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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2002; 48(6): 86-102

PATHOPHYSIOLOGICAL ASPECTS OF ENDOTHELIAL NO-SYNTASE GENETIC POLYMORPHYSM

V.E. Dosenko, V.Yu. Zagoriy, A.A. Moibenko, A.N. Parchomenko

    Bogomoletz Institute of Physiology, National Academy of Science, Kiev, Ukraine



Abstract

Information about fourteen allelic variants of promoter, exons and introns of a gene of endothelial NO-synhase (eNOS) dealing with their role in a susceptibility to cardio-vascular diseases has been reviewed. Data of the populational genetic studies, performed in different regions of the world, were analysed to show the interrelation between an availability of on allele in the genome and a risk of ischemic heart desease. The main attention was focussed on the clarification of a relation between some allelic variants of the gene and functional (biochemical) properties of the protein, encoded by this gene, as well as on two principal mechanisms of realization of the pathological allelic variants in eNOS gene: 1) forming the protein in an insufficient quantity or with an altered activity (an interrupted transcription, and stability of informational RNA, formation of a catalitically deficient protein); 2) an increased protein degradation (due to an acidic hydrolysis or an enhanced proteasomal proteolysis). In practical aspect, the most important problem, according to the point of view of the authors, is that of searching the pharmaco-therapeutical remedies, able to influence the different stages of the molecularbiological realization of an altered eNOS gene (transcription, translation, posttranslational modifications and degradation). Clarification of the obove pathogenetic mechanisms will open broad perspectives in constructing therapeutical schemes for individuals possessing the pathological alleles of this gene.

Keywords: GENETIC POLYMORPHYSM

Full text: (PDF, in Ukrainian)

References

    Áó泺âñüêà Ò.². Îñíîâè ìåäè÷íî¿ ãåíåòèêè. Ê.: – Çäîðîâ’ÿ, 2001. – 126 ñ. 2. Ãîðáóíîâà Â.Í., Áàðàíîâ Â.Ñ. Ââåäåíèå â ìîëåêó- ëÿðíóþ äèàãíîñòèêó è ãåíîòåðàïèþ íàñëåäñòâåííûõ çàáîëåâàíèé. – ÑÏá.: Ñïåö. ëèòåðàòóðà, 1997. – 287 ñ. 3. Màëûøåâ È.Þ., Ìîíàñòûðñêàÿ Å.A., Ñìèðèí Á.Â., Ìàíóõèíà E.Á. Ãèïîêñèÿ è îêñèä àçîòà // Âåñòí. Ðîñ. Aêàä. ìeä. íàóê. – 2000, ¹9. – Ñ.44 – 48. 4. Ìîéáåíêî Î.Î., Ïàâëþ÷åíêî Â.Á., Äàöåíêî Â.Â. è äð. Äîñë³äæåííÿ ðîë³ åíäîòåë³éçàëåæíèõ ôàêòîð³â ó ðåàë³çàö³¿ êàðä³îãåííèõ ðåôëåêñ³â çà íîðìàëüíèõ òà ïàòîëîã³÷íèõ óìîâ // Ô³ç³îë. æóðí. – 2000. – 46, ¹2. – Ñ.19 – 32. 5. Moéáåíêî Î.Î., Ñàãà÷ Â.Ô., Øàïîâàë Ë.Ì. òà ³í. Ðîëü åíäîòåë³þ òà á³îëîã³÷íî-àêòèâíèõ ðå÷îâèí åíäî- òåë³àëüíîãî ïîõîäæåííÿ â ðåãóëÿö³¿ êðîâîîá³ãó òà ä³ÿëüíîñò³ ñåðöÿ // Òàì ñàìî. – 1997. – 43, ¹ 1 – 2. – Ñ.3 – 18. 6. Ìóñòàôèíà Î.Å., Øàãèñóëòàíîâà Å.È., Íàñèáóëëèí Ò.Ð. è äð. Ìèêðîñàòåëëèòíûé ïîëèìîðôèçì ãåíà åíäîòåëèàëüíîé NO-ñèíòàçû: èññëåäîâàíèÿ ïîïó- ëÿöèé Âîëãî-Óðàëüñêîãî ðåãèîíà è àíàëèç ñâÿçè ñ èíôàðêòîì ìèîêàðäà è ýññåíöèàëüíîé ãèïåðòåíçèåé // Ãåíåòèêà. – 2001. – 37, N5. – Ñ.668 – 674. 7. Ðåóòîâ B.Ï., Ñîðîêèíà Å.Ã., Îõîòèí Â.Å., Êîñèöûí Í.Ñ. Öèêëè÷åñêèå ïðåâðàùåíèÿ îêñèäà àçîòà â îðãàíèçìå ìëåêîïèòàþùèõ. – Ì.: Íàóêà, 1998. – 159 ñ. 8. Ñàãà÷ Â.Ô., Ñîëîâéîâ À.²., Áàçèëþê Î.