Role of connexins in microvascular dysfunction during inflammation

Canadian Journal of Physiology and Pharmacology

Volumn 89, Issue 1, 2011, Pages 1-12

  Tyml, Karel ^a,b  

^a UNIVERSITY OF WESTERN ONTARIO   (Canada)

^b LAWSON HEALTH RESEARCH INSTITUTE   (Canada)

Author keywords

Connexins; Gap junctions; Lipopolysaccharide; Microcirculation; Nitric oxide; Oxidants; Sepsis

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 1H 1,2,4 OXADIAZOLO[4,3 A]QUINOXALIN 1 ONE; 2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 4 (4 FLUOROPHENYL) 2 (4 HYDROXYPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; 4 AMINO 7 TERT BUTYL 5 (4 CHLOROPHENYL)PYRAZOLO[3,4 D]PYRIMIDINE; 6-22 AMIDE; 8 BROMO CYCLIC AMP; ANTHRA[1,9 CD]PYRAZOL 6(2H) ONE; ASCORBIC ACID; BISINDOLYLMALEIMIDE; BRYOSTATIN 2; CONNEXIN 37; CONNEXIN 40; CONNEXIN 43; CYCLIC AMP DEPENDENT PROTEIN KINASE INHIBITOR; CYCLOHEXIMIDE; GAP JUNCTION PROTEIN; GELDANAMYCIN; LAVENDUSTIN C; LIPOPOLYSACCHARIDE; MANGANESE TETRAKIS( 4 BENZOIC ACID)PORPHYRIN CHLORIDE; MITOGEN ACTIVATED PROTEIN KINASE P38 INHIBITOR; N(G) NITROARGININE METHYL ESTER; NITRIC OXIDE; PORPHYRIN DERIVATIVE; PROTEIN TYROSINE KINASE INHIBITOR; SERINE; TYROSINE; TYRPHOSTIN A48; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTERIOLE; ATTENUATION; CAPILLARY; CELL CULTURE; CELL HYPOXIA; CELL MEMBRANE DEPOLARIZATION; CROSS COUPLING REACTION; DRUG MECHANISM; ELECTRIC CONDUCTIVITY; HYPERPOLARIZATION; IN VITRO STUDY; IN VIVO STUDY; MICROVASCULAR ENDOTHELIAL CELL; MICROVASCULATURE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS; REOXYGENATION; REVIEW; SEPSIS; SIGNAL TRANSDUCTION; SYSTEMIC INFLAMMATORY RESPONSE SYNDROME; SYSTEMIC VASCULAR RESISTANCE; VASCULAR DISEASE; VASOCONSTRICTION; VASODILATATION;

ANIMALS; ARTERIOLES; ARTERITIS; CONNEXINS; ENDOTHELIUM, VASCULAR; HUMANS; MICROVESSELS; SEPSIS; VASOCONSTRICTION;

EID: 78650583415     PISSN: 00084212     EISSN: 12057541     Source Type: Journal    
DOI: 10.1139/Y10-099     Document Type: Review

References (76)

