TRPV4 channels: physiological and pathological role in cardiovascular system

Basic Research in Cardiology

Volumn 110, Issue 6, 2015, Pages 1-19

  Randhawa, Puneet Kaur ^a   Jaggi, Amteshwar Singh ^a  

^a PUNJABI UNIVERSITY   (India)

Author keywords

Cardiovascular; Collateral circulation; Hypertension; Hypoxic preconditioning; Mechanosensitive channels; TRPV4

Indexed keywords

TRPV4 PROTEIN, HUMAN; VANILLOID RECEPTOR;

ANIMAL; CARDIOVASCULAR DISEASE; CARDIOVASCULAR SYSTEM; HUMAN; METABOLISM;

ANIMALS; CARDIOVASCULAR DISEASES; CARDIOVASCULAR SYSTEM; HUMANS; TRPV CATION CHANNELS;

EID: 84957962969     PISSN: 03008428     EISSN: 14351803     Source Type: Journal    
DOI: 10.1007/s00395-015-0512-7     Document Type: Review

References (105)

1. Adapala RK, Thoppil RJ, Luther DJ, Paruchuri S, Meszaros JG, Chilian WM, Thodeti CK (2013) TRPV4 channels mediate cardiac fibroblast differentiation by integrating mechanical and soluble signals. J Mol Cell Cardiol 54:45–52. doi:10.1016/j.yjmcc.2012.10.016
2. Alessandri-Haber N, Dina OA, Joseph EK, Reichling D, Levine JD (2006) A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators. J Neurosci 26:3864–3874. doi:10.1523/JNEUROSCI.5385-05.2006
3. Arniges M, Fernández-Fernández JM, Albrecht N, Schaefer M, Valverde MA (2006) Human TRPV4 channel splice variants revealed a key role of ankyrin domains in multimerization and trafficking. J Biol Chem 281:1580–1586. doi:10.1074/jbc.M511456200
4. Ca channels, reducing arteriolar tone. Proc Natl Acad Sci USA 109:18174–18179. doi:10.1073/pnas.1211946109
5. Berridge MJ, Bootman MD, Roderick HL (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4:517–529. doi:10.1038/nrm1155
6. + channel in distal tubule function: regulation by TRPV4. PLoS ONE 9:e95149. doi:10.1371/journal.pone.0095149
7. 2+ entry and mitochondrial ROS signaling. Am J Physiol Heart Circ Physiol 302:H634–H642. doi:10.1152/ajpheart.00717.2011
8. Cabral PD, Garvin JL (2014) TRPV4 activation mediates flow-induced nitric oxide production in the rat thick ascending limb. Am J Physiol Renal Physiol 307:F666–F672. doi:10.1152/ajprenal.00619.2013
9. Caligiuri SP, Aukema HM, Ravandi A, Guzman R, Dibrov E, Pierce GN (2014) Flaxseed consumption reduces blood pressure in patients with hypertension by altering circulating oxylipins via an α-linolenic acid-induced inhibition of soluble epoxide hydrolase. Hypertension 64:53–59. doi:10.1161/HYPERTENSIONAHA.114.03179
10. Cappelli H, Adapala R, Thoppil R, Ohanyan V, Luli J, Luther D, Paruchiri S, Meszaros JG, Chilian W, Thodeti C (2014) TRPV4 deficiency protects myocardium following myocardial infarction and transverse aortic constriction. FASEB J. doi:10.1096/fj.1530-6860
11. Carreño FR, Ji LL, Cunningham JT (2009) Altered central TRPV4 expression and lipid raft association related to inappropriate vasopressin secretion in cirrhotic rats. Am J Physiol Regul Integr Comp Physiol 296:R454–R466. doi:10.1152/ajpregu.90460.2008
12. Demicheva E, Hecker M, Korff T (2008) Stretch-induced activation of the transcription factor activator protein-1 controls monocyte chemoattractant protein-1 expression during arteriogenesis. Circ Res 103:477–484. doi:10.1161/CIRCRESAHA.108.177782
13. + channels. J Cardiovasc Pharmacol 57:148–153. doi:10.1097/FJC.0b013e3181f580d9
