Na+/H+ exchanger-1: A link with atherogenesis?

Expert Opinion on Investigational Drugs

Volumn 19, Issue 12, 2010, Pages 1545-1556

  Sarigianni, Maria ^a,b   Tsapas, Apostolos ^a,c   Mikhailidis, Dimitri P ^b   Kaloyianni, Martha ^d   Koliakos, George ^a   Fliegel, Larry ^e   Paletas, Konstantinos ^a  

^a ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

^e UNIVERSITY OF ALBERTA   (Canada)

Author keywords

Atherosclerosis; Cariporide; Endothelial cells; Monocytes; Platelets; Smooth muscle cells; Sodium hydrogen antiporter

Indexed keywords

5 (N,N HEXAMETHYLENE)AMILORIDE; ADRENALIN; AMILORIDE; ANGIOTENSIN II; ARACHIDONIC ACID; CARIPORIDE; CD39 ANTIGEN; ENALAPRIL; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; ENDOTHELIN 1; ENIPORIDE; ESTRADIOL; INTERCELLULAR ADHESION MOLECULE 1; LEPTIN; LOSARTAN; MONOCYTE CHEMOTACTIC PROTEIN 1; N AMIDINO 1,4 DIMETHYL 1H INDOLE 2 CARBOXAMIDE; NIFEDIPINE; NITRIC OXIDE; PADGEM PROTEIN; PHOSPHATIDYLSERINE; PLACEBO; PROSTACYCLIN; SMALL INTERFERING RNA; SODIUM PROTON EXCHANGE PROTEIN 1; SYNAPSIN I; THROMBIN; UNINDEXED DRUG; VASCULAR CELL ADHESION MOLECULE 1; ZONIPORIDE;

ANION EXCHANGE; APOPTOSIS; ATHEROGENESIS; CELL ADHESION; CELL MIGRATION; CELL PROLIFERATION; DIABETES MELLITUS; DISEASE ASSOCIATION; DYSLIPIDEMIA; ENDOTHELIUM CELL; HUMAN; HYPERTENSION; INFLAMMATION; LOADING DRUG DOSE; MONOCYTE; NONHUMAN; OBESITY; OXIDATIVE STRESS; PH; REVIEW; RISK FACTOR; SMOKING; SMOOTH MUSCLE FIBER; THROMBOCYTE;

ANIMALS; ATHEROSCLEROSIS; CATION TRANSPORT PROTEINS; ENDOTHELIUM, VASCULAR; HUMANS; HYDROGEN-ION CONCENTRATION; HYPERTENSION; INFLAMMATION; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE; SODIUM-HYDROGEN ANTIPORTER;

EID: 78649522151     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.2010.532123     Document Type: Review

References (143)

1. Putney LK, Denker SP, Barber DL. The changing face of the Na+/H+ exchanger, NHE1: structure, regulation, and cellular actions. Annu Rev Pharmacol Toxicol 2002;42:527-52
2. Fliegel L. The Na+/H+ exchanger isoform 1. Int J Biochem Cell Biol 2005;37:33-7
3. Orlowski J, Grinstein S. Diversity of the mammalian sodium/proton exchanger SLC9 gene family. Pflugers Arch 2004;447:549-65
4. Lamon BD, Hajjar DP. Inflammation at the molecular interface of atherogenesis: an anthropological journey. Am J Pathol 2008;173:1253-64
5. Libby P, Ridker PM, Hansson GK. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol 2009;54:2129-38
6. Insull W Jr. The pathology of atherosclerosis: plaque development and plaque responses to medical treatment. Am J Med 2009;122:S3-14
7. Mentzer RM Jr, Bartels C, Bolli R, et al. Sodium-hydrogen exchange inhibition by cariporide to reduce the risk of ischemic cardiac events in patients undergoing coronary artery bypass grafting: results of the EXPEDITION study. Ann Thorac Surg 2008;85:1261-70
8. Teiwes J, Toto RD. Epithelial sodium channel inhibition in cardiovascular disease. A potential role for amiloride. Am J Hypertens 2007;20:109-17
9. Tardif JC, Mercier LA, Theroux P. Effect of inhibition of the Na+/H+ exchanger with cariporide on left ventricular function in acute coronary syndromes: results from the echocardiographic substudy of the GUARDIAN trial. Can J Cardiol 2004;20:317-22
10. Zeymer U, Suryapranata H, Monassier JP, et al. The Na(+)/H(+) exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction. Results of the evaluation of the safety and cardioprotective effects of eniporide in acute myocardial infarction (ESCAMI) trial. J Am Coll Cardiol 2001;38:1644-50
