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Is circulating Gla-rich protein linked with coronary calcium and cardiovascular pathology in patients with atrial fibrillation or heart failure? A pilot study

Deyana Vankova, Milena Pasheva, Atanas Angelov, Yoto Yotov, Bistra Galunska

Abstract

Introduction: Nowadays Gla-rich protein (GRP) is recognized as a novel biomarker playing a pivotal role in the crosstalk between chronic inflammation and vascular calcification.

Aim: The aim of this article is to study the link between circulating GRP, cardiovascular pathology, and the degree of arterial calcification evaluated by the coronary arterial calcium score (CACS) in a Bulgarian population sample.

 

Materials and Methods: Adult participants (n = 81) of both genders were divided into: controls (n = 41)—subjects with estimated moderate-to-high risk without known cardiovascular diseases (CVDs) and a combined CVD group (n = 40)—patients with paroxysmal or persistent atrial fibrillation in sinus rhythm, and heart failure subjects with preserved ejection fraction. A structured interview was carried out for evaluation of the classical CVD risk factors. CACS was determined by multislice computed tomography. Routine laboratory parameters were extracted from medical records. Serum levels of total GRP, matrix Gla protein, and osteocalcin were estimated by commercial ELISA kits. Standard statistical methods (descriptive statistics, Student’s t-test and Spearman’s correlation) were applied. Statistical significance was considered at p<0.05.

 

Results: Significantly lower GRP levels were established in patients with coronary calcium compared to those without calcium deposits. Clear tendency for decreased levels of GRP was observed in the combined CVD group vs controls. Circulating GRP significantly correlates with uncarboxylated matrix Gla protein. An association between serum GRP, CRP, and low-density lipoproteins (LDLs) was demonstrated.

 

Conclusion: This study adds new information regarding the role of circulating GRP as a new player in calcification inhibition. Our findings illuminate the link between total circulating GRP, CVD pathology, and the degree of coronary calcification.


Keywords

Gla rich protein (GRP), coronary arterial calcium score (CACS), atrial fibrillation, heart failure

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References

Roumeliotis S, Dounousi A, Salmas M, Elefteriadis T, Liakopoulos V. Vascular calcification in chronic kidney disease: the role of vitamin K- dependent matrix Gla protein. Front Med. 2020;7:154. doi: 10.3389/fmed.2020.00154.

Viegas C, Araújo N, Marreiros C, Simes D. The interplay between mineral metabolism, vascular calcification and inflammation in Chronic Kidney Disease (CKD): Challenging old concepts with new facts. Aging, 2019;11(12):4274–99. doi: 10.18632/aging.102046.

Nelson AJ, Raggi P, Wolf M, Gold A, Chertow G, Roe MT. Targeting vascular calcification in chronic kidney disease. J Am Coll Cardiol Basic Transl Science. 2020; 5(4):398–412. doi: 10.1016/j.jacbts.2020.02.002.

Surmann-Schmitt C, Dietz U, Kireva T, Adam N, Park J, Tagariello A, et al. Ucma, a novel secreted cartilage-specific protein with implications in osteogenesis. J Biol Chem. 2008;283(11):7082–93. doi: 10.1074/jbc.M702792200.

Viegas CS, Simes DC, Laizé V, Williamson MK, Price PA, Cancela ML. Gla-rich protein (GRP), a new vitamin K-dependent protein identified from sturgeon cartilage and highly conserved in vertebrates. J Biol Chem. 2008;283(52):36655–64. doi: 10.1074/jbc.M802761200.

Viegas CS, Rafael MS, Enriquez JL, Teixeira A, Vitorino R, Luís IM, et al. Gla-rich protein acts as a calcification inhibitor in the human cardiovascular system. Arterioscler Thromb Vasc Biol. 2015;35(2):399–408. doi: 10.1161/ATVBAHA.114.304823.

Viegas CS, Santos L, Macedo AL, Matos AA, Silva, AP, Neves PL, et al. Chronic kidney disease circulating calciprotein particles and extracellular vesicles promote vascular calcification: A role for GRP (Gla-rich protein). Arterioscler Thromb Vasc Biol. 2018; 38(3):575–87. doi: 10.1161/ATVBAHA.117.310578.

