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Redox Mechanisms Influencing cGMP Signaling in Pulmonary Vascular Physiology and Pathophysiology

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Pulmonary Vasculature Redox Signaling in Health and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 967))

Abstract

The soluble form of guanylate cyclase (sGC) and cGMP signaling are major regulators of pulmonary vasodilation and vascular remodeling that protect the pulmonary circulation from hypertension development. Nitric oxide, reactive oxygen species, thiol and heme redox, and heme biosynthesis control mechanisms regulating the production of cGMP by sGC. In addition, a cGMP-independent mechanism regulates protein kinase G through thiol oxidation in manner controlled by peroxide metabolism and NADPH redox. Multiple aspects of these regulatory processes contribute to physiological and pathophysiological regulation of the pulmonary circulation, and create potentially novel therapeutic targets for the treatment of pulmonary vascular disease.

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Abbreviations

ALA:

δ-Aminolevulinic acid

Ang II:

Angiotensin II

Ca2+ :

Calcium

cGMP:

Cyclic guanosine monophosphate

DHEA:

Dehydroepiandrosterone

EDNO:

Endothelium-derived nitric oxide

EDRF:

Endothelium-derived relaxing factor

eNOS:

Endothelial nitric oxide synthase

ET-1:

Endothelin-1

Fe2+ :

Ferrous

FECH:

Ferrochelatase

H2O2 :

Hydrogen peroxide

NAD:

Nicotinamide adenine dinucleotide

NADP:

Nicotinamide adenine dinucleotide phosphate

NO:

Nitric oxide

NOX:

NADPH oxidase

PA:

Pulmonary arteries

PH:

Pulmonary hypertension

PKG:

Protein kinase G

PKG1α:

Protein kinase G 1α

PpIX:

Protoporphyrin IX

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

sGC:

Soluble guanylate cyclase

SOD:

Superoxide dismutase

VEGF:

Vascular endothelial growth factor

VSM:

Vascular smooth muscle

VSMC:

Vascular smooth muscle cell

Zn-PpIX:

Zinc-protoporphyrin IX

References

  1. Waldman, S. A., & Murad, F. (1987). Cyclic GMP synthesis and function. Pharmacological Reviews, 39(3), 163–196.

    CAS  PubMed  Google Scholar 

  2. Craven, P. A., & DeRubertis, F. R. (1978). Restoration of the responsiveness of purified guanylate cyclase to nitrosoguanidine, nitric oxide, and related activators by heme and hemeproteins. Evidence for involvement of the paramagnetic nitrosyl-heme complex in enzyme activation. The Journal of Biological Chemistry, 253(23), 8433–8443.

    CAS  PubMed  Google Scholar 

  3. Ignarro, L. J., Lippton, H., Edwards, J. C., et al. (1981). Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: Evidence for the involvement of S-nitrosothiols as active intermediates. The Journal of Pharmacology and Experimental Therapeutics, 218(3), 739–749.

    CAS  PubMed  Google Scholar 

  4. Ignarro, L. J., Burke, T. M., Wood, K. S., et al. (1984). Association between cyclic GMP accumulation and acetylcholine-elicited relaxation of bovine intrapulmonary artery. The Journal of Pharmacology and Experimental Therapeutics, 228(3), 682–690.

    CAS  PubMed  Google Scholar 

  5. Ignarro, L. J., Buga, G. M., Wood, K. S., et al. (1987). Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proceedings of the National Academy of Sciences of the United States of America, 84(24), 9265–9269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Neo, B. H., Kandhi, S., Ahmad, M., et al. (2010). Redox regulation of guanylate cyclase and protein kinase G in vascular responses to hypoxia. Respiratory Physiology & Neurobiology, 174(3), 259–264. doi:10.1016/j.resp.2010.08.024.