11. Marcus AJ, Broekman MJ, Drosopoulos JH, et al. Role of CD39 (NTPDase-1) in thromboregulation, cerebroprotection, and cardioprotection. Semin Thromb Hemost 2005;31:234-46
12. Yamamoto S, Matsui K, Itoh N, et al. The effect of an Na+/H+ exchange inhibitor, SM-20550, on ischemia/ reperfusion-induced endothelial dysfunction in isolated perfused rat hearts. Int J Tissue React 2001;23:1-7
13. Symons JD, Schaefer S. Na(+)/H(+) exchange subtype 1 inhibition reduces endothelial dysfunction in vessels from stunned myocardium. Am J Physiol Heart Circ Physiol 2001;281:H1575-82
14. Muraki S, Morris CD, Budde JM, et al. Blood cardioplegia supplementation with the sodium-hydrogen ion exchange inhibitor cariporide to attenuate infarct size and coronary artery endothelial dysfunction after severe regional ischemia in a canine model. J Thorac Cardiovasc Surg 2003;125:155-64
15. Besse S, Tanguy S, Boucher F, et al. Protection of endothelial-derived vasorelaxation with cariporide, a sodium-proton exchanger inhibitor, after prolonged hypoxia and hypoxia-reoxygenation: effect of age. Eur J Pharmacol 2006;531:187-93
16. Zatta AJ, Matherne GP, Headrick JP. Adenosine receptor-mediated coronary vascular protection in post-ischemic mouse heart. Life Sci 2006;78:2426-37
17. Gumina RJ, Moore J, Schelling P, et al. Na(+)/H(+) exchange inhibition prevents endothelial dysfunction after I/R injury. Am J Physiol Heart Circ Physiol 2001;281:H1260-6
18. Kitazono T, Kamouchi M, Ago T, et al. Role of Na(+)/H(+) exchanger in dilator responses of rat basilar artery in vivo. Brain Res 2001;906:101-6
19. Alnaeb ME, Thompson CS, Seifalian AM, et al. Regional differences in the expression of nitric oxide synthase and specific receptors in the vascular tissues of control and diabetic rabbits: a pilot study. In Vivo 2007;21:1069-74
20. Aldakkak M, Stowe DF, Heisner JS, et al. Enhanced Na+/H+ exchange during ischemia and reperfusion impairs mitochondrial bioenergetics and myocardial function. J Cardiovasc Pharmacol 2008;52:236-44
21. Konstantinidis D, Paletas K, Koliakos G, et al. Signaling components involved in leptin-induced amplification of the atherosclerosis-related properties of human monocytes. J Vasc Res 2009;46:199-208
22. Xue J, Zhou D, Yao H, et al. Novel functional interaction between Na+/H+ exchanger 1 and tyrosine phosphatase SHP-2. Am J Physiol Regul Integr Comp Physiol 2007;292:R2406-16
23. Wang S, Peng Q, Zhang J, et al. Na+/H+ exchanger is required for hyperglycaemia-induced endothelial dysfunction via calcium-dependent calpain. Cardiovasc Res 2008;80:255-62
24. Masereel B, Pochet L, Laeckmann D. An overview of inhibitors of Na(+)/H(+) exchanger. Eur J Med Chem 2003;38:547-54
25. Vial G, Dubouchaud H, Couturier K, et al. Na+/H+ exchange inhibition with cariporide prevents alterations of coronary endothelial function in streptozotocin-induced diabetes. Mol Cell Biochem 2008;310:93-102
26. Ando K, Takahashi K, Ono A, et al. Possible role of sodium-hydrogen antiport in acetylcholine-induced relaxation of rat aorta. Biochem Biophys Res Commun 1991;177:407-13
27. Shankar R, de la Motte CA, DiCorleto PE. Thrombin stimulates PDGF production and monocyte adhesion through distinct intracellular pathways in human endothelial cells. Am J Physiol 1992;262:C199-206
28. Buerke U, Pruefer D, Carter JM, et al. Sodium/hydrogen exchange inhibition with cariporide reduces leukocyte adhesion via P-selectin suppression during inflammation. Br J Pharmacol 2008;153:1678-85