14. Earley S, Pauyo T, Drapp R, Tavares MJ, Liedtke W, Brayden JE (2009) TRPV4-dependent dilation of peripheral resistance arteries influences arterial pressure. Am J Physiol Heart Circ Physiol 297:H1096–H1102. doi:10.1152/ajpheart.00241.2009
15. 2+ and ROS. Front Biosci (Landmark Ed) 14:1197–1218
16. Félétou M, Vanhoutte PM (2006) Endothelium-derived hyperpolarizing factor: where are we now? Arterioscler Thromb Vasc Biol 26:1215–1225. doi:10.1161/01.ATV.0000217611.81085.c5
17. Filosa JA, Yao X, Rath G (2013) TRPV4 and the regulation of vascular tone. J Cardiovasc Pharmacol 61:113–119. doi:10.1097/FJC.0b013e318279ba42
18. Fiorio Pla A, Ong HL, Cheng KT, Brossa A, Bussolati B, Lockwich T, Paria B, Munaron L, Ambudkar IS (2012) TRPV4 mediates tumor-derived endothelial cell migration via arachidonic acid-activated actin remodeling. Oncogene 31:200–212. doi:10.1038/onc.2011.231
19. Fleming I, Busse R (2003) Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am J Physiol Regul Integr Comp Physiol 284:R1–R12. doi:10.1152/ajpregu.00323.2002
20. Galvagni F, Orlandini M, Oliviero S (2013) Role of the AP-1 transcription factor FOSL1 in endothelial cells adhesion and migration. Cell Adh Migr 7:408–411. doi:10.4161/cam.25894
21. Gao F, Wang DH (2010) Impairment in function and expression of transient receptor potential vanilloid type 4 in Dahl salt-sensitive rats: significance and mechanism. Hypertension 55(4):1018–1025. doi:10.1161/HYPERTENSIONAHA.109.147710
22. + channels and sensory nerves. J Hypertens 28:102–110. doi:10.1097/HJH.0b013e328332b865
23. Goedicke-Fritz S, Kaistha A, Kacik M, Markert S, Hofmeister A, Busch C, Bänfer S, Jacob R, Grgic I, Hoyer J (2015) Evidence for functional and dynamic microcompartmentation of Cav-1/TRPV4/KCa in caveolae of endothelial cells. Eur J Cell Biol. doi:10.1016/j.ejcb.2015.06.002
24. 2+ signaling: old guests, new functions. Pflugers Arch 455:375–396. doi:10.1007/s00424-007-0296-1
25. Grant AD, Cottrell GS, Amadesi S, Trevisani M, Nicoletti P, Materazzi S, Altier C, Cenac N, Zamponi GW, Bautista-Cruz F, Lopez CB, Joseph EK, Levine JD, Liedtke W, Vanner S, Vergnolle N, Geppetti P, Bunnett NW, Robbins N, Koch SE, Rubinstein JF (2007) Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice. J Physiol 578:715–733. doi:10.1113/jphysiol.2006.121111
26. Gross GJ, Gauthier KM, Moore J, Campbell WB, Falck JR, Nithipatikom K (2009) Evidence for role of epoxyeicosatrienoic acids in mediating ischemic preconditioning and postconditioning in dog. Am J Physiol Heart Circ Physiol 297:H47–H52. doi:10.1152/ajpheart.01084.2008
27. Garcia-Elias A, Mrkonjić S, Jung C, Pardo-Pastor C, Vicente R, Valverde MA (2014) The TRPV4 channel. Handb Exp Pharmacol 222:293–319. doi:10.1007/978-3-642-54215-2_12
28. Hatano N, Itoh Y, Muraki K (2009) Cardiac fibroblasts have functional TRPV4 activated by 4α-phorbol 12, 13-didecanoate. Life Sci 85:808–814. doi:10.1016/j.lfs.2009.10.013
29. Heusch G, Libby P, Gersh B, Yellon D, Böhm M, Lopaschuk G, Opie L (2014) Cardiovascular remodelling in coronary artery disease and heart failure. Lancet 383:1933–1943. doi:10.1016/S0140-6736(14)60107-0
30. Heusch G (2015) Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning. Circ Res 116:674–699. doi:10.1161/CIRCRESAHA.116.305348