Cavaco S, Viegas CS, Rafael MS, Ramos A, Magalhães J, Blanco FJ, et al. Gla-rich protein is involved in the cross-talk between calcification and inflammation in osteoarthritis. Cell Mol Life Sci. 2015;73(5):1051–65. doi: 10.1007/s00018-015-2033-9.

Willems BA, Vermeer C, Reutelingsperger CP, Schurgers LJ. 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.

Luo G, Ducy P, Mckee MD, Pinero GJ, Loyer E, Behringer RR, et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix Gla protein. Nature. 1997;386(6620):78–81. doi: 10.1038/386078a0.

Viegas CS, Herfs M, Rafael MS, Enriquez JL, Teixeira A, Luís IM, et al. Gla-rich protein is a potential new vitamin K target in cancer: evidences for a direct GRP–mineral interaction. Biomed Res Int. 2014;2014:340216. doi: 10.1155/2014/340216.

Rafael MS, Cavaco S, Viegas CS, Santos S, Ramos A, Willems B, et al. Insights into the association of Gla-rich protein (GRP) and osteoarthritis: novel splice variants and γ-carboxylation status. Mol Nutr Food Res. 2014;58(8):1636–46. doi: 10.1002/mnfr.201300941.

Piepoli MF, Hoes A, Agewall S, Albus C, Brotons C, Catapano A, et al. European Guidelines on cardiovascular disease prevention in clinical practice: The sixth joint task force of the European society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts). Developed with the special contribution of the European association for cardiovascular prevention & Rehabilitation (EACPR). Eur Heart J.2016; 37(29):2315–81. doi: 10.1093/eurheartj/ehw106.

Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15(4):827–32. doi: 10.1016/0735-1097(90)90282-t.

Dalmeijer GW, van der Schouw Y, Magdeleyns E, Vermeer C, Elias S, Velthuiset B, et al. Circulating species of matrix Gla protein and the risk of vascular calcification in healthy women. Int J Cardiol. 2013;168(6):e168–70. doi: 10.1016/j.ijcard.2013.08.062.

Willems BA, Furmanik M, Caron MM, Chatrou ML, Kusters DH, Welting TJ, et al. Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signaling. Sci Rep. 2018;8(1):4961. doi: 10.1038/s41598-018-23353-y.

Silva AP, Viegas CS, Mendes F, Macedo A, Guilherme P, Tavares N. Gla-Rich protein (GRP) as an early and novel marker of vascular calcification and kidney dysfunction in diabetic patients with CKD: A pilot cross-sectional study. J Clin Med. 2020;9(3):635. doi: 10.3390/jcm9030635.

Shroff R, Long DA, Shanahan C. Mechanistic insights into vascular calcification in CKD. J Am Soc Nephrol. 2013;24(2):179–89. doi: 10.1681/ASN.2011121191.

Viegas CS, Cavaco S, Neves PL, Ferreira A, João A, Williamson MK, 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(6):2288–98. doi: 10.2353/ajpath.2009.090474.

Ueland T, Gullestad L, Dahl CP, Aukrust P, Aakhus S, Solberg OG, et al. Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis. J Intern Med. 2010;268(5):483–92. doi: 10.1111/j.1365-2796.2010.02264.x.




DOI: http://dx.doi.org/10.14748/ssm.v0i0.7374
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About The Authors

Deyana Vankova
Medical University of Varna
Bulgaria

Department of Biochemistry, Molecular Medicine and Nutrigenomics, Faculty of Pharmacy

Milena Pasheva
Medical University of Varna
Bulgaria

Department of Biochemistry, Molecular Medicine and Nutrigenomics, Faculty of Pharmacy

Atanas Angelov
Medical University of Varna
Bulgaria

First Department of Internal Diseases, Faculty of Medicine

Yoto Yotov
Medical University of Varna
Bulgaria

First Department of Internal Diseases, Faculty of Medicine

Bistra Galunska
Medical University of Varna
Bulgaria

Department of Biochemistry, Molecular Medicine and Nutrigenomics, Faculty of Pharmacy

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