29. Wang SX, Sun XY, Zhang XH, et al. Cariporide inhibits high glucose-mediated adhesion of monocyte-endothelial cell and expression of intercellular adhesion molecule-1. Life Sci 2006;79:1399-404
30. Nemeth ZH, Deitch EA, Lu Q, et al. NHE blockade inhibits chemokine production and NF-kappab activation in immunostimulated endothelial cells. Am J Physiol Cell Physiol 2002;283:C396-403
31. Huck V, Niemeyer A, Goerge T, et al. Delay of acute intracellular pH recovery after acidosis decreases endothelial cell activation. J Cell Physiol 2007;211:399-409
32. Park KS, Poburko D, Wollheim CB, et al. Amiloride derivatives induce apoptosis by depleting ER Ca(2+) stores in vascular endothelial cells. Br J Pharmacol 2009;156:1296-304
33. Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 2006;354:610-21
34. Viola A, Luster AD. Chemokines and their receptors: drug targets in immunity and inflammation. Annu Rev Pharmacol Toxicol 2008;48:171-97
35. Rao GN, de Roux N, Sardet C, et al. Na+/H+ antiporter gene expression during monocytic differentiation of HL60 cells. J Biol Chem 1991;266:13485-8
36. Lei L, Dou L, Yan L, et al. Effect of NHE1 on stem cell differentiation into cardiomyocytes. Sheng Wu Gong Cheng Xue Bao 2008;24:1790-5
37. Li X, Karki P, Lei L, et al. Na+/H+ exchanger isoform 1 facilitates cardiomyocyte embryonic stem cell differentiation. Am J Physiol Heart Circ Physiol 2009;296:H159-70
38. Koliakos G, Befani C, Paletas K, et al. Effect of endothelin on sodium/hydrogen exchanger activity of human monocytes and atherosclerosis- related functions. Ann N Y Acad Sci 2007;1095:274-91
39. Kaloyianni M, Zolota Z, Paletas K, et al. Cariporide counteracts atherosclerosis-related functions in monocytes from obese and normal individuals. Obes Res 2005;13:1588-95
40. Koliakos G, Zolota Z, Paletas K, et al. High glucose concentrations stimulate human monocyte sodium/hydrogen exchanger activity and modulate atherosclerosis-related functions. Pflugers Arch 2004;449:298-306
41. Sarigianni M, Bekiari E, Tsapas A, et al. Effect of epinephrine and insulin resistance on human monocytes obtained from lean and obese healthy subjects: a pilot study. Angiology 2010; In press
42. Sarigianni M, Bekiari E, Tsapas A, et al. Effect of leptin and insulin resistance on properties of human monocytes in lean and obese healthy subjects. Angiology 2010; In press
43. Li Z, Song T, Liu GZ, et al. Inhibitory effects of cariporide on LPC-induced expression of ICAM-1 and adhesion of monocytes to smooth muscle cells in vitro. Acta Pharmacol Sin 2006;27:1326-32
44. Schwartz SM, Virmani R, Rosenfeld ME. The good smooth muscle cells in atherosclerosis. Curr Atheroscler Rep 2000;2:422-9
45. Bentzon JF, Weile C, Sondergaard CS, et al. Smooth muscle cells in atherosclerosis originate from the local vessel wall and not circulating progenitor cells in apoE knockout mice. Arterioscler Thromb Vasc Biol 2006;26:2696-702
46. Doran AC, Meller N, McNamara CA. Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arterioscler Thromb Vasc Biol 2008;28:812-19
47. Boedtkjer E, Praetorius J, Aalkjaer C. Nbcn1 (SLC4A7) mediates the Na+-dependent bicarbonate transport important for regulation of intracellular pH in mouse vascular smooth muscle cells. Circ Res 2006;98:515-23
48. Apkon M, Weed RA, Boron WF. Motor responses of cultured rat cerebral vascular smooth muscle cells to intra- and extracellular pH changes. Am J Physiol 1997;273:H434-45
49. Aalkjaer C, Mulvany MJ. Effect of changes in intracellular pH on the contractility of rat resistance vessels. Prog Biochem Pharmacol 1988;23:150-8