31. Hinz B, Gabbiani G (2010) Fibrosis: recent advances in myofibroblast biology and new therapeutic perspectives. Biol Rep 2:78. doi:10.3410/B2-78
32. Ho WS, Zheng X, Zhang DX (2015) Role of endothelial TRPV4 channels in vascular actions of the endocannabinoid, 2-arachidonoylglycerol. Br J Pharmacol. doi:10.1111/bph.13312
33. Inoue R, Jensen LJ, Shi J, Morita H, Nishida M, Honda A, Ito Y (2006) Transient receptor potential channels in cardiovascular function and disease. Circ Res 99:119–131. doi:10.1161/01.RES.0000233356.10630.8a
34. Ishikura T, Suzuki H, Shoguchi K, Koreeda Y, Aritomi T, Matsuura T, Yoshimura M, Ohkubo JI, Maruyama T, Kawasaki M, Ohnishi H, Sakai A, Mizuno A, Suzuki M, Ueta Y (2015) Possible involvement of TRPV1 and TRPV4 in nociceptive stimulation-induced nocifensive behavior and neuroendocrine response in mice. Brain Res Bull. doi:10.1016/j.brainresbull.2015.08.004
35. Jäderstad J, Brismar H, Herlenius E (2010) Hypoxic preconditioning increases gap-junctional graft and host communication. NeuroReport 21:1126–1132. doi:10.1097/WNR.0b013e328340a77b
36. Jian MY, King JA, Al-Mehdi AB, Liedtke W, Townsley MI (2008) High vascular pressure-induced lung injury requires P450 epoxygenase-dependent activation of TRPV4. Am J Respir Cell Mol Biol 38:386–392. doi:10.1165/rcmb.2007-0192OC
37. Jie P, Tian Y, Hong Z, Li L, Zhou L, Chen L, Chen L (2015) Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice. Front Cell Neurosci 9:141. doi:10.3389/fncel.2015.00141
38. Kinsman B, Cowles J, Lay J, Simmonds SS, Browning KN, Stocker SD (2014) Osmoregulatory thirst in mice lacking the transient receptor potential vanilloid type 1 (TRPV1) and/or type 4 (TRPV4) receptor. Am J Physiol Regul Integr Comp Physiol 307:R1092–R1100. doi:10.1152/ajpregu.00102.2014
39. Köhler R, Heyken WT, Heinau P, Schubert R, Si H, Kacik M, Busch C, Grgic I, Maier T, Hoyer J (2006) Evidence for a functional role of endothelial transient receptor potential V4 in shear stress-induced vasodilatation. Arterioscler Thromb Vasc Biol 26:1495–1502. doi:10.1161/01.ATV.0000225698.36212.6a
40. Köttgen M, Buchholz B, Garcia-Gonzalez MA, Kotsis F, Fu X, Doerken M, Boehlke C, Steffl D, Tauber R, Wegierski T, Nitschke R, Suzuki M, Kramer-Zucker A, Germino GG, Watnick T, Prenen J, Nilius B, Kuehn EW, Walz G (2008) TRPP2 and TRPV4 form a polymodal sensory channel complex. J Cell Biol 182:437–447. doi:10.1083/jcb.200805124
41. Lee H, Iida T, Mizuno A, Suzuki M, Caterina MJ (2005) Altered thermal selection behavior in mice lacking transient receptor potential vanilloid 4. J Neurosci 25:1304–1310. doi:10.1523/JNEUROSCI.4745.04.2005
42. Lei L, Cao X, Yang F, Shi DJ, Tang YQ, Zheng J, Wang K (2013) A TRPV4 channel C-terminal folding recognition domain critical for trafficking and function. J Biol Chem 288:10427–10439. doi:10.1074/jbc.M113.457291
43. Lin JH, Lou N, Kang N, Takano T, Hu F, Han X, Xu Q, Lovatt D, Torres A, Willecke K, Yang J, Kang J, Nedergaard M (2008) A central role of connexin 43 in hypoxic preconditioning. J Neurosci 28:681–695. doi:10.1523/JNEUROSCI.3827-07.2008
44. 2 is the transferrable factor mediating flow-induced dilation in human coronary arterioles. Circ Res 108:566–573. doi:10.1161/CIRCRESAHA.110.237636
45. 2 generation play a key role in flow-mediated dilation in human coronary resistancearteries. Circ Res 93:573–580. doi:10.1161/01.RES.0000091261.19387.AE