Â. òà ³í. Åíäîòåë³éçàëåæí³ ñóäèíí³ ðåàêö³¿ ó êðîëèê³â ï³ä ÷àñ òðèâàëî¿ åêñïåðèìåíòàëüíî¿ ã³ïåðõîëåñòåðèíå쳿 // Ô³ç³îë. æóðí. – 1994. – 40, ¹2. – Ñ.73 – 82. 9. Ñèíãåð Ì., Áåðã Ï. Ãåíû è ãåíîìû. – Ì.: Ìèð, 1998. – Ò.1. – 373 ñ; Ò.2. – 391 ñ. 10. Alderton W.K., Cooper C.E., Knowles R.G. Nitric oxide synthases: structure, function and inhibition // Biochem. J. – 2001. – 357. – P.593 – 615. 11. Alvarez R., Gonzalez P., Batalla A. et al. Association between the NOS3 (-786 T/C) and the ACE (I/D) DNA genotypes and early coronary artery disease // Nitric Oxide. – 2001. – 5, N4. – P.343 – 348. 12. Arnet U.A., McMillan A., Dinerman J.L. et al. Regulation of endothelial nitric-oxide synthase during hypoxia // J. Biol. Chem. – 1996. – 271, N25. – P.15069 – 15073. 13. Belhassen L., Feron O., Kaye D.M. et al. Regulation by cAMP of post – translational processing and subcellular targeting of endothelial nitric–oxide synthase (type 3) in cardiac myocytes // J. Biol. Chem. – 1997. – 272, N17. – P.11198 – 11204. Benjafield A.V., Morris B.J. Association analyses of endothelial nitric oxide synthase gene polymorphisms in essential hypertension // Amer. J. Hypertens. – 2000. – 13, N9. – P.994 – 998. 15. Bennett M.R., Macdonald K., Chan S.W. et al. Cooperative interactions between RB and p53 regulate cell proliferation, cell senescence, and apoptosis in human vascular smooth muscle cells from atherosclerotic plaques // Circulat. Res. – 1998. – 82, N6. – P.704 – 712. 16. Billcke S.S., Bender A.T., Kanelakis K.C. et al. Hsp90 is required for heme binding and activation of apo–neuronal nitric – oxide synthase: geldanamycin – mediated oxidant generation is unrelated to any action of Hsp90 // J. Biol. Chem. – 2002. – 277, N23. – P.20504 – 20509. 17. Brouet A., Sonveaux P., Dessy C. et al. Hsp90 and caveolin are key targets for the proangiogenic nitric oxide– mediated effects of statins // Circulat. Res. – 2001. – 89, N10. – P.866 – 873. 18. Campbell B., Adams J., Shin Y.K., Lefer A.M. Cardioprotective effects of a novel proteasome inhibitor following ischemia and reperfusion in the isolated perfused rat heart // J. Mol. Cell Cardiol. – 1999. – 31, N2. – P.467 – 476. 19. Chen W., Srinivasan S.R., Elkasabany A. et al. Combined effects of endothelial nitric oxide synthase gene polymorphism (G894T) and insulin resistance status on blood pressure and familial risk of hypertension in young adults: the Bogalusa Heart Study // Amer. J. Hypertens. – 2001. – 14, N10. – P.1046 – 1052. 20. Chu Y., Heistad D.D., Knudtson K.L. et al. Quantification of mRNA for endothelial NO synthase in mouse blood vessels by real–time polymerase chain reaction // Arterioscler. Thromb. Vasc. Biol. – 2002. – 22, N4. – P.611 – 616. 21. Colombo M.G., Andreassi M.G., Paradossi U. et al. Evidence for association of a common variant of the endothelial nitric oxide synthase gene (Glu298 —>Asp polymorphism) to the presence, extent, and severity of coronary artery disease // Heart. – 2002. – 87, N6. – P.525 – 528. 22. Drummond G.R., Cai H., Davis M.E. et al. Transcriptional and posttranscriptional regulation of endothelial nitric oxide synthase expression by hydrogen peroxide // Circulat. Res. – 2000. – 86, N3. – P.347 – 354. 23. Du X.L., Edelstein D., Dimmeler S. et al. Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site // J. Clin. Invest. – 2001. – 108, N9. – P.1341 – 1348. 24. Duplain H., Burcelin R., Sartori C. et al. Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase // Circulation. – 2001. – 104, N3. – P.342 – 345. 25. Fairchild T.A., Fulton D., Fontana J.T. et al. Acidic hydrolysis as a mechanism for the cleavage of the Glu(298) —>Asp variant of human endothelial nitric – oxide synthase // J. Biol. Chem. – 2001. – 276, N28. – P.26674 – 26679. 26. Felley–Bosco E., Bender F.C., Courjault–Gautier F. et al. Caveolin–1 downregulates inducible nitric oxide synthase via the proteasome pathway in human colon carcinoma cells // Proc. Natl. Acad. Sci. USA. – 2000. – 97. – P.14334 – 14339. 27. Feron O., Dessy C., Opel D.J. et al. Modulation of the endothelial nitric oxide synthase – caveolin interaction in cardiac myocytes // J. Biol. Chem. – 1998. – 273, N46. – P.30249 – 30254. 28. Freedman J.E., Sauter R., Battinelli E.M. et al. Deficient platelet–derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene // Circulat. Res. – 1999. – 84, N12. – P.1416 – 1421. 29. Fulton D., Gratton J.P., Sessa W.C. Post–translational control of endothelial nitric oxide synthase: why isn’t calcium/calmodulin enough? // J. Pharmacol. Exp. Therap. – 2001. – 299, N3. – P.818 – 824. 30. Furchgott R.F. Role of endothelium in response of vascular smooth muscle // Circulat. Res. – 1983. – 53. – P.557 – 573. 31. Furchogott R.F. Studies on endothelium-dependent vasodilatation and the endothelium–derived relaxing factor / / Acta Physiol. Scand. – 1990. – 139. – P.157 – 270. 32. Garcia-Ñardena G., Martasek P., Masters B. et al. Dissecting the interaction between nitric oxide synthase and caveolin // J. Biol. Chem. – 1997. – 272, N41. – P.25437 – 25440. 33. Gardemann A., Lohre J., Cayci S. et al. The T allele of the missense Glu(298)Asp endothelial nitric oxide synthase gene polymorphism is associated with coronary heart disease in younger individuals with high atherosclerotic risk profile // Atherosclerosis. – 2002. – 160, N1. – P.167 – 175. 34. Geng Y.J. Regulation of programmed cell death or apoptosis in atherosclerosis // Heart and Vessels. – 1997, Suppl 12. – P.76 – 80. 35. Govers R., Rabelink T.J. Cellular regulation of endothelial nitric oxide synthase // Amer. J. Physiol. Renal. Physiol. – 2001. – 280, N2. – P.193 – 206. 36. Granath B., Taylor R.R., van Bockxmeer F.M., Mamotte C.D. Lack of evidence for association between endothelial nitric oxide synthase gene polymorphisms and coronary artery disease in the Australian Caucasian population // J. Cardiovasc. Risk. – 2001. – 8, N4. – P.235 – 241. 37. Guzik T.J., Black E., West N.E. et al. Relationship between the G894T polymorphism (Glu298Asp variant) in endothelial nitric oxide synthase and nitric oxide–mediated endothelial function in human atherosclerosis // Amer. J. Med. Genet. – 2001. – 100, N2. – P.130 – 137. 38. Hannon G.J. RNA interference // Nature. – 2002. – 418. – P.244 – 251. 39. Hara K., Kobayashi N., Watanabe S. et al. Effects of quinapril on expression of eNOS, ACE, and AT1 receptor in deoxycorticosterone acetate – salt hypertensive rats // Amer. J. Hypertens. – 2001. – 14, N4, Pt1. – P.321 – 330. Hibi K., Ishigami T., Tamura K. et al. Endothelial nitric oxide synthase gene polymorphism and acute myocardial infarction // Hypertension. – 1998. – 32, N3. – P.521 – 526. 