50. Incerpi S, D'Arezzo S, Marino M, et al. Short-term activation by low 17beta-estradiol concentrations of the Na+/H+ exchanger in rat aortic smooth muscle cells: Physiopathological implications. Endocrinology 2003;144:4315-24
51. Berk BC, Vallega G, Muslin AJ, et al. Spontaneously hypertensive rat vascular smooth muscle cells in culture exhibit increased growth and Na+/H+ exchange. J Clin Invest 1989;83:822-9
52. Bkaily G, Nader M, Avedanian L, et al. G-protein-coupled receptors, channels, and Na+/H+ exchanger in nuclear membranes of heart, hepatic, vascular endothelial, and smooth muscle cells. Can J Physiol Pharmacol 2006;84:431-41
53. Wu D, Doods H, Stassen JM. Inhibition of human pulmonary artery smooth muscle cell proliferation and migration by sabiporide, a new specific NHE-1 inhibitor. J Cardiovasc Pharmacol 2006;48:34-40
54. Takewaki S, Kuro-o M, Hiroi Y, et al. Activation of Na(+)-H+ antiporter (NHE-1) gene expression during growth, hypertrophy and proliferation of the rabbit cardiovascular system. J Mol Cell Cardiol 1995;27:729-42
55. Chen YX, O'Brien ER. Ethyl isopropyl amiloride inhibits smooth muscle cell proliferation and migration by inducing apoptosis and antagonizing urokinase plasminogen activator activity. Can J Physiol Pharmacol 2003;81:730-9
56. Rich IN, Worthington-White D, Garden OA, et al. Apoptosis of leukemic cells accompanies reduction in intracellular pH after targeted inhibition of the Na(+)/H(+) exchanger. Blood 2000;95:1427-34
57. Schneider D, Gerhardt E, Bock J, et al. Intracellular acidification by inhibition of the Na+/H+-exchanger leads to caspase-independent death of cerebellar granule neurons resembling paraptosis. Cell Death Differ 2004;11:760-70
58. Langer HF, Gawaz M. Platelet-vessel wall interactions in atherosclerotic disease. Thromb Haemost 2008;99:480-6
59. Tsiara S, Elisaf M, Jagroop IA, et al. Platelets as predictors of vascular risk: is there a practical index of platelet activity? Clin Appl Thromb Hemost 2003;9:177-90
60. Siffert W. Regulation of platelet function by sodium-hydrogen exchange. Cardiovasc Res 1995;29:160-6
61. Xu WT, Jin N, Xu J, et al. Design, synthesis and biological evaluation of novel substituted benzoylguanidine derivatives as potent Na+/H+ exchanger inhibitors. Bioorg Med Chem Lett 2009;19:3283-7
62. Jagroop IA, Clatworthy I, Lewin J, et al. Shape change in human platelets: measurement with a channelyzer and visualisation by electron microscopy. Platelets 2000;11:28-32
63. Flaumenhaft R. Molecular basis of platelet granule secretion. Arterioscler Thromb Vasc Biol 2003;23:1152-60
64. Stelmach H, Rusak T, Tomasiak M. The involvement of the Na(+)/H(+) exchanger in the formation of microvesicles by porcine platelets. Haematologia (Budap) 2002;32:239-52
65. Tomasiak M, Ciborowski M, Stelmach H. The role of Na+/H+ exchanger in serotonin secretion from porcine blood platelets. Acta Biochim Pol 2005;52:811-22
66. Nofer JR, Tepel M, Kehrel B, et al. Low-density lipoproteins inhibit the Na+/H+ antiport in human platelets. A novel mechanism enhancing platelet activity in hypercholesterolemia. Circulation 1997;95:1370-7
67. Barradas MA, Gill DS, Fonseca VA, et al. Intraplatelet serotonin in patients with diabetes mellitus and peripheral vascular disease. Eur J Clin Invest 1988;18:399-404
68. Barradas MA, Mikhailidis DP. Serotonin, histamine and platelets in vascular disease with special reference to peripheral vascular disease. Braz J Med Biol Res 1992;25:1063-76
69. Bucki R, Pastore JJ, Giraud F, et al. Involvement of the Na+/H+ exchanger in membrane phosphatidylserine exposure during human platelet activation. Biochim Biophys Acta 2006;1761:195-204