46. Loot AE, Popp R, Fisslthaler B, Vriens J, Nilius B, Fleming I (2008) Role of cytochrome P450-dependent transient receptor potential V4 activation in flow-induced vasodilatation. Cardiovasc Res 80:445–452. doi:10.1093/cvr/cvn207
47. 2+ influx. Arterioscler Thromb Vasc Biol 30:851–858. doi:10.1161/ATVBAHA.109.196584
48. Maiti D, Xu Z, Duh EJ (2008) Vascular endothelial growth factor induces MEF2C and MEF2-dependent activity in endothelial cells. Invest Ophthalmol Vis Sci 49:3640–3648. doi:10.1167/iovs.08-1760
49. 2+]i responses. Am J Physiol Heart Circ Physiol 281:H1759–H1766
50. Martin E, Dahan D, Cardouat G, Gillibert-Duplantier J, Marthan R, Savineau JP, Ducret T (2012) Involvement of TRPV1 and TRPV4 channels in migration of rat pulmonary arterial smooth muscle cells. Pflugers Arch 464:261–272. doi:10.1007/s00424-012-1136-5
51. Masuyama R, Vriens J, Voets T, Karashima Y, Owsianik G, Vennekens R, Lieben L, Torrekens S, Moermans K, Vanden Bosch A, Bouillon R, Nilius B, Carmeliet G (2008) TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts. Cell Metab 8:257–265. doi:10.1016/j.cmet.2008.08.002
52. 2+ uniporter contributes to acute ischemic neurodegeneration. Neurobiol Dis 68:137–144. doi:10.1016/j.nbd.2014.04.011
53. 2+ influx and vasodilation in response to shear stress. Am J Physiol Heart Circ Physiol 298:H466–H476. doi:10.1152/ajpheart.00854.2009
54. (+) channels. Circulation 103:1992–1998. doi:10.1161/01.CIR.103.15.1992
55. Mizuno A, Matsumoto N, Imai M, Suzuki M (2003) Impaired osmotic sensation in mice lacking TRPV4. Am J Physiol Cell Physiol 285:C96–C101. doi:10.1152/ajpcell.00559.2002
56. Mueller-Tribbensee SM, Karna M, Khalil M, Neurath MF, Reeh PW, Engel MA (2015) Differential contribution of TRPA1, TRPV4 and TRPM8 to colonic nociception in mice. PLoS ONE 10:e0128242. doi:10.1371/journal.pone.0128242
57. Muramatsu S, Wakabayashi M, Ohno T, Amano K, Ooishi R, Sugahara T, Shiojiri S, Tashiro K, Suzuki Y, Nishimura R, Kuhara S, Sugano S, Yoneda T, Matsuda A (2007) Functional gene screening system identified TRPV4 as a regulator of chondrogenic differentiation. J Biol Chem 282:32158–32167. doi:10.1074/jbc.M706158200
58. Nishijima Y, Zheng X, Lund H, Suzuki M, Mattson DL, Zhang DX (2014) Characterization of blood pressure and endothelial function in TRPV4-deficient mice with l-NAME- and angiotensin II-induced hypertension. Physiol Rep 2:e00199. doi:10.1002/phy2.199
59. Nozadze I, Tsiklauri N, Gurtskaia G, Tsagareli MG (2015) Role of thermo TRPA1 and TRPV1 channels in heat, cold, and mechanical nociception of rats. Behav Pharmacol
60. O’Conor CJ, Griffin TM, Liedtke W, Guilak F (2013) Increased susceptibility of Trpv4-deficient mice to obesity and obesity-induced osteoarthritis with very high-fat diet. Ann Rheum Dis 72:300–304. doi:10.1136/annrheumdis-2012-202272
61. Okahara K, Sun B, Kambayashi J (1998) Upregulation of prostacyclin synthesis-related gene expression by shear stress in vascular endothelial cells. Arterioscler Thromb Vasc Biol 18:1922–1926. doi:10.1161/01.ATV.18.12.1922
62. Paniagua OA, Bryant MB, Panza JA (2001) Role of endothelial nitric oxide in shear stress-induced vasodilation of human microvasculature: diminished activity in hypertensive and hypercholesterolemic patients. Circulation 103:1752–175812. doi:10.1161/01.CIR.103.13.1752