1. Armour, J., Tyml, K., Lidington, D., and Wilson, J.X. 2001. Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat. J. Appl. Physiol. 90(3): 795-803. PMID: 11181585.
2. Baker, C.H., and Sutton, E.T. 1993. Arteriolar endothelium-dependent vasodilation occurs during endotoxin shock. Am. J. Physiol. 264(4 Pt 2): H1118-H1123. PMID:8476088.
3. Bari, F., Errico, R.A., Louis, T.M., and Busija, D.W. 1996. Differential effects of short-term hypoxia and hypercapnia on Nmethyl-D-aspartate-induced cerebral vasodilatation in piglets. Stroke, 27(9): 1634-1639, discussion 1639-1640. PMID: 8784141.
4. Blaise, G.A., Gauvin, D., Gangal, M., and Authier, S. 2005. Nitric oxide, cell signaling and cell death. Toxicology, 208(2): 177-192. doi:10.1016/j.tox.2004.11.032. PMID:15691583.
5. Bolon, M.L., Ouellette, Y., Li, F., and Tyml, K. 2005. Abrupt reoxygenation following hypoxia reduces electrical coupling between endothelial cells of wild-type but not connexin40 null mice in oxidantand PKA-dependent manner. FASEB J. 19(12): 1725-1727. PMID:16037099.
6. Bolon, M.L., Kidder, G.M., Simon, A.M., and Tyml, K. 2007. Lipopolysaccharide reduces electrical coupling in microvascular endothelial cells by targeting connexin40 in a tyrosine-, ERK1/ 2-, PKA-, and PKC-dependent manner. J. Cell. Physiol. 211(1): 159-166. doi:10.1002/jcp.20928. PMID:17149706.
7. Bolon, M.L., Peng, T., Kidder, G.M., and Tyml, K. 2008. Lipopolysaccharide plus hypoxia and reoxygenation synergistically reduce electrical coupling between microvascular endothelial cells by dephosphorylating connexin40. J. Cell. Physiol. 217(2): 350-359. doi:10.1002/jcp.21505. PMID:18521823.
8. Bone, R.C. 1991. Gram-negative sepsis. Background, clinical features, and intervention. Chest, 100(3): 802-808. doi:10.1378/ chest.100.3.802. PMID:1889276.
9. Brisset, A.C., Isakson, B.E., and Kwak, B.R. 2009. Connexins in vascular physiology and pathology. Antioxid. Redox Signal. 11(2): 267-282. doi:10.1089/ars.2008.2115. PMID:18834327.
10. Cronier, L., Crespin, S., Strale, P.O., Defamie, N., and Mesnil, M. 2009. Gap junctions and cancer: new functions for an old story. Antioxid. Redox Signal. 11(2): 323-338. doi:10.1089/ars.2008. 2153. PMID:18834328.
11. de Wit, C., and Griffith, T.M. 2010. Connexins and gap junctions in the EDHF phenomenon and conducted vasomotor responses. Pflugers Arch. 459(6): 897-914. doi:10.1007/s00424-010-0830-4. PMID:20379740.
12. de Wit, C., Roos, F., Bolz, S.S., Kirchhoff, S., Kruger, O., Willecke, K., and Pohl, U. 2000. Impaired conduction of vasodi-lation along arterioles in connexin40-deficient mice. Circ. Res. 86(6): 649-655. PMID:10747000.
13. DeFily, D.V. 1998. Control of microvascular resistance in physiological conditions and reperfusion. J. Mol. Cell. Cardiol. 30(12): 2547-2554. doi:10.1006/jmcc.1998.0826. PMID:9990526.
14. Dhein, S. 2004. Pharmacology of gap junctions in the cardiovascular system. Cardiovasc. Res. 62(2): 287-298. doi:10.1016/j.cardiores.2004.01.019. PMID:15094349.
15. Emerson, G.G., and Segal, S.S. 2001. Electrical activation of endothelium evokes vasodilation and hyperpolarization along hamster feed arteries. Am. J. Physiol. Heart Circ. Physiol. 280(1): H160-H167. PMID:11123230.
16. Figueroa, X.F., Paul, D.L., Simon, A.M., Goodenough, D.A., Day, K.H., Damon, D.N., and Duling, B.R. 2003. Central role of connexin40 in the propagation of electrically activated vasodilation in mouse cremasteric arterioles in vivo. Circ. Res. 92(7): 793-800. doi:10.1161/01.RES.0000065918.90271.9A. PMID: 12637364.