    Article  CAS  Google Scholar 

  7. Neo, B. H., Patel, D., Kandhi, S., et al. (2013). Roles for cytosolic NADPH redox in regulating pulmonary artery relaxation by thiol oxidation-elicited subunit dimerization of protein kinase G1alpha. American Journal of Physiology. Heart and Circulatory Physiology, 305(3), H330–H343. doi:10.1152/ajpheart.01010.2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wolin, M. S. (2009). Reactive oxygen species and the control of vascular function. American Journal of Physiology. Heart and Circulatory Physiology, 296(3), H539–H549. doi:10.1152/ajpheart.01167.2008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Patel, D., Alhawaj, R., & Wolin, M. S. (2014). Exposure of mice to chronic hypoxia attenuates pulmonary arterial contractile responses to acute hypoxia by increases in extracellular hydrogen peroxide. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 307(4), R426–R433. doi:10.1152/ajpregu.00257.2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Alhawaj, R., Patel, D., Kelly, M. R., et al. (2015). Heme biosynthesis modulation via delta-aminolevulinic acid administration attenuates chronic hypoxia-induced pulmonary hypertension. American Journal of Physiology. Lung Cellular and Molecular Physiology, 308(7), L719–L728. doi:10.1152/ajplung.00155.2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Coggins, M. P., & Bloch, K. D. (2007). Nitric oxide in the pulmonary vasculature. Arteriosclerosis, Thrombosis, and Vascular Biology, 27(9), 1877–1885. ATVBAHA.107.142943 [pii].

    Article  CAS  PubMed  Google Scholar 

  12. Deruelle, P., Grover, T. R., & Abman, S. H. (2005). Pulmonary vascular effects of nitric oxide-cGMP augmentation in a model of chronic pulmonary hypertension in fetal and neonatal sheep. American Journal of Physiology. Lung Cellular and Molecular Physiology, 289(5), L798–L806. 00119.2005 [pii].

    Article  CAS  PubMed  Google Scholar 

  13. Deruelle, P., Grover, T. R., Storme, L., et al. (2005). Effects of BAY 41-2272, a soluble guanylate cyclase activator, on pulmonary vascular reactivity in the ovine fetus. American Journal of Physiology. Lung Cellular and Molecular Physiology, 288(4), L727–L733. 00409.2004 [pii].

    Article  CAS  PubMed  Google Scholar 

  14. Burgoyne, J. R., Madhani, M., Cuello, F., et al. (2007). Cysteine redox sensor in PKGIa enables oxidant-induced activation. Science, 317(5843), 1393–1397. 1144318 [pii].

    Article  CAS  PubMed  Google Scholar 

  15. Lincoln, T. M., Dey, N., & Sellak, H. (2001). Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: From the regulation of tone to gene expression. Journal of Applied Physiology, 91(3), 1421–1430.

    CAS  PubMed  Google Scholar 

  16. Rainer, P. P., & Kass, D. A. (2016). Old dog, new tricks: Novel cardiac targets and stress regulation by protein kinase G. Cardiovascular Research, 111(2), 154–162. doi:10.1093/cvr/cvw107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chettimada, S., Rawat, D. K., Dey, N., et al. (2012). Glc-6-PD and PKG contribute to hypoxia-induced decrease in smooth muscle cell contractile phenotype proteins in pulmonary artery. American Journal of Physiology. Lung Cellular and Molecular Physiology, 303(1), L64–L74. doi:10.1152/ajplung.00002.2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gupte, R. S., Rawat, D. K., Chettimada, S., et al. (2010). Activation of glucose-6-phosphate dehydrogenase promotes acute hypoxic pulmonary artery contraction. The Journal of Biological Chemistry, 285(25), 19561–19571. doi:10.1074/jbc.M109.092916.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Garg, U. C., & Hassid, A. (1989). Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. The Journal of Clinical Investigation, 83(5), 1774–1777. doi:10.1172/JCI114081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kolpakov, V., Gordon, D., & Kulik, T. J. (1995). Nitric oxide-generating compounds inhibit total protein and collagen synthesis in cultured vascular smooth muscle cells. Circulation Research, 76(2), 305–309.

    Article  CAS  PubMed  Google Scholar 

  21. Tanner, F. C., Meier, P., Greutert, H., et al. (2000). Nitric oxide modulates expression of cell cycle regulatory proteins: A cytostatic strategy for inhibition of human vascular smooth muscle cell proliferation. Circulation, 101(16), 1982–1989.

    Article  CAS  PubMed  Google Scholar 

  22. Ambalavanan, N., Mariani, G., Bulger, A., et al. (1999). Role of nitric oxide in regulating neonatal porcine pulmonary artery smooth muscle cell proliferation. Biology of the Neonate, 76(5), 291–300. 14171 [pii].

    Article  CAS  PubMed  Google Scholar 

  23. Jourdan, K. B., Evans, T. W., Lamb, N. J., et al. (1999). Autocrine function of inducible nitric oxide synthase and cyclooxygenase-2 in proliferation of human and rat pulmonary artery smooth-muscle cells: Species variation. American Journal of Respiratory Cell and Molecular Biology, 21(1), 105–110. doi:10.1165/ajrcmb.21.1.3502.