41. Hingorani A.D., Liang C.F., Fatibene J. et al. A common variant of the endothelial nitric oxide synthase (Glu298 —>Asp) is a major risk factor for coronary artery disease in the UK // Circulation. – 1999. – 100, N14. – P.1515 – 1520. 42. Hwang J.J., Tsai C.T., Yeh H.M. et al. The 27-bp tandem repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene is not associated with coronary artery disease in a hospital – based Taiwanese population // Cardiology. – 2002. – 97, N2. – P.67 – 72. 43. Jachymova M., Horky K., Bultas J. et al. Association of the Glu298Asp polymorphism in the endothelial nitric oxide synthase gene with essential hypertension resistant to conventional therapy // Biochem. and Biophys. Res. Commun. – 2001. – 284, N2. – P.426 – 430. 44. Kajiyama N., Saito Y., Miyamoto Y. Et al. Lack of association between T–786 —>C mutation in the 5' – flanking region of the endothelial nitric oxide synthase gene and essential hypertension // Hypertens. Res. – 2000. – 23, N6. – P.561 – 565. 45. Karvonen J., Kauma H., Kervinen K. et al. Endothelial nitric oxide synthase gene Glu298Asp polymorphism and blood pressure, left ventricular mass and carotid artery atherosclerosis in a population-based cohort // J. Intern. Med. – 2002. – 251, N2. – P.102 – 110. 46. Kim Y.M., Bombeck C.A., Billiar T.R. Nitric oxide as a bifunctional regulator of apoptosis // Circulat. Res. – 1999. – 84. – P.253 – 256. 47. Kishi T., Hirooka Y., Sakai K. et al. Overexpression of eNOS in the RVLM causes hypotension and bradycardia via GABA release // Hypertension. – 2001. – 38, N4. – P.896 – 901. 48. Kojda G., Cheng Y.C., Burchfield J., Harrison D.G. Dysfunctional regulation of endothelial nitric oxide synthase (eNOS) expression in response to exercise in mice lacking one eNOS gene // Circulation. – 2001. – 103, N23. – P.2839 – 2844. 49. Krichevsky A.M., Kosik K.S. RNAi functions in cultured mammalian neurons // Proc. Natl. Acad. Sci. USA. – 2002. – 99. – N18. – P. 11926 – 11929. 50. Kubota I., Han X., Opel D.J. et al. Increased susceptibility to development of triggered activity in myocytes from mice with targeted disruption of endothelial nitric oxide synthase // J. Mol. Cell. Cardiol. – 2000. – 32, N7. – P.1239 – 1248. 51. Lacolley P., Gautier S., Poirier O. et al. Nitric oxide synthase gene polymorphisms, blood pressure and aortic stiffness in normotensive and hypertensive subjects // J. Hypertens. – 1998. – 16, N1. – P.31 – 35. 52. Laufs U., Gertz K., Huang P. et al. Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice // Stroke. – 2000. – 31, N10. – P.2442 – 2449. 53. Laufs U., Liao J.K. Post – transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase // J. Biol. Chem. – 1998. – 273, N37. – P.24266 – 24271. 54. Leeson C.P.M., Hingorani A.D., Mullen M.J. et al. Glu298Asp endothelial nitric oxide syntase gene polymorphysm interacts with environmental and dietary factors to influence endothelial function // Circulat. Res. – 2002. – 90. – P.1153 – 1158. 55. Lembo G., De Luca N., Battagli C. et al. A common variant of endothelial nitric oxide synthase (Glu298Asp) is an independent risk factor for carotid atherosclerosis // Stroke. – 2001. – 32, N3. – P.735 – 740. 