17. Gabriels, J.E., and Paul, D.L. 1998. Connexin43 is highly localized to sites of disturbed flow in rat aortic endothelium but connexin37 and connexin40 are more uniformly distributed. Circ. Res. 83(6): 636-643. PMID:9742059.
18. Gocan, N.C., Scott, J.A., and Tyml, K. 2000. Nitric oxide produced via neuronal NOS may impair vasodilatation in septic rat skeletal muscle. Am. J. Physiol. Heart Circ. Physiol. 278(5): H1480-H1489. PMID:10775125.
19. Goodenough, D.A., Goliger, J.A., and Paul, D.L. 1996. Connexins, connexons, and intercellular communication. Annu. Rev. Bio-chem. 65(1): 475-502. doi:10.1146/annurev.bi.65.070196. 002355. PMID:8811187.
20. Gustafsson, F., and Holstein-Rathlou, N. 1999. Conducted vasomotor responses in arterioles: characteristics, mechanisms and physiological significance. Acta Physiol. Scand. 167(1): 11-21. doi:10.1046/j.1365-201x.1999.00582.x. PMID:10519972.
21. Haddock, R.E., Grayson, T.H., Brackenbury, T.D., Meaney, K.R., Neylon, C.B., Sandow, S.L., and Hill, C.E. 2006. Endothelial coordination of cerebral vasomotion via myoendothelial gap junctions containing connexins 37 and 40. Am. J. Physiol. Heart Circ. Physiol. 291(5): H2047-H2056. doi:10.1152/ajpheart. 00484.2006. PMID:16815985.
22. Haefliger, J.A., Nicod, P., and Meda, P. 2004. Contribution of connexins to the function of the vascular wall. Cardiovasc. Res. 62(2): 345-356. doi:10.1016/j.cardiores.2003.11.015. PMID:15094354.
23. Heberlein, K.R., Straub, A.C., and Isakson, B.E. 2009. The myoendothelial junction: breaking through the matrix? Microcirculation, 16(4): 307-322. doi:10.1080/10739680902744404. PMID:19330678.
24. Hill, C.E., Rummery, N., Hickey, H., and Sandow, S.L. 2002. Heterogeneity in the distribution of vascular gap junctions and connexins: implications for function. Clin. Exp. Pharmacol. Physiol. 29(7): 620-625. doi:10.1046/j.1440-1681.2002.03699.x. PMID:12060107.
25. Hollenberg, S.M., Cunnion, R.E., and Zimmerberg, J. 1993. Nitric oxide synthase inhibition reverses arteriolar hyporesponsiveness to catecholamines in septic rats. Am. J. Physiol. 264(2 Pt 2): H660-H663. PMID:7680541.
26. Hou, C.J., Tsai, C.H., and Yeh, H.I. 2008. Endothelial connexins are down-regulated by atherogenic factors. Front. Biosci. 13: 3549-3557. doi:10.2741/2948. PMID:18508454.
27. Hu, J., and Cotgreave, I.A. 1997. Differential regulation of gap junctions by proinflammatory mediators in vitro. J. Clin. Invest. 99(10): 2312-2316. doi:10.1172/JCI119410. PMID:9153270.
28. Johnson, L.N., and Koval, M. 2009. Cross-talk between pulmonary injury, oxidant stress, and gap junctional communication. Antioxid. Redox Signal. 11(2): 355-367. doi:10.1089/ars.2008.2183. PMID:18816185.
29. Johnstone, S., Isakson, B., and Locke, D. 2009. Biological and biophysical properties of vascular connexin channels. Int. Rev. Cell Mol. Biol. 278: 69-118. doi:10.1016/S1937-6448(09)78002-5. PMID:19815177.
30. Kameritsch, P., Khandoga, N., Nagel, W., Hundhausen, C., Lidington, D., and Pohl, U. 2005. Nitric oxide specifically reduces the permeability of Cx37-containing gap junctions to small molecules. J. Cell. Physiol. 203(1): 233-242. doi:10.1002/jcp.20218. PMID:15481066.
31. Khadaroo, R.G., Kapus, A., Powers, K.A., Cybulsky, M.I., Marshall, J.C., and Rotstein, O.D. 2003. Oxidative stress reprograms lipopolysaccharide signaling via Src kinase-dependent pathway in RAW 264.7 macrophage cell line. J. Biol. Chem. 278(48): 47834-47841. doi:10.1074/jbc.M302660200. PMID:12896983.