70. Tomasiak M, Stelmach H, Rusak T, et al. Vasopressin acts on platelets to generate procoagulant activity. Blood Coagul Fibrinolysis 2008;19:615-24
71. Lee KS, Jin YR, Lee JJ, et al. Anti-platelet activity of KR-32560, a novel sodium/hydrogen exchanger-1 inhibitor. Pharmacol Res 2006;53:265-70
72. Tomasiak MM, Stelmach H, Bodzenta-Lukaszyk A, et al. Involvement of Na+/H+ exchanger in desmopressin-induced platelet procoagulant response. Acta Biochim Pol 2004;51:773-88
73. Klinkhardt U, Kuczka K, Harder S. Effects of the NHE-1 inhibitor cariporide alone or together with the P2Y12 antagonist AR-C 69331 mx on CD62P expression and formation of platelet-leukocyte aggregates. Thromb Res 2003;111:251-7
74. Delva P, Pastori C, Provoli E, et al. Erythrocyte Na(+)-H(+) exchange activity in essential hypertensive and obese patients: Role of excess body weight. J Hypertens 1993;11:823-30
75. Sarigianni M, Bekiari E, Tsapas A, et al. Effect of glucose and insulin on oxidized low density lipoprotein phagocytosis by human monocytes: a pilot study. Angiology 2010; In press
76. Paraskevas KI, Liapis CD, Mikhailidis DP. Leptin: a promising therapeutic target with pleiotropic action besides body weight regulation. Curr Drug Targets 2006;7:761-71
77. Ravussin E, Tataranni PA. The role of altered sympathetic nervous system activity in the pathogenesis of obesity. Proc Nutr Soc 1996;55:793-802
78. Grassi G, Quarti-Trevano F, Seravalle G, et al. Differential sympathetic activation in muscle and skin neural districts in the metabolic syndrome. Metabolism 2009;58:1446-51
79. Alvarez GE, Beske SD, Ballard TP, et al. Sympathetic neural activation in visceral obesity. Circulation 2002;106:2533-6
80. Sauvage M, Maziere P, Fathallah H, et al. Insulin stimulates NHE1 activity by sequential activation of phosphatidylinositol 3-kinase and protein kinase C zeta in human erythrocytes. Eur J Biochem 2000;267:955-62
81. Kaloyianni M, Bourikas D, Koliakos G. The effect of insulin on Na+/H+ antiport activity of obese and normal subjects erythrocytes. Cell Physiol Biochem 2001;11:253-8
82. Sarigianni M, Tsapas A, Mikhailidis DP, et al. Involvement of signaling molecules on Na+/H+ exchanger-1 activity in human monocytes. The open Cardiovasc Med J 2010:In press
83. Konstantinou-Tegou A, Kaloyianni M, Bourikas D, et al. The effect of leptin on Na(+)-H(+) antiport (NHE 1) activity of obese and normal subjects erythrocytes. Mol Cell Endocrinol 2001;183:11-8
84. Bourikas D, Kaloyianni M, Bougoulia M, et al. Modulation of the Na(+)-H(+) antiport activity by adrenaline on erythrocytes from normal and obese individuals. Mol Cell Endocrinol 2003;205:141-50
85. Kaloyianni M, Tsagias N, Liakos P, et al. Stimulation of Na+/H+ antiport and pyruvate kinase activities by high glucose concentration in human erythrocytes. Mol Cells 2004;17:415-21
86. Wang SX, Xiong XM, Song T, et al. Protective effects of cariporide on endothelial dysfunction induced by high glucose. Acta Pharmacol Sin 2005;26:329-33
87. Shuang-Xi W, Li-Ying L, Hu M, et al. Na+/H+exchanger inhibitor prevented endothelial dysfunction induced by high glucose. J Cardiovasc Pharmacol 2005;45:586-90
88. Russell JC, Proctor SD, Kelly SE, et al. Insulin-sensitizing and cardiovascular effects of the sodium-hydrogen exchange inhibitor, cariporide, in the JCR: LA-cp rat and db/db mouse. J Cardiovasc Pharmacol 2005;46:746-53