    Article  CAS  PubMed  Google Scholar 

  24. Krick, S., Platoshyn, O., Sweeney, M., et al. (2002). Nitric oxide induces apoptosis by activating K+ channels in pulmonary vascular smooth muscle cells. American Journal of Physiology. Heart and Circulatory Physiology, 282(1), H184–H193.

    CAS  PubMed  Google Scholar 

  25. Farrow, K. N., Wedgwood, S., Lee, K. J., et al. (2010). Mitochondrial oxidant stress increases PDE5 activity in persistent pulmonary hypertension of the newborn. Respiratory Physiology & Neurobiology, 174(3), 272–281. doi:10.1016/j.resp.2010.08.018.

    Article  CAS  Google Scholar 

  26. Ballou, D. P., Zhao, Y., Brandish, P. E., et al. (2002). Revisiting the kinetics of nitric oxide (NO) binding to soluble guanylate cyclase: The simple NO-binding model is incorrect. Proceedings of the National Academy of Sciences of the United States of America, 99(19), 12097–12101. doi:10.1073/pnas.192209799.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Herzik, M. A., Jr., Jonnalagadda, R., Kuriyan, J., et al. (2014). Structural insights into the role of iron-histidine bond cleavage in nitric oxide-induced activation of H-NOX gas sensor proteins. Proceedings of the National Academy of Sciences of the United States of America, 111(40), E4156–E4164. doi:10.1073/pnas.1416936111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Schrammel, A., Behrends, S., Schmidt, K., et al. (1996). Characterization of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one as a heme-site inhibitor of nitric oxide-sensitive guanylyl cyclase. Molecular Pharmacology, 50(1), 1–5.

    CAS  PubMed  Google Scholar 

  29. Stasch, J. P., Schmidt, P. M., Nedvetsky, P. I., et al. (2006). Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels. The Journal of Clinical Investigation, 116(9), 2552–2561. doi:10.1172/JCI28371.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Stasch, J. P., Pacher, P., & Evgenov, O. V. (2011). Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation, 123(20), 2263–2273. doi:10.1161/CIRCULATIONAHA.110.981738.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Meurer, S., Pioch, S., Pabst, T., et al. (2009). Nitric oxide-independent vasodilator rescues heme-oxidized soluble guanylate cyclase from proteasomal degradation. Circulation Research, 105(1), 33–41. doi:10.1161/CIRCRESAHA.109.198234.

    Article  CAS  PubMed  Google Scholar 

  32. Ghosh, A., & Stuehr, D. J. (2017). Regulation of sGC via hsp90, cellular heme, sGC agonists, and NO: New pathways and clinical perspectives. Antioxidants & Redox Signaling, 26(4), 182–190. doi:10.1089/ars.2016.6690.

    Article  CAS  Google Scholar 

  33. Beuve, A. (2017). Thiol-based redox modulation of soluble guanylyl cyclase, the nitric oxide receptor. Antioxidants & Redox Signaling, 26(3), 137–149. doi:10.1089/ars.2015.6591.

    Article  CAS  Google Scholar 

  34. Wolin, M. S., Ahmad, M., & Gupte, S. A. (2005). Oxidant and redox signaling in vascular oxygen sensing mechanisms: Basic concepts, current controversies, and potential importance of cytosolic NADPH. American Journal of Physiology. Lung Cellular and Molecular Physiology, 289(2), L159–L173. 289/2/L159 [pii].

    Article  CAS  PubMed  Google Scholar 

  35. Mittal, M., Gu, X. Q., Pak, O., et al. (2012). Hypoxia induces Kv channel current inhibition by increased NADPH oxidase-derived reactive oxygen species. Free Radical Biology & Medicine, 52(6), 1033–1042. doi:10.1016/j.freeradbiomed.2011.12.004.

    Article  CAS  Google Scholar 

  36. Neo, B. H., Kandhi, S., & Wolin, M. S. (2011). Roles for redox mechanisms controlling protein kinase G in pulmonary and coronary artery responses to hypoxia. American Journal of Physiology. Heart and Circulatory Physiology, 301(6), H2295–H2304. doi:10.1152/ajpheart.00624.2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gupte, S. A., Kaminski, P. M., Floyd, B., et al. (2005). Cytosolic NADPH may regulate differences in basal Nox oxidase-derived superoxide generation in bovine coronary and pulmonary arteries. American Journal of Physiology. Heart and Circulatory Physiology, 288(1), H13–H21. doi:10.1152/ajpheart.00629.2004.