63. Parpaite T, Cardouat G, Mauroux M, Gillibert-Duplantier J, Robillard P, Quignard JF, Marthan R, Savineau JP, Ducret T (2015) Effect of hypoxia on TRPV1 and TRPV4 channels in rat pulmonary arterial smooth muscle cells. Pflugers Arch
64. Passier R, Zeng H, Frey N, Naya FJ, Nicol RL, McKinsey TA, Overbeek P, Richardson JA, Grant SR, Olson EN (2000) CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo. J Clin Invest 105:1395–1406. doi:10.1172/JCI8551
65. Peixoto-Neves D, Wang Q, Leal-Cardoso JH, Rossoni LV, Jaggar JH (2015) Eugenol dilates mesenteric arteries and reduces systemic BP by activating endothelial cell TRPV4 channels. Br J Pharmacol 172:3484–3494. doi:10.1111/bph.13156
66. Peng TI, Jou MJ (2010) Oxidative stress caused by mitochondrial calcium overload. Ann N Y Acad Sci 1201:183–188. doi:10.1111/j.1749-6632.2010.05634.x
67. Pokreisz P, Fleming I, Kiss L, Barbosa-Sicard E, Fisslthaler B, Falck JR, Hammock BD, Kim IH, Szelid Z, Vermeersch P, Gillijns H, Pellens M, Grimminger F, van Zonneveld AJ, Collen D, Busse R, Janssens S (2006) Cytochrome P450 epoxygenase gene function in hypoxic pulmonary vasoconstriction and pulmonary vascular remodeling. Hypertension 47:762–770. doi:10.1161/01.HYP.0000208299.62535.58
68. Premkumar KV, Chaube SK (2014) RyR channel-mediated increase of cytosolic free calcium level signals cyclin B1 degradation during abortive spontaneous egg activation in rat. In Vitro Cell Dev Biol Anim 50:640–647. doi:10.1007/s11626-014-9749-y
69. Rahaman SO, Grove LM, Paruchuri S, Southern BD, Abraham S, Niese KA, Scheraga RG, Ghosh S, Thodeti CK, Zhang DX, Moran MM, Schilling WP, Tschumperlin DJ, Olman MA (2014) TRPV4 mediates myofibroblast differentiation and pulmonary fibrosis in mice. J Clin Invest 124:5225–5238. doi:10.1172/JCI75331
70. Randhawa PK, Jaggi AS (2015) TRPV1 and TRPV4 channels: potential therapeutic targets for ischemic conditioning-induced cardioprotection. Eur J Pharmacol 746:180–185. doi:10.1016/j.ejphar.2014.11.010
71. Rath G, Saliez J, Behets G, Romero-Perez M, Leon-Gomez E, Bouzin C, Vriens J, Nilius B, Feron O, Dessy C (2012) Vascular hypoxic preconditioning relies on TRPV4 dependent calcium influx and proper intercellular gap junctions communication. Arterioscler ThrombVasc Biol 32:2241–2249. doi:10.1161/ATVBAHA.112.252783
72. Robbins N, Koch SE, Rubinstein JF (2013) Targeting TRPV1 and TRPV2 for potential therapeutic interventions in cardiovascular disease. Transl Res 161:469–476. doi:10.1016/j.trsl.2013.02.003
73. 2+ for cancer cell proliferation and survival. Nat Rev Cancer 8:361–375. doi:10.1038/nrc2374
74. 2+ signals and gap junction function are regulated by caveolin in endothelial cells. Circulation 117:1065–1074. doi:10.1161/CIRCULATIONAHA.107.731679
75. Schulz R, Boengler K, Totzeck A, Luo Y, Garcia-Dorado D, Heusch G (2007) Connexin 43 in ischemic pre- and postconditioning. Heart Fail Rev 12:261–266. doi:10.1007/s10741-007-9032-3
76. Shiode N, Morishima N, Nakayama K, Yamagata T, Matsuura H, Kajiyama G (1996) Flow-mediated vasodilation of human epicardial coronary arteries: effect of inhibition of nitric oxide synthesis. J Am Coll Cardiol 27:304–310. doi:10.1016/0735-1097(95)00465-3