56. Liu J., Garcia – Cardena G., Sessa W.C. Biosynthesis and palmitoylation of endothelial nitric oxide synthase: mutagenesis of palmitoylation sites, cysteines-15 and/ or -26, argues against depalmitoylation-induced translocation of the enzyme // Biochemistry. – 1995. – 34, N38. – P.12333 – 12340. 57. Liyou N., Simons L., Friedlander Y. et al. Coronary artery disease is not associated with the E298 —>D variant of the constitutive, endothelial nitric oxide synthase gene / / Clin. Genet. – 1998. – 54, N6. – P.528 – 529. 58. Loke K.E., Messina E.J., Shesely E.G. et al. Potential role of eNOS in the therapeutic control of myocardial oxygen consumption by ACE inhibitors and amlodipine // Cardiovasc. Res. – 2001. – 49, N1. – P.86 – 93. 59. Markus H.S., Ruigrok Y., Ali N., Powell J.F. Endothelial nitric oxide synthase exon 7 polymorphism, ischemic cerebrovascular disease, and carotid atheroma // Stroke. – 1998. – 29, N9. – P.1908 – 1911. 60. Matsushita H., Chang E., Glassford A.J. et al. eNOS activity is reduced in senescent human endothelial cells: preservation by hTERT immortalization // Circulat. Res. – 2001. – 89, N9. – P.793 – 798. 61. Michel J.B., Feron O., Sase K. Et al. Caveolin versus Calmodulin.Counterbalancing allosteric modulators of endothelial nitric oxide synthase // J. Biol. Chem. – 1997. – 272, N41. – P.25907 – 25912. 62. Michel J.B., Michel T. The role of palmitoyl-protein thioesterase in the palmitoylation of endothelial nitric oxide synthase // FEBS Lett. – 1997. – 405, N3. – P.356 – 362. 63. Michel T. Targeting and translocation of endothelial nitric oxide synthase // Braz. J. Med. Biol. Res. – 1999. – 32, N11. – P.1361 – 1366. 64. Miyamoto Y., Saito Y., Kajiyama N. et al. Endothelial nitric oxide synthase gene is positively associated with essential hypertension // Hypertension. – 1998. – 32, N1. – P.3 – 8. 65. Miyamoto Y., Saito Y., Nakayama M. et al. Replication protein A1 reduces transcription of the endothelial nitric oxide synthase gene containing a -786T —>C mutation associated with coronary spastic angina // Hum Mol. Genet. – 2000. – 9, N18. – P.2629 – 2637. Moibenko A.A., Brovkovich V.M., Kotsuruba A.I. et al. Nitric oxyde and myocardial ischemia // J. Mol. and Cell Cardiol. – 1999. – 31, N6. – A52. 67. Moibenko A.A., Yuzkiv M.Ya., Datsenko V.V. et al. Vascular mechanisms for compensation of the distur-bances related to acute myocardial infarction: the role of nitric oxide // J. Mol. and Cell Cardiol. – 2001. – 33, N6. – A.77. 68. Moncada S., Palmer R.M., Higgs E.A. Niric oxide: physiology, pathophysiology, an pharmacology // Pharmacol. Rev. – 1991. – 43. – P.109 – 142. 69. Naber C.K., Baumgart D., Altmann C. et al. eNOS 894T allele and coronary blood flow at rest and during adenosine-induced hyperemia // Amer. J. Physiol. Heart Circulat. Physiol. – 2001. – 281, N5. – P.1908 – 1912. 70. Nakagami H., Ikeda U., Maeda Y. et al. Coronary artery disease and endothelial nitric oxide synthase and angiotensin – converting enzyme gene polymorphisms // J. Thromb. Thrombolysis. – 1999. – 8, N3. – P.191 – 195. 71. Nakayama M., Yasue H., Yoshimura M. et al. T-786®C Mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm // Circulation. – 1999. – 99. – P.2864 – 2870. 