Research Progress of NOS3 Participation in Regulatory Mechanisms of Cardiovascular Diseases_Journal of Biomedical Engineering

Authors：

SUNTing , CHIQingjia ,  WANGGuixue

Key Laboratory of Biorheology and Technology (Chongqing University), Ministry of Education; Chongqing Engineering Laboratory in Vascular Implants; Bioengineering College of Chongqing University, Chongqing 400044, China;

Corresponding author：

WANGGuixue, Email: wanggx@cqu.edu.cn

Keywords：

NOS3; cardiovascular system; uncoupling; epigenetic; polymorphism

DOI：

10.7507/1001-5515.20160034

Video：

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Cardiovascular disease has been a major threat to human’s health and lives for many years. It is of great importance to explore the mechanisms and develop strategies to prevent the pathogenesis. Generally, cardiovascular disease is associated with endothelial dysfunction, which is closely related to the nitric oxide (NO)mediated vasodilatation. The release of NO is regulated by NOS3 gene in mammals’ vascular system. A great deal of evidences have shown that the polymorphism and epigenetic of NOS3 gene play vital roles in the pathological process of cardiovascular disease. To gain insights into the role of NOS3 in the cardiovascular diseases, we reviewed the molecular mechanisms underlying the development of cardiovascular diseases in this paper, including the uncoupling of NOS3 protein, epigenetic and polymorphism of NOS3 gene. The review can also offer possible strategies to prevent and treat cardiovascular diseases.

Citation： SUNTing, CHIQingjia, WANGGuixue. Research Progress of NOS3 Participation in Regulatory Mechanisms of Cardiovascular Diseases. Journal of Biomedical Engineering, 2016, 33(1): 188-192. doi: 10.7507/1001-5515.20160034 Copy