77. Sokabe T, Fukumi-Tominaga T, Yonemura S, Mizuno A, Tominaga M (2010) The TRPV4 channel contributes to intercellular junction formation in keratinocytes. J Biol Chem 285:18749–18758. doi:10.1074/jbc.M110.103606
78. Song Y, Zhan L, Yu M, Huang C, Meng X, Ma T, Zhang L, Li J (2014) TRPV4 channel inhibits TGF-β1-induced proliferation of hepatic stellate cells. PLoS ONE 9:e101179. doi:10.1371/journal.pone.0101179
79. 2+ signals through endothelial TRPV4 channels regulate vascular function. Science 336:597–601. doi:10.1126/science.1216283
80. Sonkusare SK, Dalsgaard T, Bonev AD, Hill-Eubanks DC, Kotlikoff MI, Scott JD, Santana LF, Nelson MT (2014) AKAP150-dependent cooperative TRPV4 channel gating is central to endothelium-dependent vasodilation and is disrupted in hypertension. Sci Signal 7:66. doi:10.1126/scisignal.2005052
81. Sousa-Valente J, Andreou AP, Urban L, Nagy I (2014) Transient receptor potential ion channels in primary sensory neurons as targets for novel analgesics. Br J Pharmacol 171:2508–2527. doi:10.1111/bph.12532
82. Strotmann R, Harteneck C, Nunnenmacher K, Schultz G, Plant TD (2000) OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat Cell Biol 2:695–702. doi:10.1038/35036318
83. Sukumaran SV, Singh TU, Parida S, Narasimha Reddy ChE, Thangamalai R, Kandasamy K, Singh V, Mishra SK (2013) TRPV4 channel activation leads to endothelium-dependent relaxation mediated by nitric oxide and endothelium-derived hyperpolarizing factor in rat pulmonary artery. Pharmacol Res 78:18–27. doi:10.1016/j.phrs.2013.09.005
84. Sun D, Liu H, Yan C, Jacobson A, Ojaimi C, Huang A et al (2006) COX-2 contributes to the maintenance of flow-induced dilation in arterioles of eNOS-knockout mice. Am J Physiol Heart Circ Physiol 291:H1429–H1435. doi:10.1152/ajpheart.01130.2005
85. Suzuki M, Mizuno A, Kodaira K, Imai M (2003) Impaired pressure sensation in mice lacking TRPV4. J Biol Chem 278:22664–22668. doi:10.1074/jbc.M302561200
86. Tabuchi K, Suzuki M, Mizuno A, Hara A (2005) Hearing impairment in TRPV4 knockout mice. Neurosci Lett 382:304–308. doi:10.1016/j.neulet.2005.03.035
87. Thodeti CK, Matthews B, Ravi A, Mammoto A, Ghosh K, Bracha AL, Ingber DE (2009) TRPV4 channels mediate cyclic strain-induced endothelial cell reorientation through integrin-to-integrin signaling. Circ Res 104:1123–1130. doi:10.1161/CIRCRESAHA.108.192930
88. Thorneloe KS, Cheung M, Bao W, Alsaid H, Lenhard S, Jian MY, Costell M, Maniscalco-Hauk K, Krawiec JA, Olzinski A, Gordon E, Lozinskaya I, Elefante L, Qin P, Matasic DS, James C, Tunstead J, Donovan B, Kallal L, Waszkiewicz A, Vaidya K, Davenport EA, Larkin J, Burgert M, Casillas LN, Marquis RW, Ye G, Eidam HS, Goodman KB, Toomey JR, Roethke TJ, Jucker BM, Schnackenberg CG, Townsley MI, Lepore JJ, Willette RN (2012) An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci Transl Med 4:159ra148. doi:10.1126/scitranslmed.3004276
89. Traaseth N, Elfering S, Solien J, Haynes V, Giulivi C (2004) Role of calcium signaling in the activation of mitochondrial nitric oxide synthase and citric acid cycle. Biochim Biophys Acta 1658:64–71. doi:10.1016/j.bbabio.2004.04.015
90. Troidl K, Szardien S, Rolf A, Schmitz-Rixen T, Schaper W, Hamm CW, Elsässer A, Möllmann H (2010) Calcium-dependent signalling is essential during collateral growth in the pig hind limb-ischemia model. J Mol Cell Cardiol 49:142–151. doi:10.1016/j.yjmcc.2010.03.021