32. Kumar, N.M., and Gilula, N.B. 1996. The gap junction communication channel. Cell, 84(3): 381-388. doi:10.1016/S0092-8674(00)81282-9. PMID:8608591.
33. Kurjiaka, D.T. 2004. The conduction of dilation along an arteriole is diminished in the cremaster muscle of hypertensive hamsters. J. Vasc. Res. 41(6): 517-524. doi:10.1159/000081808. PMID:15528934.
34. Laird, D.W. 2006. Life cycle of connexins in health and disease. Biochem. J. 394(3): 527-543. doi:10.1042/BJ20051922. PMID: 16492141.
35. Lam, C., Tyml, K., Martin, C., and Sibbald, W. 1994. Microvascular perfusion is impaired in a rat model of normotensive sepsis. J. Clin. Invest. 94(5): 2077-2083. doi:10.1172/JCI117562.PMID:7962554.
36. Lange, M., Enkhbaatar, P., Nakano, Y., and Traber, D.L. 2009. Role of nitric oxide in shock: the large animal perspective. Front. Biosci. 14: 1979-1989. doi:10.2741/3357. PMID:19273179.
37. Lidington, D., Ouellette, Y., and Tyml, K. 2000. Endotoxin increases intercellular resistance in microvascular endothelial cells by a tyrosine kinase pathway. J. Cell. Physiol. 185(1): 117-125. doi:10.1002/1097-4652(200010)185:1117::AID-JCP113.0. CO;2-7. PMID:10942525.
38. Lidington, D., Ouellette, Y., and Tyml, K. 2002a. Communication of agonist-induced electrical responses along 'capillaries' in vitro can be modulated by lipopolysaccharide, but not nitric oxide. J. Vasc. Res. 39(5): 405-413. doi:10.1159/000064519. PMID:12297703.
39. Lidington, D., Tyml, K., and Ouellette, Y. 2002b. Lipopolysaccharide-induced reductions in cellular coupling correlate with tyrosine phosphorylation of connexin 43. J. Cell. Physiol. 193(3): 373-379. doi:10.1002/jcp.10179. PMID:12384989.
40. Lidington, D., Ouellette, Y., Li, F., and Tyml, K. 2003. Conducted vasoconstriction is reduced in a mouse model of sepsis. J. Vasc. Res. 40(2): 149-158. doi:10.1159/000070712. PMID:12808351.
41. Lidington, D., Li, F., and Tyml, K. 2007. Deletion of neuronal NOS prevents impaired vasodilation in septic mouse skeletal muscle. Cardiovasc. Res. 74(1): 151-158. doi:10.1016/j.cardiores.2006.12.022. PMID:17258180.
42. 60src-mediated phosphorylation of connexin 43, a gap junction protein. J. Biol. Chem. 270(21): 12751-12761. doi:10. 1074/jbc.270.21.12751. PMID:7539006.
43. Looft-Wilson, R.C., Payne, G.W., and Segal, S.S. 2004. Connexin expression and conducted vasodilation along arteriolar endothelium in mouse skeletal muscle. J. Appl. Physiol. 97(3): 1152-1158. doi:10.1152/japplphysiol.00133.2004. PMID:15169746.
44. Lu, C., and McMahon, D.G. 1997. Modulation of hybrid bass retinal gap junctional channel gating by nitric oxide. J. Physiol. 499(Pt 3): 689-699. PMID:9130165.
45. McKinnon, R.L., Lidington, D., Bolon, M., Ouellette, Y., Kidder, G.M., and Tyml, K. 2006. Reduced arteriolar conducted vasoconstriction in septic mouse cremaster muscle is mediated by nNOS-derived NO. Cardiovasc. Res. 69(1): 236-244. doi:10.1016/j.cardiores.2005.09.003. PMID:16226732.
46. McKinnon, R.L., Lidington, D., and Tyml, K. 2007. Ascorbate inhibits reduced arteriolar conducted vasoconstriction in septic mouse cremaster muscle. Microcirculation, 14(7): 697-707. doi:10.1080/10739680701410389. PMID:17885995.
47. McKinnon, R.L., Bolon, M.L., Wang, H.X., Swarbreck, S., Kidder, G.M., Simon, A.M., and Tyml, K. 2009. Reduction of electrical coupling between microvascular endothelial cells by NO depends on connexin37. Am. J. Physiol. Heart Circ. Physiol. 297(1): H93-H101. doi:10.1152/ajpheart.01148.2008. PMID: 19429814.