72. Nakayama M., Yasue H., Yoshimura M. et al. T(-786) — > C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with myocardial infarction, especially without coronary organic stenosis // Amer. J. Cardiol. – 2000. – 86, N6. – P.628 – 634. 73. Nasreen S., Nabika T., Shibata H. et al. T-786C polymorphism in endothelial NO synthase gene affects cerebral circulation in smokers: possible geneenvironmental interaction // Arterioscler. Thromb. Vasc. Biol. – 2002. – 22, N4. – P.605 – 610. 74. Nassar B.A., Bevin L.D., Johnstone D.E. et al. Relationship of the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene and early-onset coronary artery disease // Amer. Heart J. – 2001. – 142, N4. – P.586 – 589. 75. Novoradovsky A., Brantly M.L., Waclawiw M.A. et al. Endothelial nitric oxide synthase as a potential susceptibility gene in the pathogenesis of emphysema in a1 – antitrypsin deficiency // Amer. J. Respir. Cell Mol. Biol. – 1999. – 20. – P.441 – 447. 76. Paradossi U., Colombo M.G., Andreassi M.G. et al. Evidence for association of a common variant of the endothelium nitric oxide synthase gene (Glu298 – Asp polymorphism) to the presence, extent and severity of coronary artery disease in the Italian population // VI International Learning Meeting (Bologna, Italy; May 30 – 31, June 1, 2002). – P.96. 77. Park J.E., Lee W.H., Hwang T.H. et al. Aging affects the association between endothelial nitric oxide synthase gene polymorphism and acute myocardial infarction in the Korean male population // Korean J. Intern. Med. – 2000. – 15, N1. – P.65 – 70. 78. Petit F., Jarrousse A.S., Dahlmann B. et al. Involvement of proteasomal subunits zeta and iota in RNA degradation // Biochem. J. – 1997. – 326, Pt 1. – P.93 – 98. 79. Philip I., Plantefeve G., Vuillaumier – Barrot S. et al. G894T polymorphism in the endothelial nitric oxide synthase gene is associated with an enhanced vascular responsiveness to phenylephrine // Circulation. – 1999. – 99, N24. – P.3096 – 3098. 80. Piacentini L., Karliner J.S. Altered gene expression during hypoxia and reoxygenation of the heart // Pharmacology and Theraputics. – 1999. – 83. – P.21 – 37. 81. Pouch M.N., Petit F., Buri J. et al. Identification and initial characterization of a specific proteasome (prosome) associated RNase activity // J. Biol. Chem. – 1995. – 270, N37. – P.22023 – 22028. 82. Pulkkinen A., Viitanen L., Kareinen A. et al. Intron 4 polymorphism of the endothelial nitric oxide synthase gene is associated with elevated blood pressure in type 2 diabetic patients with coronary heart disease // J. Mol. Med. – 2000. – 78, N7. – P.372 – 379. 83. Rakhit A., Maguire C.T., Wakimoto H. et al. In vivo electrophysiologic studies in endothelial nitric oxide synthase (eNOS)-deficient mice // J. Cardiovasc. Electrophysiol. – 2001. – 12, N11. – P.1295 – 1301. 84. Razani B., Engelman J.A., Wang X.B. et al. Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities // J. Biol. Chem. – 2001. – 276, N41. – P.38121 – 38138. 85. Sakai K., Hirooka Y., Matsuo I. et al. Overexpression of eNOS in NTS causes hypotension and bradycardia in vivo // Hypertension. – 2000. – 36, N6. – P.1023 – 1028. 86. Schneider M.P., Erdmann J., Delles C. et al. Functional gene testing of the Glu298Asp polymorphism of the endothelial NO synthase // J. Hypertens. – 2000. – 18, N12. – P.1767 – 1773. 