1.	DAFF S. NO synthase: structures and mechanisms [J] . Nitric Oxide, 2010, 23(1): 1-11.
2.	ZHANG Y H, CASADEI B. Sub-cellular targeting of constitutive NOS in health and disease [J] . J Mol Cell Cardiol, 2012, 52(2): 341-350.
3.	F RSTERMANN U, SESSA W C. Nitric oxide synthases: regulation and function [J] . Eur Heart J, 2012, 33(7): 829-837, 37a-37d.
4.	MATTILA J T, THOMAS A C. Nitric oxide synthase: non-canonical expression patterns [J] . Front Immunology, 2014, 5: 478.
5.	XIA N, FORSTERMANN U, LI H. Resveratrol and endothelial nitric oxide [J] . Molecules, 2014, 19(10): 16102-16121.
6.	ANDRADE F A, RESTINI C B, GRANDO M D, et al. Vascular relaxation induced by C-type natriuretic peptide involves the Ca²⁺/NO-synthase/NO pathway [J] . PLoS One, 2014, 9(5): e95446.
7.	BHARATH L P, MUELLER R, LI Y, et al. Impairment of autophagy in endothelial cells prevents shear-stress-induced increases in nitric oxide bioavailability [J] . Can J Physiol Pharmacol, 2014, 92(7): 605-612.
8.	FLEMING I. Molecular mechanisms underlying the activation of eNOS [J] . Pflugers Arch, 2010, 459(6): 793-806.
9.	TIAN X L, LI Y. Endothelial cell senescence and age-relatedvascular diseases [J] . J Genet Genomics, 2014, 41(9): 485-495.
10.	LI H, FORSTERMANN U. Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease [J] . Curr Opin Pharmacol, 2013, 13(2): 161-167.
11.	LI H, HORKE S, FORSTERMANN U. Vascular oxidative stress, nitric oxide and atherosclerosis [J] . Atherosclerosis, 2014, 237(1): 208-219.
12.	CHEN C A, WANG T Y, VARADHARAJ S, et al. S-glutathionylation uncouples eNOS and regulates its cellular and vascular function [J] . Nature, 2010, 468(7327): 1115-1118.
13.	OHTANI K, VLACHOJANNIS G J, KOYANAGI M, et al. Epigenetic regulation of endothelial lineage committed genes in pro-ngiogenic hematopoietic and endothelial progenitor cells [J] . Circ Res, 2011, 109(11): 1219-1229.
14.	BARROSO M, ROCHA M S, ESSE R, et al. Cellular hypomethylation is associated with impaired nitric oxide production by cultured human endothelial cells [J] . Amino Acids, 2012, 42(5): 1903-1911.
15.	KHEIRANDISH-GOZAL L, KHALYFA A, GOZAL D, et al. Endothelial dysfunction in children with obstructive sleep apnea is associated with epigenetic changes in the eNOS gene [J] . Chest, 2013, 143(4): 971-977.
16.	KRAUSE B J, COSTELLO P M, MUNOZ-URRUTIA E, et al. Role of DNA methyltransferase 1 on the altered eNOS expression in human umbilical endothelium from intrauterine growth restricted fetuses [J] . Epigenetics-Us, 2013, 8(9): 944-952.
17.	GODFREY K M, SHEPPARD A, GLUCKMAN P D, et al. Epigenetic gene promoter methylation at birth is associated with child's later adiposity [J] . Diabetes, 2011, 60(5): 1528-1534.
18.	HARVEY N C, LILLYCROP K A, GARRATT E, et al. Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content [J] . Calcified Tissue Int, 2012, 90(2): 120-127.
19.	XU X F, MA X L, SHEN Z, et al. Epigenetic regulation of the endothelial nitric oxide synthase gene in persistent pulmonary hypertension of the newborn rat [J] . J Hypertens, 2010, 28(11): 2227-2235.
20.	WON K J, JUNG S H, JUNG S H, et al. DJ-1/park7 modulates vasorelaxation and blood pressure via epigenetic modification of endothelial nitric oxide synthase [J] . Cardiovasc Res, 2014, 101(3): 473-481.
21.	ZHANG Y G, JIA Q Y, HE Q, et al. The Glu298Asp polymorphism in the NOS3 gene and the risk of prostate cancer [J] . Tumor Biol, 2014, 35(5): 4735-4739.
22.	BRANKOVIC A, BRAJUSKOVIC G, NIKOLIC Z, et al. Endothelial nitric oxide synthase gene polymorphisms and prostate cancer risk in Serbian population [J] . Int J Exp Pathol, 2013, 94(6): 355-361.
23.	ALPOIM P N, GOMES K B, PINHEIRO M D, et al. Polymorphisms in endothelial nitric oxide synthase gene in early and late severe preeclampsia [J] . Nitric Oxide, 2014, 42: 19-23.
24.	CHEN Y, WANG D, ZHOU M, et al. Polymorphisms of the endothelial nitric oxide synthase gene in preeclampsia in a Han Chinese population [J] . Gynecol Obstet Invest, 2014, 77(3): 150-155.
25.	EROZ R, BAHADIR A, DIKICI S, et al. Association of endothelial nitric oxide synthase gene polymorphisms (894G/T, -786T/C, G10T) and clinical findings in patients with migraine [J] . Neuromolecular Medicine, 2014, 16(3): 587-593.
26.	DELLAMEA B S, PINTO L C, LEITAO C B, et al. Endothelial nitric oxide synthase gene polymorphisms and risk of diabetic nephropathy: a systematic review and meta-analysis [J] . BMC Med Genet, 2014, 15: 9.
27.	KALLEL A, SBAI M H, SEDIRI Y, et al. Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian population [J] . Cytokine, 2013, 64(3): 646-651.
28.	JEMAA R, KALLEL A, SEDIRI Y, et al. Association between-786TC polymorphism in the endothelial nitric oxide synthase gene and hypertension in the Tunisian population [J] . Exp Mol Pathol, 2011, 90(2): 210-214.
29.	RISBANO M G, GLADWIN M T. Therapeutics targeting of dysregulated redox equilibrium and endothelial dysfunction [M] // HUMBERT N, EVGENOV O V, STASCH J-P. Pharmacotherapy of pulmonary hypertension. Berlin Heidelberg: Springer, 2013: 315-349.
30.	ROCHETTE L, LORIN J, ZELLER M, et al. Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: possible therapeutic targets? [J] . Pharmacology & Therapeutics, 2013, 140(3): 239-527.