48. Morel, S., Burnier, L., and Kwak, B.R. 2009. Connexins participate in the initiation and progression of atherosclerosis. Semin. Immunopathol. 31(1): 49-61. doi:10.1007/s00281-009-0147-6.PMID:19404645.
49. Moreno, A.P. 2004. Biophysical properties of homomeric and heteromultimeric channels formed by cardiac connexins. Cardiovasc. Res. 62(2): 276-286. doi:10.1016/j.cardiores.2004.03.003. PMID:15094348.
50. Mungrue, I.N., Bredt, D.S., Stewart, D.J., and Husain, M. 2003. From molecules to mammals: what's NOS got to do with it? Acta Physiol. Scand. 179(2): 123-135. doi:10.1046/j.1365-201X.2003.01182.x. PMID:14510775.
51. Nguyen, H.B., Rivers, E.P., Knoblich, B.P., Jacobsen, G., Muzzin, A., Ressler, J.A., and Tomlanovich, M.C. 2004. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit. Care Med. 32(8): 1637-1642. doi:10.1097/01.CCM.0000132904.35713.A7. PMID:15286537.
52. Ouellette, Y., Lidington, D., Naus, C.G., and Tyml, K. 2000. A new in vitro model for agonist-induced communication between microvascular endothelial cells. Microvasc. Res. 60(3): 222-231. doi:10.1006/mvre.2000.2263. PMID:11078638.
53. Patel, L.S., Mitchell, C.K., Dubinsky, W.P., and O'Brien, J. 2006. Regulation of gap junction coupling through the neuronal connexin Cx35 by nitric oxide and cGMP. Cell Commun. Adhes. 13(1-2): 41-54. doi:10.1080/15419060600631474. PMID:16613779.
54. Powers, K.A., Szászi, K., Khadaroo, R.G., Tawadros, P.S., Marshall, J.C., Kapus, A., and Rotstein, O.D. 2006. Oxidative stress generated by hemorrhagic shock recruits Toll-like receptor 4 to the plasma membrane in macrophages. J. Exp. Med. 203(8): 1951-1961. doi:10.1084/jem.20060943. PMID:16847070.
55. Rignault, S., Haefliger, J.A., Gasser, D., Markert, M., Nicod, P., Liaudet, L., et al. 2005. Sepsis up-regulates the expression of connexin 40 in rat aortic endothelium. Crit. Care Med. 33(6): 1302-1310. doi:10.1097/01.CCM.0000165968.47343.0D. PMID: 15942348.
56. Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., et al.; Early Goal-Directed Therapy Collaborative Group. 2001. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N. Engl. J. Med. 345(19): 1368-1377. doi:10.1056/NEJMoa010307. PMID:11794169.
57. Rose, K., Ouellette, Y., Bolon, M., and Tyml, K. 2005. Hypoxia/ reoxygenation reduces microvascular endothelial cell coupling by a tyrosine and MAP kinase dependent pathway. J. Cell. Physiol. 204(1): 131-138. doi:10.1002/jcp.20283. PMID:15672421.
58. Sáez, J.C., Berthoud, V.M., Moreno, A.P., and Spray, D.C. 1993. Gap junctions. Multiplicity of controls in differentiated and undifferentiated cells and possible functional implications. Adv. Second Messenger Phosphoprotein Res. 27: 163-198. PMID:8380327.
59. Sáez, J.C., Berthoud, V.M., Branes, M.C., Martinez, A.D., and Beyer, E.C. 2003. Plasma membrane channels formed by connexins: their regulation and functions. Physiol. Rev. 83(4): 1359-1400. PMID:14506308.
60. Sakr, Y., Dubois, M.J., De Backer, D., Creteur, J., and Vincent, J.L. 2004. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit. Care Med. 32(9): 1825-1831. doi:10.1097/01.CCM.0000138558. 16257.3F. PMID:15343008.
61. Simon, A.M., McWhorter, A.R., Chen, H., Jackson, C.L., and Ouellette, Y. 2004. Decreased intercellular communication and connexin expression in mouse aortic endothelium during lipopolysaccharide-induced inflammation. J. Vasc. Res. 41(4): 323-333. doi:10.1159/000079614. PMID:15249738.
