Role of Osteoprotegerin and Its Gene Polymorphisms in the Occurrence of Left Ventricular Hypertrophy in Essential Hypertensive Patients

Overview

Journal Medicine (Baltimore)

Specialty General Medicine

Date 2014 Dec 30

PMID 25546658

Citations 4

Authors

Anna Shen

Xuwei Hou

Deguang Yang

Tingrong Liu

Dezhong Zheng

Liehua Deng

Tao Zhou

Affiliations

Soon will be listed here.

Abstract

The aim of the study was to investigate the role of osteoprotegerin (OPG) in left ventricular hypertrophy (LVH) development in patients with essential hypertension (EH). A total of 1092 patients diagnosed with EH were recruited. The LVHs were determined and OPG gene polymorphisms were genotyped. Patients with LVH had a significantly higher mean serum OPG level than those without LVH. The 1181CC genotype carriers had significantly lower risk for LVH compared with GC and GG genotype carriers. The serum OPG level and OPG 1181 G>C polymorphism were found to be independent risk factors for the occurrence of LVH in hypertensive patients. In vitro study shows that OPG overexpression upregulates cell surface size, protein synthesis per cell, and hypertrophy- and fibrosis-related proteins in both cardiomyocytes and cardiac fibroblasts, whereas OPG inhibition can abolish the above-mentioned changes. Consistent with the in vitro data, our in vivo study revealed that the OPG administration induced the LVH in hypertensive rats. This study is the first to report the close association between OPG and LVH development in EH patients and the regulatory effect of OPG on cardiomyocytes and cardiac fibroblasts.

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References

Liu W, Feng W, Wang F, Li W, Gao C, Zhou B . Osteoprotegerin/RANK/RANKL axis in cardiac remodeling due to immuno-inflammatory myocardial disease. Exp Mol Pathol. 2008; 84(3):213-7. DOI: 10.1016/j.yexmp.2008.02.004. View

Kaufman B, Desai M, Reddy S, Osorio J, Chen J, Mosca R . Genomic profiling of left and right ventricular hypertrophy in congenital heart disease. J Card Fail. 2008; 14(9):760-7. DOI: 10.1016/j.cardfail.2008.06.002. View

Kassan M, Montero M, Sevilla M . Chronic treatment with pravastatin prevents early cardiovascular changes in spontaneously hypertensive rats. Br J Pharmacol. 2009; 158(2):541-7. PMC: 2757694. DOI: 10.1111/j.1476-5381.2009.00339.x. View

Celczynska Bajew L, Horst Sikorska W, Bychowiec B, Wykretowicz A, Wesoly J, Michalak M . The effects of osteoprotegerin (OPG) gene polymorphism in patients with ischaemic heart disease on the morphology of coronary arteries and bone mineral density. Kardiol Pol. 2011; 69(6):573-8. View

Bella J, Goring H . Genetic epidemiology of left ventricular hypertrophy. Am J Cardiovasc Dis. 2012; 2(4):267-78. PMC: 3499934. View

Brandstrom H, Stiger F, Kahan T, Melhus H, Nystrom F, Ohman K . A single nucleotide polymorphism in the promoter region of the osteoprotegerin gene is related to intima-media thickness of the carotid artery in hypertensive patients. The Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol.... Blood Press. 2004; 13(3):152-7. DOI: 10.1080/08037050410035563. View

Morinaga T, Nakagawa N, Yasuda H, Tsuda E, Higashio K . Cloning and characterization of the gene encoding human osteoprotegerin/osteoclastogenesis-inhibitory factor. Eur J Biochem. 1998; 254(3):685-91. DOI: 10.1046/j.1432-1327.1998.2540685.x. View

Xu H, Hou X, Wang L, Wang N, Xu J . Association between transforming growth factor beta1 polymorphisms and left ventricle hypertrophy in essential hypertensive subjects. Mol Cell Biochem. 2009; 335(1-2):13-7. DOI: 10.1007/s11010-009-0235-x. View

Langdahl B, Carstens M, Stenkjaer L, Eriksen E . Polymorphisms in the osteoprotegerin gene are associated with osteoporotic fractures. J Bone Miner Res. 2002; 17(7):1245-55. DOI: 10.1359/jbmr.2002.17.7.1245. View

10.

Hou X, Hu Z, Huang X, Chen Y, He X, Xu H . Serum osteopontin, but not OPN gene polymorphism, is associated with LVH in essential hypertensive patients. J Mol Med (Berl). 2013; 92(5):487-95. DOI: 10.1007/s00109-013-1099-9. View

11.

Schoppet M, Ruppert V, Hofbauer L, Henser S, Al-Fakhri N, Christ M . TNF-related apoptosis-inducing ligand and its decoy receptor osteoprotegerin in nonischemic dilated cardiomyopathy. Biochem Biophys Res Commun. 2005; 338(4):1745-50. DOI: 10.1016/j.bbrc.2005.10.136. View

12.

Schirmer H, Lunde P, Rasmussen K . Prevalence of left ventricular hypertrophy in a general population; The Tromsø Study. Eur Heart J. 1999; 20(6):429-38. DOI: 10.1053/euhj.1998.1314. View

13.

Nielsen O, Sajadieh A . Diagnosing left ventricular hypertrophy in arterial hypertension. BMJ. 2007; 335(7622):681-2. PMC: 2001058. DOI: 10.1136/bmj.39344.470718.BE. View

14.

Kaplinsky E . Significance of left ventricular hypertrophy in cardiovascular morbidity and mortality. Cardiovasc Drugs Ther. 1994; 8 Suppl 3:549-56. DOI: 10.1007/BF00877223. View

15.

Olesen M, Skov V, Mechta M, Mumm B, Rasmussen L . No influence of OPG and its ligands, RANKL and TRAIL, on proliferation and regulation of the calcification process in primary human vascular smooth muscle cells. Mol Cell Endocrinol. 2012; 362(1-2):149-56. DOI: 10.1016/j.mce.2012.06.004. View

16.

Valera E, Brassesco M, Scrideli C, Barros M, Santos A, Oliveira R . Are patients with encephalocraniocutaneous lipomatosis at increased risk of developing low-grade gliomas?. Childs Nerv Syst. 2011; 28(1):19-22. DOI: 10.1007/s00381-011-1601-z. View

17.

Brandstrom H, Stiger F, Lind L, Kahan T, Melhus H, Kindmark A . A single nucleotide polymorphism in the promoter region of the human gene for osteoprotegerin is related to vascular morphology and function. Biochem Biophys Res Commun. 2002; 293(1):13-7. DOI: 10.1016/S0006-291X(02)00137-7. View

18.

Ozawa M, Tamura K, Okano Y, Matsushita K, Ikeya Y, Masuda S . Blood pressure variability as well as blood pressure level is important for left ventricular hypertrophy and brachial-ankle pulse wave velocity in hypertensives. Clin Exp Hypertens. 2009; 31(8):669-79. DOI: 10.3109/10641960903407033. View

19.

El-Shehaby A, El-Khatib M, Marzouk S, Battah A . Relationship of BsmI polymorphism of vitamin D receptor gene with left ventricular hypertrophy and atherosclerosis in hemodialysis patients. Scand J Clin Lab Invest. 2012; 73(1):75-81. DOI: 10.3109/00365513.2012.743163. View

20.

Su F, Shi M, Guo W, Liu X, Wang H, Lu Z . High-mobility group box 1 induces calcineurin-mediated cell hypertrophy in neonatal rat ventricular myocytes. Mediators Inflamm. 2012; 2012:805149. PMC: 3388313. DOI: 10.1155/2012/805149. View