1. DAFF S. NO synthase: structures and mechanisms [J] . Nitric Oxide, 2010, 23(1): 1-11.
2. ZHANG Y H, CASADEI B. Sub-cellular targeting of constitutive NOS in health and disease [J] . J Mol Cell Cardiol, 2012, 52(2): 341-350.
3. F RSTERMANN U, SESSA W C. Nitric oxide synthases: regulation and function [J] . Eur Heart J, 2012, 33(7): 829-837, 37a-37d.
4. MATTILA J T, THOMAS A C. Nitric oxide synthase: non-canonical expression patterns [J] . Front Immunology, 2014, 5: 478.
5. XIA N, FORSTERMANN U, LI H. Resveratrol and endothelial nitric oxide [J] . Molecules, 2014, 19(10): 16102-16121.
6. ANDRADE F A, RESTINI C B, GRANDO M D, et al. Vascular relaxation induced by C-type natriuretic peptide involves the Ca²⁺/NO-synthase/NO pathway [J] . PLoS One, 2014, 9(5): e95446.
7. BHARATH L P, MUELLER R, LI Y, et al. Impairment of autophagy in endothelial cells prevents shear-stress-induced increases in nitric oxide bioavailability [J] . Can J Physiol Pharmacol, 2014, 92(7): 605-612.
8. FLEMING I. Molecular mechanisms underlying the activation of eNOS [J] . Pflugers Arch, 2010, 459(6): 793-806.
9. TIAN X L, LI Y. Endothelial cell senescence and age-relatedvascular diseases [J] . J Genet Genomics, 2014, 41(9): 485-495.
10. LI H, FORSTERMANN U. Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease [J] . Curr Opin Pharmacol, 2013, 13(2): 161-167.
11. LI H, HORKE S, FORSTERMANN U. Vascular oxidative stress, nitric oxide and atherosclerosis [J] . Atherosclerosis, 2014, 237(1): 208-219.
12. CHEN C A, WANG T Y, VARADHARAJ S, et al. S-glutathionylation uncouples eNOS and regulates its cellular and vascular function [J] . Nature, 2010, 468(7327): 1115-1118.
13. OHTANI K, VLACHOJANNIS G J, KOYANAGI M, et al. Epigenetic regulation of endothelial lineage committed genes in pro-ngiogenic hematopoietic and endothelial progenitor cells [J] . Circ Res, 2011, 109(11): 1219-1229.
14. BARROSO M, ROCHA M S, ESSE R, et al. Cellular hypomethylation is associated with impaired nitric oxide production by cultured human endothelial cells [J] . Amino Acids, 2012, 42(5): 1903-1911.
15. KHEIRANDISH-GOZAL L, KHALYFA A, GOZAL D, et al. Endothelial dysfunction in children with obstructive sleep apnea is associated with epigenetic changes in the eNOS gene [J] . Chest, 2013, 143(4): 971-977.
16. KRAUSE B J, COSTELLO P M, MUNOZ-URRUTIA E, et al. Role of DNA methyltransferase 1 on the altered eNOS expression in human umbilical endothelium from intrauterine growth restricted fetuses [J] . Epigenetics-Us, 2013, 8(9): 944-952.
17. GODFREY K M, SHEPPARD A, GLUCKMAN P D, et al. Epigenetic gene promoter methylation at birth is associated with child's later adiposity [J] . Diabetes, 2011, 60(5): 1528-1534.
18. HARVEY N C, LILLYCROP K A, GARRATT E, et al. Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content [J] . Calcified Tissue Int, 2012, 90(2): 120-127.
19. XU X F, MA X L, SHEN Z, et al. Epigenetic regulation of the endothelial nitric oxide synthase gene in persistent pulmonary hypertension of the newborn rat [J] . J Hypertens, 2010, 28(11): 2227-2235.
20. WON K J, JUNG S H, JUNG S H, et al. DJ-1/park7 modulates vasorelaxation and blood pressure via epigenetic modification of endothelial nitric oxide synthase [J] . Cardiovasc Res, 2014, 101(3): 473-481.
21. ZHANG Y G, JIA Q Y, HE Q, et al. The Glu298Asp polymorphism in the NOS3 gene and the risk of prostate cancer [J] . Tumor Biol, 2014, 35(5): 4735-4739.
22. BRANKOVIC A, BRAJUSKOVIC G, NIKOLIC Z, et al. Endothelial nitric oxide synthase gene polymorphisms and prostate cancer risk in Serbian population [J] . Int J Exp Pathol, 2013, 94(6): 355-361.
23. ALPOIM P N, GOMES K B, PINHEIRO M D, et al. Polymorphisms in endothelial nitric oxide synthase gene in early and late severe preeclampsia [J] . Nitric Oxide, 2014, 42: 19-23.
24. CHEN Y, WANG D, ZHOU M, et al. Polymorphisms of the endothelial nitric oxide synthase gene in preeclampsia in a Han Chinese population [J] . Gynecol Obstet Invest, 2014, 77(3): 150-155.
25. EROZ R, BAHADIR A, DIKICI S, et al. Association of endothelial nitric oxide synthase gene polymorphisms (894G/T, -786T/C, G10T) and clinical findings in patients with migraine [J] . Neuromolecular Medicine, 2014, 16(3): 587-593.
26. DELLAMEA B S, PINTO L C, LEITAO C B, et al. Endothelial nitric oxide synthase gene polymorphisms and risk of diabetic nephropathy: a systematic review and meta-analysis [J] . BMC Med Genet, 2014, 15: 9.
27. KALLEL A, SBAI M H, SEDIRI Y, et al. Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian population [J] . Cytokine, 2013, 64(3): 646-651.
28. JEMAA R, KALLEL A, SEDIRI Y, et al. Association between-786TC polymorphism in the endothelial nitric oxide synthase gene and hypertension in the Tunisian population [J] . Exp Mol Pathol, 2011, 90(2): 210-214.
29. RISBANO M G, GLADWIN M T. Therapeutics targeting of dysregulated redox equilibrium and endothelial dysfunction [M] // HUMBERT N, EVGENOV O V, STASCH J-P. Pharmacotherapy of pulmonary hypertension. Berlin Heidelberg: Springer, 2013: 315-349.
30. ROCHETTE L, LORIN J, ZELLER M, et al. Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: possible therapeutic targets? [J] . Pharmacology & Therapeutics, 2013, 140(3): 239-527.

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Research Progress of NOS3 Participation in Regulatory Mechanisms of Cardiovascular Diseases

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