62. Sohl, G., and Willecke, K. 2004. Gap junctions and the connexin protein family. Cardiovasc. Res. 62(2): 228-232. doi:10.1016/j. cardiores.2003.11.013. PMID:15094343.
63. Song, H., and Tyml, K. 1993. Evidence for sensing and integration of biological signals by the capillary network. Am. J. Physiol. 265(4 Pt 2): H1235-H1242. PMID:8238410.
64. Tran, C.H.T., and Welsh, D.G. 2009. Current perspective on differential communication in small resistance arteries. Can. J. Physiol. Pharmacol. 87(1): 21-28. doi:10.1139/Y08-104. PMID:19142212.
65. Tyml, K. 2006. Role of gap junctions in capillary-arteriolar communication. In Microvascular research: biology and pathology. Edited by D. Shepro and D.N. Granger. Elsevier Academic Press, Amsterdam. pp. 353-356.
66. Tyml, K., Yu, J., and McCormack, D.G. 1998. Capillary and arteriolar responses to local vasodilators are impaired in a rat model of sepsis. J. Appl. Physiol. 84(3): 837-844. PMID:9480941.
67. Tyml, K., Wang, X., Lidington, D., and Ouellette, Y. 2001. Lipopolysaccharide reduces intercellular coupling in vitro and arteriolar conducted response in vivo. Am. J. Physiol. Heart Circ. Physiol. 281(3): H1397-H1406. PMID:11514312.
68. Tyml, K., Li, F., and Wilson, J.X. 2008. Septic impairment of capillary blood flow requires nicotinamide adenine dinucleotide phosphate oxidase but not nitric oxide synthase and is rapidly reversed by ascorbate through an endothelial nitric oxide synthase-dependent mechanism. Crit. Care Med. 36(8): 2355-2362. doi:10.1097/CCM.0b013e31818024f6. PMID:18596627.
69. Wildhirt, S.M., Dudek, R.R., Suzuki, H., Pinto, V., Narayan, K.S., and Bing, R.J. 1995. Immunohistochemistry in the identification of nitric oxide synthase isoenzymes in myocardial infarction. Cardiovasc. Res. 29(4): 526-531. PMID:7540956.
70. Wu, F., Wilson, J.X., and Tyml, K. 2003. Ascorbate inhibits iNOS expression and preserves vasoconstrictor responsiveness in skeletal muscle of septic mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 285(1): R50-R56. PMID:12637347.
71. Wu, F., Wilson, J.X., and Tyml, K. 2004. Ascorbate protects against impaired arteriolar constriction in sepsis by inhibiting inducible nitric oxide synthase expression. Free Radic. Biol. Med. 37(8): 1282-1289. doi:10.1016/j.freeradbiomed.2004.06.025.PMID:15451067.
72. Wu, F., Tyml, K., and Wilson, J.X. 2008. iNOS expression requires NADPH oxidase-dependent redox signaling in microvascular endothelial cells. J. Cell. Physiol. 217(1): 207-214. doi:10.1002/ jcp.21495. PMID:18481258.
73. Xia, J., and Duling, B.R. 1995. Electromechanical coupling and the conducted vasomotor response. Am. J. Physiol. 269(6 Pt 2): H2022-H2030. PMID:8594912.
74. Xin, D., and Bloomfield, S.A. 2000. Effects of nitric oxide on horizontal cells in the rabbit retina. Vis. Neurosci. 17(5): 799-811. doi:10.1017/S0952523800175133. PMID:11153659.
75. Yamamoto, Y., Klemm, M.F., Edwards, F.R., and Suzuki, H. 2001. Intercellular electrical communication among smooth muscle and endothelial cells in guinea-pig mesenteric arterioles. J. Physiol. 535(1): 181-195. doi:10.1111/j.1469-7793.2001.00181.x. PMID:11507168.
76. Yeh, H.I., Rothery, S., Dupont, E., Coppen, S.R., and Severs, N.J. 1998. Individual gap junction plaques contain multiple connexins in arterial endothelium. Circ. Res. 83(12): 1248-1263. PMID:9851942.