-1778.
55 Vengrenyuk Y, Carlier S, Xanthos S. et al. A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps. Proc Natl Acad Sci USA 2006; 103: 14678-14683.
56 Dhore C, Cleutjens J, Lutgens E. et al. Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol 2001; 21: 1998-2003.
57 Shanahan CM, Cary NR, Metcalfe JC, Weissberg PL. High expression of genes for calcification-regulating proteins in human atherosclerotic plaques. J Clin Invest 1994; 93: 2393-2402.
58 Nadra I, Mason J, Philippidis P. et al. Proinflammatory activation of macrophages by basic calcium phosphate crystals via protein kinase C and MAP kinase pathways: A vicious cycle of inflammation and arterial calcification?. Circ Res 2005; 96: 1248-1256.
59 Narayan S, Pazar B, Ea H-K. et al. Octacalcium phosphate crystals induce inflammation in vivo through interleukin-1 but independent of the NLRP3 inflammasome in mice. Arthritis Rheum 2011; 63: 422-433.
60 Pazár B, Ea H-K, Narayan S. et al. Basic calcium phosphate crystals induce monocyte/macrophage IL-1β secretion through the NLRP3 inflammasome in vitro. J Immunol 2011; 186: 2495-2502.
61 Ewence A, Bootman M, Roderick H. et al. Calcium phosphate crystals induce cell death in human vascular smooth muscle cells. A potential mechanism in atherosclerotic plaque destabilization. Circ Res 2008; 103: e28-e34.
62 Nasir K, Rivera J, Yoon Y. et al. Variation in atherosclerotic plaque composition according to increasing coronary artery calcium scores on computed tomography angiography. Int J Cardiovasc Imaging 2010; 26: 923-932.
63 Motoyama S, Kondo T, Sarai M. et al. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J Am Coll Cardiol 2007; 50: 319-326.
64 Keelan PC, Bielak LF, Ashai K. et al. Long-term prognostic value of coronary calcification detected by electron-beam computed tomography in patients undergoing coronary angiography. Circulation 2001; 104: 412-417.
65 Huang H, Virmani R, Younis H. et al. The impact of calcification on the biomechanical stability of atherosclerotic plaques. Circulation 2001; 103: 1051-1056.
66 Ehara S, Kobayashi Y, Yoshiyama M. et al. Spotty calcification typifies the culprit plaque in patients with acute myocardial infarction: an intravascular ultrasound study. Circulation 2004; 110: 3424-3429.
67 Vengrenyuk Y, Cardoso L, Weinbaum S. Micro-CT based analysis of a new paradigm for vulnerable plaque rupture: cellular microcalcifications in fibrous caps. Mol Cell Biomech 2008; 05: 37-47.
68 Derlin T, Wisotzki C, Richter U. et al. In Vivo Imaging of Mineral Deposition in Carotid Plaque Using 18F-Sodium Fluoride PET/CT: Correlation with Atherogenic Risk Factors. J Nucl Med March 1 2011; 52: 362-368.
69 Aikawa E, Nahrendorf M, Figueiredo J. et al. Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation 2007; 116: 2841-2850.
70 Zaheer A, Murshed M, De Grand A. et al. Optical imaging of hydroxyapatite in the calcified vasculature of transgenic animals. Arterioscler Thromb Vasc Biol 2006; 26: 1132-1136.
71 Roijers RB, Debernardi N, Cleutjens JP. et al. Microcalcifications in early intimal lesions of atherosclerotic human coronary arteries. Am J Pathol 2011; 178: 2879-2887.
72 Schurgers LJ, Teunissen KJF, Knapen MHJ. et al. Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein: undercarboxylated matrix Gla protein as marker for vascular calcification. Arterioscler Thromb Vasc Biol 2005; 25: 1629-1633.
73 Cranenburg ECM, Koos R, Schurgers LJ. et al. Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species. Thromb Haemost 2010; 104: 811-822.
74 Schurgers LJ, Cranenburg ECM, Vermeer C. Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost 2008; 100: 593-603.
75 Cranenburg ECM, Vermeer C, Koos R. et al. The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification. J Vasc Res 2008; 45: 427-436.
76 Schlieper G, Westenfeld R, Krüger T. et al. Circulating nonphosphorylated carboxylated matrix gla protein predicts survival in ESRD. J Am Soc Nephrol 2011; 22: 387-395.
77 Schurgers LJ, Spronk HMH, Soute BAM. et al. Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats. Blood 2007; 109: 2823-2831.
78 Westenfeld R, Krüger T, Schlieper G. et al. Vitamin K2 supplementation reduces the elevated inactive form of the calcification inhibitor matrix Gla protein in hemodialysis patients. Am Soc Nephrol. 2008 TH-FC044.
79 Yin Z, Huang Z, Cui J. et al. Prothrombotic phenotype of protein Z deficiency. Proc Natl Acad Sci USA 2000; 97: 6734-6738.
80 Jackson CJ, Xue M. Activated protein C - An anticoagulant that does more than stop clots. Int J Biochem Cell Biol 2008; 40: 2692-2697.
81 Vasse M. Protein Z, a protein seeking a pathology. Thromb Haemost 2008; 100: 548-556.
82 Shearer MJ. Role of vitamin K and Gla proteins in the pathophysiology of osteoporosis and vascular calcification. Curr Opin Clin Nutr Metab Care 2000; 03: 433-438.
83 Viegas C, Cavaco S, Neves P. et al. Gla-rich protein is a novel vitamin K-dependent protein present in serum that accumulates at sites of pathological calcifications. Am J Pathol 2009; 175: 2288-2298.
84 Kulman J, Harris J, Haldeman B, Davie E. Primary structure and tissue distribution of two novel proline-rich gamma-carboxyglutamic acid proteins. Proc Natl Acad Sci USA 1997; 94: 9058-9062.
85 Kulman J, Harris J, Xie L, Davie E. Identification of two novel transmembrane gamma-carboxyglutamic acid proteins expressed broadly in fetal and adult tissues. Proc Natl Acad Sci USA 2001; 98: 1370-1375.
86 Rios H, Koushik SV, Wang H. et al. Periostin null mice exhibit dwarfism, incisor enamel defects, and an early-onset periodontal disease-like phenotype. Mol Cell Biol 2005; 25: 11131-11144.
87 Shimazaki M, Nakamura K, Kii I. et al. Periostin is essential for cardiac healing after acute myocardial infarction. J Exp Med 2008; 205: 295-303.