89. Pikilidou MI, Lasaridis AN, Sarafidis PA, et al. Insulin sensitivity increase after calcium supplementation and change in intraplatelet calcium and sodium-hydrogen exchange in hypertensive patients with type 2 diabetes. Diabet Med 2009;26:211-19
90. Fujioka Y, Masai M, Tsuboi S, et al. Troglitazone reduces activity of the Na+/H+ exchanger in fructose-fed borderline hypertensive rats. Hypertens Res 2003;26:111-16
91. Boedtkjer E, Aalkjaer C. Insulin inhibits Na+/H+ exchange in vascular smooth muscle and endothelial cells in situ: involvement of H2O2 and tyrosine phosphatase SHP-2. Am J Physiol Heart Circ Physiol 2009;296:H247-55
92. Le Prigent K, Lagadic-Gossmann D, Feuvray D. Modulation by pH0 and intracellular Ca2+ of Na(+)-H+ exchange in diabetic rat isolated ventricular myocytes. Circ Res 1997;80:253-60
93. Feuvray D. Intracellular pH control mechanisms in the diabetic myocardium. Diabetes Res Clin Pract 1996;31(Suppl):S87-92
94. Vaughan-Jones RD, Swietach P. Pushing and pulling the cardiac sodium/hydrogen exchanger. Circ Res 2008;103:773-5
95. Orlov SN, Adragna NC, Adarichev VA, et al. Genetic and biochemical determinants of abnormal monovalent ion transport in primary hypertension. Am J Physiol 1999;276:C511-36
96. Lifton RP, Hunt SC, Williams RR, et al. Exclusion of the Na(+)-H(+) antiporter as a candidate gene in human essential hypertension. Hypertension 1991;17:8-14
97. Bobulescu IA, Di Sole F, Moe OW. Na+/H++ exchangers: physiology and link to hypertension and organ ischemia. Curr Opin Nephrol Hypertens 2005;14:485-94
98. Frolich O, Karmazyn M. The Na-H exchanger revisited: an update on Na-H exchange regulation and the role of the exchanger in hypertension and cardiac function in health and disease. Cardiovasc Res 1997;36:138-48
99. Xiang M, Feng M, Muend S, et al. A human Na+/H+ antiporter sharing evolutionary origins with bacterial NHaA may be a candidate gene for essential hypertension. Proc Natl Acad Sci USA 2007;104:18677-81
100. Chau WH, Lee WH, Lau WH, et al. Role of Na+/H+ exchanger in acetylcholine-mediated pulmonary artery contraction of spontaneously hypertensive rats. Eur J Pharmacol 2003;464:177-87
101. Ghigo D, Alessio P, Burzacca S, et al. Na+/H+ antiporter activity in peripheral blood lymphocytes of obese and type 2 diabetic patients is increased only in the presence of arterial hypertension. Eur J Clin Invest 1994;24:166-72
102. Zerbini G, Maestroni A, Breviario D, et al. Alternative splicing of NHE-1 mediates Na-Li countertransport and associates with activity rate. Diabetes 2003;52:1511-18
103. Dworschak M, d'Uscio LV, Breukelmann D, et al. Increased tolerance to hypoxic metabolic inhibition and reoxygenation of cardiomyocytes from apolipoprotein E-deficient mice. Am J Physiol Heart Circ Physiol 2005;289:H160-7
104. Zicha J, Kunes J, David-Dufilho M, et al. Cell calcium handling and intracellular pH regulation in hereditary hypertriglyceridemic rats: reduced platelet response to thrombin stimulation. Life Sci 1996;59:803-13
105. Nofer JR, Noll C, Feuerborn R, et al. Low density lipoproteins inhibit the Na+/H+ antiport in human platelets via activation of p38MAP kinase. Biochem Biophys Res Commun 2006;340:751-7
106. Nofer JR, Tepel M, Kehrel B, et al. High density lipoproteins enhance the Na+/H+ antiport in human platelets. Thromb Haemost 1996;75:635-41
107. Navab M, Anantharamaiah GM, Reddy ST, et al. HDL as a biomarker, potential therapeutic target, and therapy. Diabetes 2009;58:2711-17
108. Tekpli X, Huc L, Lacroix J, et al. Regulation of Na+/H+ exchanger 1 allosteric balance by its localization in cholesterol- and caveolin-rich membrane microdomains. J Cell Physiol 2008;216:207-20
