Original Article

Evaluation of Coronary Artery Calcification and Gremlin-1 Serum Level Correlation in Patients with Chronic Ischemic Heart Disease

Abstract

Background: Available evidences have shown that bone morphogenetic proteins (BMPs), particularly BMP 2 and BMP 4, are involved in vascular calcification. Gremlin 1 is one of the important endogenous inhibitors of BMPs. This extracellular antagonist of bone morphogenic proteins has a very complex and cysteine-rich chain and establishes non-colonial transmissions to the members of the family with varying degrees of dependence and prevents them from binding to the receptor, thereby inhibit their function. The main objective of this study was clinical evaluation of the correlation between Gremlin-1 serum concentration and Coronary Artery Calcification.Methods: Eighty-four patients with coronary artery disease from cardiology ward of Razavi Hospital, Mashhad, Iran, who completed the inclusion criteria, entered in the study between November 2015 and March 2016. CT-Angiography was performed to define coronary artery calcium score and Gremlin-1 serum concentrations were measured by an ELISA kit.Results: Eighty-one patients, with mean age of 57.19±10.18 years were included to the study. The mean serum level of Gremlin-1 was 10.92±8.46 pg/mL. There was a reverse significant correlation between Gremlin-1 serum concentration and Coronary Artery Calcification of Right coronary artery(RCA) (P<0.05), in contrast to total Coronary Artery Calcification score, left artery Descending (LAD), Left Main (LM) and Circumflex (CX). However, there was no evidence that age and sex risk factor, hypertension, diabetes mellitus, hyperlipidemia, positive family history, current smoking and high BMI to be associated with serum level of Gremlin-1.Conclusion:  Based on the results, Gremlin-1 serum concentration may be a suitable biomarker for predication coronary artery calcification severity. However, more researches on larger population are necessary for its validation.

1. Santos RD, Nasir K, Carvalho JA, Raqqi P, Blumenthal RS. Coronary calcification and coronary heart disease death rates in different countries, not only the influence of classical risk factors. Atherosclerosis 2009; 202(1): 32-33.
2. Towler DA, Shao JS, Cheng SL, Pingsterhau JM, Loewy AP. Osteogenic regulation of vascular calcification. Ann N Y Acad Sci 2006; 1068: 327-33.
3. Cannata-Andia JB, Rodriguez-Garcia M, Carrillo-Lopez N, Naves-Diaz M, Diaz-Lopez B. Vascular Calcifications: Pathogenesis, Management, and Impact on Clinical Outcomes. J Am Soc Nephrol 2006; 17(12 Suppl 3):S267-73.
4. Abedin M, Tintut Y, Demer LL. Vascular calcification mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol 2004; 24(7): 1161-1170
5. Budoff M J, Achenbach S, Blumenthal RS, et al. Assessment of coronary artery disease by cardiac computed tomography a scientific statement from the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology.Circulation 2006; 114(16): 1761-1791.
6. Arad Y, Spadaro LA, Goodman K, et al. Prediction of coronary events with electron beam computed tomography. J Am Coll Cardiol 2000;36 (4): 1253-60.
7. van der Bijl N, Joemai RM, Geleijns J, et al. Assessment of Agatston coronary artery calcium score using contrast-enhanced CT coronary angiography. AJR Am J Roentgenol. 2010;195 (6): 1299-305. doi:10.2214/AJR.09.3734
8. Nagi D, Lino M, Bendeck MP. Cell-Matrix Interactions and Matricrine Signaling in the Pathogenesis of Vascular Calcification. Front Cardiovasc Med 2018; 5: 174.
9. Abedin M, Tintut Y, Demer, LL. Vascular calcification: mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol 2004; 24, 1161-1170.
10. Katagiri T, Yamaguchi A, Komaki M, Abe E, et al. Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. JCB Home 1994; 127(6), 1755.
11. Hruska KA, Mathew S, Saab G. Bone morphogenetic proteins in vascular calcification. Circ Res 2005; 97, 105-14.
12. Canalis E, Economides AN, Gazzerro E. Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev 2003; 24, 218-35.
13. Maciel TT, Melo RS, Schor N, Campos AH. Gremlin promotes vascular smooth muscle cell proliferation and migration. J Mol Cell Cardiol 2008; 44(2), pp.370-379.
14. Carvajal G, Droguett A, Burgos ME, et al. Gremlin: a novel mediator of epithelial mesenchymal transition and fibrosis in chronic allograft nephropathy. Transplant Proc 2008; 40:734–739.
15. Hsu DR, Economides AN, Wang X, Eimon PM, Harland RM. The xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activites. Mol Cell 1998; 673-683.
16. Gazzerro E, Canalis E. Bone morphogenetic proteins and their antagonists. Rev Endocr Metab Disord 2006; 7(1-2): 51-65.
17. Munoz JC, Martin R, Alonso C, Gurierrez B, Nieto ML. Relation between serum levels of chemotaxis-related factors and the presence of coronary artery calcification as expression of subclinical atherosclerosis. Clin Biochem 2017; 50(18): 1048-1055.
18. Li-Feng G, Jing-kai L, Wai-gaug T. Association of vascular calcification and Gremlin1 expression in radial arteries of patients with stage 5 of chronic kidney disease. Chin J Nephral 2011; 27:807-810.
19. Jara A, Chacon C, Burgos ME. Expression of Gremlin1, a bone morphogenic protein antagonist, is associated with vascular calcification in uremia. J Nephrol Dial Transplant 2009; 1121-1129.
20. Cai J, Pardali E, Sanchez-Duffhue G, Ten Dijke P. BMP Signaling in vascular diseases. FEBS Letters 2012; 586(14):1993-2002.
21. Mullet II, Muller KA, Karathanos A, et al. Impact of Counterbalance Between Macrophage Migration Inhibitory Factor and Its Inhibitor Gremlin-1 in Patients with Coronary Artery Disease. Atherosclerosis 2014; 237(2): 426-432.
22. Park CS, Hong OK, Kim MK, et al. Serum Bone Morphogenic Protein-4 Contributes to Discriminating Coronary Artery Disease Severity. Medicine 2015; 94(39): e1530.
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IssueVol 9, No 2 (Spring 2021) QRcode
SectionOriginal Article(s)
Published2021-06-27
DOI https://doi.org/10.18502/jpc.v9i2.6611
Keywords
Vascular Calcification; Gremlin 1 Protein, Human; Smad Proteins

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How to Cite
1.
Rezapour A, Nazemi S, Mashhadi F, Moallem SMH, Afshar M, Elyasi S, Mohajeri Moghaddam G, Zaerzadeh A, Mohammadpour AH. Evaluation of Coronary Artery Calcification and Gremlin-1 Serum Level Correlation in Patients with Chronic Ischemic Heart Disease. J Pharm Care. 2021;9(2):82-87.