91. Troidl C, Troidl K, Schierling W, Cai WJ, Nef H, Möllmann H, Kostin S, Schimanski S, Hammer L, Elsässer A, Schmitz-Rixen T, Schaper W (2009) Trpv4 induces collateral vessel growth during regeneration of the arterial circulation. J Cell Mol Med 13:2613–2621. doi:10.1111/j.1582-4934.2008.00579.x
92. 2+ permeable cation channel TRPV4 by cytochrome P450 epoxygenases in vascular endothelium. Circ Res 97:908–915. doi:10.1161/01.RES.0000187474.47805.30
93. Watanabe H, Vriens J, Prenen J, Droogmans G, Voets T, Nilius B (2003) Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature 424:434–438. doi:10.1038/nature01807
94. Yan H, Hao S, Sun X, Zhang D, Gao X, Yu Z, Li K, Hang CH (2015) Blockage of mitochondrial calcium uniporter prevents iron accumulation in a model of experimental subarachnoid hemorrhage. Biochem Biophys Res Commun 456:835–840. doi:10.1016/j.bbrc.2014.12.073
95. Yang XR, Lin AH, Hughes JM, Flavahan NA, Cao YN, Liedtke W et al (2012) Upregulation of osmo-mechanosensitive TRPV4 channel facilitates chronic hypoxia-induced myogenic tone and pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 302:L555–L568. doi:10.1152/ajplung.00005.2011
96. Yao X, Garland CJ (2005) Recent developments in vascular endothelial cell transient receptor potential channels. Circ Res 97:853–863. doi:10.1161/01.RES.0000187473.85419.3e
97. Yoshida T, Inoue R, Morii T, Takahashi N, Yamamoto S, Hara Y, Tominaga M, Shimizu S, Sato Y, Mori Y (2006) Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nat Chem Biol 2:596–607. doi:10.1038/nchembio821
98. Yu Z, Xu F, Huse LM, Morisseau C, Draper AJ, Newman JW, Parker C, Graham L, Engler MM, Hammock BD, Zeldin DC, Kroetz DL (2000) Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids. Circ Res 87:992–998. doi:10.1161/01.RES.87.11.992
99. Zaichuk TA, Shroff EH, Emmanuel R, Filleur S, Nelius T, Volpert OV (2004) Nuclear factor of activated T cells balances angiogenesis activation and inhibition. J Exp Med 199:1513–1522. doi:10.1084/jem.20040474
100. Zaika O, Mamenko M, Berrout J, Boukelmoune N, O’Neil RG, Pochynyuk O (2013) TRPV4 dysfunction promotes renal cystogenesis in autosomal recessive polycystic kidney disease. J Am Soc Nephrol 24:604–616. doi:10.1681/ASN.2012050442
101. Zhang DX, Gutterman DD (2007) Mitochondrial reactive oxygen species-mediated signaling in endothelial cells. Am J Physiol Heart Circ Physiol 292:H2023–H2031. doi:10.1152/ajpheart.01283.2006
102. Zhang DX, Mendoza SA, Bubolz AH, Mizuno A, Ge ZD, Li R, Warltier DC, Suzuki M, Gutterman DD (2009) Transient receptor potential vanilloid type 4-deficient mice exhibit impaired endothelium-dependent relaxation induced by acetylcholine in vitro and in vivo. Hypertension 53:532–538. doi:10.1161/HYPERTENSIONAHA.108.127100
103. 2+ sparklets stimulate airway smooth muscle cell proliferation. Am J Respir Cell Mol Biol 50:1064–1075. doi:10.1165/rcmb.2013-0416OC
104. 2+ entry. J Am Heart Assoc 2:e000080. doi:10.1161/JAHA.113.000080
105. Zheng YM, Wang QS, Rathore R, Zhang WH, Mazurkiewicz JE, Sorrentino V, Singer HA, Kotlikoff MI, Wang YX (2005) Type-3 ryanodine receptors mediate hypoxia-, but not neurotransmitter-induced calcium release and contraction in pulmonary artery smooth muscle cells. J Gen Physiol 125:427–440. doi:10.1085/jgp.200409232