Desphospho-Uncarboxylated Matrix-Gla Protein Is Increased Postoperatively in Cardiovascular Risk Patients

Overview

Journal Nutrients

Date 2018 Jan 6

PMID 29303985

Citations 8

Authors

Sofia Dahlberg

Jacob Ede

Leon Schurgers

Cees Vermeer

Thomas Kander

Bengt Klarin

Ulf Schott

Affiliations

Soon will be listed here.

Abstract

Background: Matrix Gla protein (MGP) is an extrahepatic protein that is dependent on glutamate carboxylation, a vitamin K-dependent process. Its dysfunctional form, desphospho-uncarboxylated-MGP, has been associated with increased arterial calcification and stiffness. The aim of this study was to measure the degree of postoperative carboxylation of MGP and two other Gla proteins in patients scheduled for abdominal or orthopaedic surgery.

Methods: Forty patients undergoing abdominal or orthopaedic surgery were included. Blood samples were collected preoperatively and four days after the surgery. Desphospho-carboxylated MGP (dp-cMGP), desphospho-uncarboxylated MGP (dp-ucMGP), carboxylated osteocalcin (OC) (cOC), uncarboxylated OC (ucOC), and uncarboxylated prothrombin (PIVKA-II) were analysed.

Results: Preoperatively, 29 patients had dp-ucMGP levels above the reference values. Patients with pre-existing cardiovascular comorbidities had higher dp-ucMGP preoperatively compared with patients with no record of cardiovascular disease. Postoperatively, this number increased to 36 patients, and median dp-ucMGP levels increased ( < 0.0001) and correlated to a PIVKA-II increase ( = 0.44). On the other hand, dp-cMGP levels did not significantly alter. Decreased levels of ucOC and cOC were seen after surgery ( = 0.017 and = 0.0033, respectively). Comorbidities, possible nutritional defects, and complications affecting Gla protein activity and function were identified.

Conclusions: Dp-ucMGP was high preoperatively, and had further increased postoperatively. This pattern was linked to several comorbidities, possible nutritional defects, and postoperative complications, which motivates further research about potential interactions between perioperative corrective treatments with vitamin K supplements, cardiovascular biomarkers, and incidents of stroke and myocardial infarction events.

Citing Articles

Vitamin K1 Administration Increases the Level of Circulating Carboxylated Osteocalcin in Critically Ill Patients.

Aydin N, Kander T, Schott U, Hafizi S Nutrients. 2025; 17(2.

PMID: 39861478 PMC: 11768845. DOI: 10.3390/nu17020348.

Extrahepatic Vitamin K-Dependent Gla-Proteins-Potential Cardiometabolic Biomarkers.

Galunska B, Yotov Y, Nikolova M, Angelov A Int J Mol Sci. 2024; 25(6).

PMID: 38542487 PMC: 10971439. DOI: 10.3390/ijms25063517.

The biological responses of vitamin K2: A comprehensive review.

Yan Q, Zhang T, OConnor C, Barlow J, Walsh J, Scalabrino G Food Sci Nutr. 2023; 11(4):1634-1656.

PMID: 37051359 PMC: 10084986. DOI: 10.1002/fsn3.3213.

Vitamin K Effects on Gas6 and Soluble Axl Receptors in Intensive Care Patients: An Observational Screening Study.

Schott U, Augustsson C, Lilover L, Ulfsdotter Nilsson C, Walther-Sturesson L, Kander T Nutrients. 2021; 13(11).

PMID: 34836355 PMC: 8621311. DOI: 10.3390/nu13114101.

Hepatic and Vascular Vitamin K Status in Patients with High Cardiovascular Risk.

Rapp N, Brandenburg V, Kaesler N, Bakker S, Stohr R, Schuh A Nutrients. 2021; 13(10).

PMID: 34684491 PMC: 8539359. DOI: 10.3390/nu13103490.

References

Nimptsch K, Rohrmann S, Kaaks R, Linseisen J . Dietary vitamin K intake in relation to cancer incidence and mortality: results from the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am J Clin Nutr. 2010; 91(5):1348-58. DOI: 10.3945/ajcn.2009.28691. View

Willems B, Vermeer C, Reutelingsperger C, Schurgers L . The realm of vitamin K dependent proteins: shifting from coagulation toward calcification. Mol Nutr Food Res. 2014; 58(8):1620-35. DOI: 10.1002/mnfr.201300743. View

Ferland G, Sadowski J, OBrien M . Dietary induced subclinical vitamin K deficiency in normal human subjects. J Clin Invest. 1993; 91(4):1761-8. PMC: 288156. DOI: 10.1172/JCI116386. View