109. Konstantinidis D, Paletas K, Koliakos G, et al. The ambiguous role of the Na+/H+ exchanger isoform 1 (NHE1) in leptin-induced oxidative stress in human monocytes. Cell Stress Chaperones 2009;14:591-601
110. Babizhayev MA, Yegorov YE. Smoking and health: association between telomere length and factors impacting on human disease, quality of life and life span in a large population-based cohort under the effect of smoking duration. Fundam Clin Pharmacol 2010; In press
111. Rungwerth K, Schindler U, Gerl M, et al. Inhibition of Na+/H+ exchange by cariporide reduces inflammation and heart failure in rabbits with myocardial infarction. Br J Pharmacol 2004;142:1147-54
112. Sweatt JD, Johnson SL, Cragoe EJ, et al. Inhibitors of Na+/H+ exchange block stimulus-provoked arachidonic acid release in human platelets. Selective effects on platelet activation by epinephrine, ADP, and lower concentrations of thrombin. J Biol Chem 1985;260:12910-19
113. Kamachi F, Ban HS, Hirasawa N, et al. Inhibition of lipopolysaccharide- induced prostaglandin E2 production and inflammation by the Na+/H+ exchanger inhibitors. J Pharmacol Exp Ther 2007;321:345-52
114. Khan I, Oriowo MA, Anim JT. Amelioration of experimental colitis by Na-H exchanger-1 inhibitor amiloride is associated with reversal of IL-1ss and ERK mitogen-activated protein kinase. Scand J Gastroenterol 2005;40:578-85
115. Ridker PM, Morrow DA, Rose LM, et al. Relative efficacy of atorvastatin 80 mg and pravastatin 40 mg in achieving the dual goals of low-density lipoprotein cholesterol ≤ 70 mg/dl and C-reactive protein ≤ 2 mg/l: An analysis of the PROVE-IT TIMI-22 trial J Am Coll Cardiol 2005 45 1644-8
116. Akram S, Teong HF, Fliegel L, et al. Reactive oxygen species-mediated regulation of the Na+/H+ exchanger 1 gene expression connects intracellular redox status with cells' sensitivity to death triggers. Cell Death Differ 2006;13:628-41
117. Harrison D, Griendling KK, Landmesser U, et al. Role of oxidative stress in atherosclerosis. Am J Cardiol 2003;91:7A-11A
118. Bonomini F, Tengattini S, Fabiano A, et al. Atherosclerosis and oxidative stress. Histol Histopathol 2008;23:381-90
119. Imahashi K, Mraiche F, Steenbergen C, et al. Overexpression of the Na+/H+ exchanger and ischemia-reperfusion injury in the myocardium. Am J Physiol Heart Circ Physiol 2007;292:H2237-47
120. Fliegel L. Regulation of the Na(+)/H(+) exchanger in the healthy and diseased myocardium. Expert Opin Ther Targets 2009;13:55-68
121. Karmazyn M, Sawyer M, Fliegel L. The Na(+)/H(+) exchanger: a target for cardiac therapeutic intervention. Curr Drug Targets Cardiovasc Haematol Disord 2005;5:323-35
122. Wang P, Zaragoza C, Holman W. Sodium-hydrogen exchange inhibition and beta-blockade additively decrease infarct size. Ann Thorac Surg 2007;83:1121-7
123. Theroux P, Chaitman BR, Danchin N, et al. Inhibition of the sodium-hydrogen exchanger with cariporide to prevent myocardial infarction in high-risk ischemic situations. Main results of the GUARDIAN trial. Guard during ischemia against necrosis (GUARDIAN) investigators. Circulation 2000;102:3032-8
124. Boyce SW, Bartels C, Bolli R, et al. Impact of sodium-hydrogen exchange inhibition by cariporide on death or myocardial infarction in high-risk CABG surgery patients: results of the CABG surgery cohort of the GUARDIAN study. J Thorac Cardiovasc Surg 2003;126:420-7
125. Chaitman BR. A review of the guardian trial results: clinical implications and the significance of elevated perioperative ck-mb on 6-month survival. J Card Surg 2003;18(Suppl 1):13-20