87. Searles C.D., Miwa Y., Harrison D., Ramasamy S. Posttranscriptional regulation of endothelial nitric oxide synthase guring cell growth // Circulat. Res. – 1999. – 85. – P.588 – 595. 88. Shah V., Wiest R., Garcia-Cardena G. Et al. Hsp90 regulation of endothelial nitric oxide synthase contributes to vascular control in portal hypertension // Amer. J. Physiol. – 1999. – 277. – G463 – G468. 89. Shaul P.W. Regulation of endothelial nitric oxide synthase: location, location, location // Ann. Rev. Physiol. – 2002. – 64. – P.749 – 774. 90. Shaul P.W., Smart E.J., Robinson L.J. et al. Aculation targets endothelial nitric-oxide synthase to plasmalemmal caveole // J. Biol. Chem. – 1996. – 271, N11. – P.6518 – 6522. 91. Sheehy A.M., Burson M.A., Black S.M. Nitric oxide exposure inhibits endothelial NOS activity but not gene expression: a role for superoxide // Amer. J. Physiol. – 1998. – 274, N5, Pt 1. – P.833 – 841. 92. Shi Y., Baker J.E., Zhang C. et al. Chronic hypoxia increases endothelial nitric oxide syntase generation of nitric oxide by increasing heat shock protein 90 association and serine phosphorylation // Circulat. Res. – 2002. – 91. – P.300 – 306. 93. Shimasaki Y., Yasue H., Yoshimura M. et al. Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction // J. Amer. Coll. Cardiol. – 1998. – 31, N7. – P.1506 – 1510. 94. Shiojima I., Walsh K. Role of akt signaling in vascular homeostasis and angiogenesis // Circulat. Res. – 2002. – 90. – P.1243 – 1250. 95. Shoji M., Tsutaya S., Saito R. et al. Positive association of endothelial nitric oxide synthase gene polymorphism with hypertension in northern Japan // Life Sci. – 2000. – 66, N26. – P.2557 – 2562. 96. Shoji M., Yasujima M. Endothelial nitric oxide synthase gene and hypertension // Nippon Rinsho. – 2000. – 58, Suppl.1. – P.570 – 573. 97. Sigusch H.H., Surber R., Lehmann M.H. et al. Lack of association between 27-bp repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene and the risk of coronary artery disease // Scand. J. Clin. Lab. Invest. – 2000. – 60, N3. – P.229 – 235. 98. Sowa G., Liu J., Papapetropoulos A. et al. Trafficking of endothelial nitric – oxide synthase in living cells. Quantitative evidence supporting the role of palmitoylation as a kinetic trapping mechanism limiting membrane diffusion // J. Biol. Chem. – 1999. – 274, N32. – P.22524 – 22531. 99. Stangl K., Cascorbi I., Laule M. et al. High CA repeat numbers in intron 13 of the endothelial nitric oxide synthase gene and increased risk of coronary artery disease // Pharmacogenetics. – 2000. – 10, N2. – P.133 – 140. 100. Takaoka M., Okamoto H., Ito M. Et al. Antihypertensive effect of a proteasome inhibitor in DOCAsalt hypertensive rats // Life Sci. – 1998. – 63, N4 – PL65 – 70. 101. Tanus-Santos J.E., Desai M., Deak L.R. et al. Effects of endothelial nitric oxide synthase gene polymorphisms on platelet function, nitric oxide release, and interactions with estradiol // Pharmacogenetics. – 2002. – 12, N5. – P.407 – 413. 102. Tanus-Santos J.E., Desai M., Flockhart D.A. Effects of ethnicity on the distribution of clinically relevant endothelial nitric oxide variants // Pharmacogenetics. – 2001. – 11, N8. – P.719 – 725. 103. Tesauro M., Thompson W.C., Rogliani P. et al. Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298 // Proc. Natl. Acad. Sci. USA. – 2000. – 97, N6. – P.2832 – 2835. 104. Thom S.R., Bhopale V., Fisher D. et al. Stimulation of nitric oxide syntase in cerebral cortex due to elevated partial pressures of oxygen: an oxidative stress response // J. Neurobiol. – 2002. – 51, N2. – P.85 – 100. 105. Tsujita Y., Baba S., Yamauchi R. et al. Association analyses between genetic polymorphisms of endothelial nitric oxide synthase gene and hypertension in Japanese: The Suita Study // J. Hypertens. – 2001. – 19, N11. – P.1941 – 1948. 106. Wang C.L., Hsu L.A., Ko Y.S. et al. Lack of association between the Glu298Asp variant of the endothelial nitric oxide synthase gene and the risk of coronary artery disease among Taiwanese // J. Formos. Med. Assoc. – 2001. – 100, N11. – P.736 – 740. 107. Wang J., Dudley D., Wang X.L. Haplotype-specific effects on endothelial NO synthase promoter efficiency: modifiable by cigarette smoking // Arterioscler. Thromb. Vasc. Biol. – 2002. – 22, N5. – P.1 – 4. 108. Wang X., Abdel-Rahman A.A. Estrogen modulation of eNOS activity and its association with caveolin-3 and calmodulin in rat hearts // Amer. J. Physiol. Heart. Circulat. Physiol. – 2002. – 282, N6. – P.2309 – 2315. 109. Wang X.L. Cigarette smoking, DNA variants in endothelial nitric oxide synthase gene and vascular disease // Contrib. Nephrol. – 2000. – 130. – P.53 – 67. 110. Wang X.L., Sim A.S., Badenhop R.F. et al. A smokingdependent risk of coronary artery disease associated with a polymorphism of the endothelial nitric oxide synthase gene // Nat. Med. – 1996. – 2, N1. – P.41 – 45. 111. Wang X.L., Sim A.S., Wang M.X. et al. Genotype dependent and cigarette specific effects on endothelial nitric oxide synthase gene expression and enzyme activity // FEBS Lett. – 2000. – 471, N1. – P.45 – 50. 112. Yasujima M., Tsutaya S., Shoji M. Endothelial nitric oxide synthase gene polymorphism and hypertension / / Rinsho Byori. – 1998. – 46, N12. – P.1199 – 1204. 113. Ying W – Z., Xia H., Sanders P.W. Nitric oxyde synthase mutation in Dahl/Rapp rats decrease enzyme stability / / Circulat. Res. – 2001. – 89, N4. – P.317 – 322. 114. Yoon Y., Song J., Hong S.H., Kim J.Q. Plasma nitric oxide concentrations and nitric oxide synthase gene polymorphisms in coronary artery disease // Clin. Chem. – 2000. – 46, N10. – P.1626 – 1630. 115. Yoshimura M., Nakayama M., Shimasaki Y. et al. A T-786 —>C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene and coronary arterial vasomotility // Amer. J. Cardiol. – 2000. – 85, N6. – P.710 – 714. 116. Yoshimura M., Yasue H., Nakayama M. et al. A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese // Hum. Genet. – 1998. – 103, N1. – P.65 – 69. 117. Yoshimura M., Yasue H., Nakayama M. et al. Genetic risk factors for coronary artery spasm: significance of endothelial nitric oxide synthase gene T-786 —>C and missense Glu298Asp variants // J. Investig. Med. – 2000. – 48, N5. – P.367 – 374. 118. Zhuo J.L., Mendelsohn F.A., Ohishi M. Perindopril alters vascular angiotensin-converting enzyme, AT(1) receptor, and nitric oxide synthase expression in patients with coronary heart disease // Hypertension. – 2002. – 39, N2, Pt2. – P.634 – 638.

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