Sokoll L, Sadowski J . Comparison of biochemical indexes for assessing vitamin K nutritional status in a healthy adult population. Am J Clin Nutr. 1996; 63(4):566-73. DOI: 10.1093/ajcn/63.4.566. View

Wei F, Drummen N, Schutte A, Thijs L, Jacobs L, Petit T . Vitamin K Dependent Protection of Renal Function in Multi-ethnic Population Studies. EBioMedicine. 2016; 4:162-9. PMC: 4776057. DOI: 10.1016/j.ebiom.2016.01.011. View

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(5):625-30. PMC: 2172384. DOI: 10.1083/jcb.200402046. View

Chen Z, Qureshi A, Parini P, Hurt-Camejo E, Ripsweden J, Brismar T . Does statins promote vascular calcification in chronic kidney disease?. Eur J Clin Invest. 2016; 47(2):137-148. DOI: 10.1111/eci.12718. View

Mayer Jr O, Seidlerova J, Bruthans J, Filipovsky J, Timoracka K, Vanek J . Desphospho-uncarboxylated matrix Gla-protein is associated with mortality risk in patients with chronic stable vascular disease. Atherosclerosis. 2014; 235(1):162-8. DOI: 10.1016/j.atherosclerosis.2014.04.027. View

Mayer Jr O, Seidlerova J, Wohlfahrt P, Filipovsky J, Vanek J, Cifkova R . Desphospho-uncarboxylated matrix Gla protein is associated with increased aortic stiffness in a general population. J Hum Hypertens. 2015; 30(7):418-23. DOI: 10.1038/jhh.2015.55. View

10.

Grosley B, Hirschauer C, CHAMBRETTE B, Bezeaud A, Amiral J . Specific measurement of hypocarboxylated prothrombin in plasma or serum and application to the diagnosis of hepatocellular carcinoma. J Lab Clin Med. 1996; 127(6):553-64. DOI: 10.1016/s0022-2143(96)90146-8. View

11.

Cranenburg E, Schurgers L, Vermeer C . Vitamin K: the coagulation vitamin that became omnipotent. Thromb Haemost. 2007; 98(1):120-5. View

12.

Dahlberg S, Ede J, Schott U . Vitamin K and cancer. Scand J Clin Lab Invest. 2017; 77(8):555-567. DOI: 10.1080/00365513.2017.1379090. View

13.

Liu Y, Gu Y, Thijs L, Knapen M, Salvi E, Citterio L . Inactive matrix Gla protein is causally related to adverse health outcomes: a Mendelian randomization study in a Flemish population. Hypertension. 2014; 65(2):463-70. DOI: 10.1161/HYPERTENSIONAHA.114.04494. View

14.

Ueland T, Dahl C, Gullestad L, Aakhus S, Broch K, Skardal R . Circulating levels of non-phosphorylated undercarboxylated matrix Gla protein are associated with disease severity in patients with chronic heart failure. Clin Sci (Lond). 2011; 121(3):119-27. DOI: 10.1042/CS20100589. View

15.

Dalmeijer G, van der Schouw Y, Magdeleyns E, Vermeer C, Verschuren W, Boer J . Matrix Gla protein species and risk of cardiovascular events in type 2 diabetic patients. Diabetes Care. 2013; 36(11):3766-71. PMC: 3816877. DOI: 10.2337/dc13-0065. View

16.

Caluwe R, Pyfferoen L, De Boeck K, De Vriese A . The effects of vitamin K supplementation and vitamin K antagonists on progression of vascular calcification: ongoing randomized controlled trials. Clin Kidney J. 2016; 9(2):273-9. PMC: 4792621. DOI: 10.1093/ckj/sfv146. View

17.

Luo G, Ducy P, McKee M, Pinero G, Loyer E, Behringer R . Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature. 1997; 386(6620):78-81. DOI: 10.1038/386078a0. View

18.

Torgersen Z, Balters M . Perioperative nutrition. Surg Clin North Am. 2015; 95(2):255-67. DOI: 10.1016/j.suc.2014.10.003. View

19.

Thomas O, Rein H, Strandberg K, Schott U . Coagulative safety of epidural catheters after major upper gastrointestinal surgery: advanced and routine coagulation analysis in 38 patients. Perioper Med (Lond). 2016; 5:28. PMC: 5067910. DOI: 10.1186/s13741-016-0053-0. View

20.

Vossen L, Schurgers L, van Varik B, Kietselaer B, Vermeer C, Meeder J . Menaquinone-7 Supplementation to Reduce Vascular Calcification in Patients with Coronary Artery Disease: Rationale and Study Protocol (VitaK-CAC Trial). Nutrients. 2015; 7(11):8905-15. PMC: 4663571. DOI: 10.3390/nu7115443. View