126. Fleisher LA, Newman MF, St Aubin LB, et al. Efficacy of zoniporide, an Na/H exchange ion inhibitor, for reducing perioperative cardiovascular events in vascular surgery patients. J Cardiothorac Vasc Anesth 2005;19:570-6
127. Bhattaram VA, Nagaraja NV, Peters T, et al. Population pharmacokinetics of eniporide and its metabolite in healthy subjects and patients with acute myocardial infarction. J Clin Pharmacol 2005;45:631-9
128. Zhang R, Dong J, Xu YG, et al. Synthesis and bioactivity of substituted indan-1-ylideneaminoguanidine derivatives. Eur J Med Chem 2009;44:3771-6
129. Zhang R, Lei L, Xu YG, et al. Benzimidazol-2-yl or benzimidazol-2- ylthiomethyl benzoylguanidines as novel na+/h+ exchanger inhibitors, synthesis and protection against ischemic-reperfusion injury. Bioorg Med Chem Lett 2007;17:2430-3
130. Mao D, Xu Y, Hu X, et al. Synthesis and Na(+)/H(+) exchanger-1 inhibitory activity of substituted (quinolinecarbonyl) guanidine derivatives. Chem Biodivers 2009;6:1727-36
131. Kusumoto K, Igata H, Abe A, et al. In vitro and in vivo pharmacology of a structurally novel Na+/H+ exchange inhibitor, T-162559. Br J Pharmacol 2002;135:1995-2003
132. Fukumoto S, Imamiya E, Kusumoto K, et al. Novel, non-acylguanidine-type Na (+)/H(+) exchanger inhibitors: synthesis and pharmacology of 5-tetrahydroquinolinylidene aminoguanidine derivatives. J Med Chem 2002;45:3009-21
133. Yamamoto S, Matsui K, Sasabe M, et al. Effect of an orally active Na+/H+ exchange inhibitor, SMP-300, on experimental angina and myocardial infarction models in rats. J Cardiovasc Pharmacol 2002;39:234-41
134. Chesler M. Regulation and modulation of pH in the brain. Physiol Rev 2003;83:1183-221
135. Alvarez BV, Ennis IL, De Hurtado MC, et al. Effects of antihypertensive therapy on cardiac sodium/hydrogen ion exchanger activity and hypertrophy in spontaneously hypertensive rats. Can J Cardiol 2002;18:667-72
136. Falkner B, Canessa M, Anzalone D. Effect of angiotensin converting enzyme inhibitor (lisinopril) on insulin sensitivity and sodium transport in mild hypertension. Am J Hypertens 1995;8:454-60
137. Fortuno A, Tisaire J, Lopez R, et al. Angiotensin converting enzyme inhibition corrects Na+/H+ exchanger overactivity in essential hypertension. Am J Hypertens 1997;10:84-93
138. Ennis IL, Alvarez BV, Camilion de Hurtado MC, et al. Enalapril induces regression of cardiac hypertrophy and normalization of pHi regulatory mechanisms. Hypertension 1998;31:961-7
139. Sandmann S, Yu M, Kaschina E, et al. Differential effects of angiotensin AT1 and AT2 receptors on the expression, translation and function of the Na+/H+ exchanger and Na+-HCO3- symporter in the rat heart after myocardial infarction. J Am Coll Cardiol 2001;37:2154-65
140. Khan I, Al-Qattan KK, Alnaqeeb MA, et al. Altered expression of Na(+)/H(+) exchanger isoforms 1 and 3 in clipped and unclipped kidneys of a 2-kidney-1-clip Goldblatt model of hypertension. Nephron 2002;92:346-55
141. Lijnen P, Arabidze CG, Petrov V. Effect of angiotensin-converting enzyme inhibition on Na(+)/H(+)-exchange and Ca(2+)-efflux in human erythrocytes. Methods Find Exp Clin Pharmacol 1997;19:125-8
142. Syme PD, Brunotte F, Green Y, et al. The effect of beta 2-adrenoceptor stimulation and blockade of l-type calcium channels on in vivo Na+/H+ antiporter activity in rat skeletal muscle. Biochim Biophys Acta 1991;1093:234-40
143. Perez NG, Piaggio MR, Ennis IL, et al. Phosphodiesterase 5a inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction. Hypertension 2007;49:1095-103