    Article  CAS  PubMed  Google Scholar 

  38. Fineman, J. R., Soifer, S. J., & Heymann, M. A. (1995). Regulation of pulmonary vascular tone in the perinatal period. Annual Review of Physiology, 57, 115–134. doi:10.1146/annurev.ph.57.030195.000555.

    Article  CAS  PubMed  Google Scholar 

  39. Dschietzig, T., Richter, C., Bartsch, C., et al. (2001). Flow-induced pressure differentially regulates endothelin-1, urotensin II, adrenomedullin, and relaxin in pulmonary vascular endothelium. Biochemical and Biophysical Research Communications, 289(1), 245–251. doi:10.1006/bbrc.2001.5946.

    Article  CAS  PubMed  Google Scholar 

  40. Mata-Greenwood, E., Meyrick, B., Soifer, S. J., et al. (2003). Expression of VEGF and its receptors Flt-1 and Flk-1/KDR is altered in lambs with increased pulmonary blood flow and pulmonary hypertension. American Journal of Physiology. Lung Cellular and Molecular Physiology, 285(1), L222–L231. doi:10.1152/ajplung.00388.2002.

    Article  CAS  PubMed  Google Scholar 

  41. Mata-Greenwood, E., Meyrick, B., Steinhorn, R. H., et al. (2003). Alterations in TGF-beta1 expression in lambs with increased pulmonary blood flow and pulmonary hypertension. American Journal of Physiology. Lung Cellular and Molecular Physiology, 285(1), L209–L221. doi:10.1152/ajplung.00171.2002.

    Article  CAS  PubMed  Google Scholar 

  42. Wedgwood, S., Devol, J. M., Grobe, A., et al. (2007). Fibroblast growth factor-2 expression is altered in lambs with increased pulmonary blood flow and pulmonary hypertension. Pediatric Research, 61(1), 32–36. doi:10.1203/01.pdr.0000250013.77008.28.

    Article  CAS  PubMed  Google Scholar 

  43. Dudzinski, D. M., Igarashi, J., Greif, D., et al. (2006). The regulation and pharmacology of endothelial nitric oxide synthase. Annual Review of Pharmacology and Toxicology, 46, 235–276. doi:10.1146/annurev.pharmtox.44.101802.121844.

    Article  CAS  PubMed  Google Scholar 

  44. Cerqueira, F. M., Brandizzi, L. I., Cunha, F. M., et al. (2012). Serum from calorie-restricted rats activates vascular cell through enhanced insulin signaling mediated by adiponectin. PLoS One, 7(2), e31155. doi:10.1371/journal.pone.0031155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Egom, E. E., Mohamed, T. M., Mamas, M. A., et al. (2011). Activation of Pak1/Akt/eNOS signaling following sphingosine-1-phosphate release as part of a mechanism protecting cardiomyocytes against ischemic cell injury. American Journal of Physiology. Heart and Circulatory Physiology, 301(4), H1487–H1495. doi:10.1152/ajpheart.01003.2010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Murata, T., Sato, K., Hori, M., et al. (2002). Decreased endothelial nitric-oxide synthase (eNOS) activity resulting from abnormal interaction between eNOS and its regulatory proteins in hypoxia-induced pulmonary hypertension. The Journal of Biological Chemistry, 277(46), 44085–44092. doi:10.1074/jbc.M205934200.

    Article  CAS  PubMed  Google Scholar 

  47. Gangopahyay, A., Oran, M., Bauer, E. M., et al. (2011). Bone morphogenetic protein receptor II is a novel mediator of endothelial nitric-oxide synthase activation. The Journal of Biological Chemistry, 286(38), 33134–33140. doi:10.1074/jbc.M111.274100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Steudel, W., Scherrer-Crosbie, M., Bloch, K. D., et al. (1998). Sustained pulmonary hypertension and right ventricular hypertrophy after chronic hypoxia in mice with congenital deficiency of nitric oxide synthase 3. The Journal of Clinical Investigation, 101(11), 2468–2477. doi:10.1172/JCI2356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Gizi, A., Papassotiriou, I., Apostolakou, F., et al. (2011). Assessment of oxidative stress in patients with sickle cell disease: The glutathione system and the oxidant-antioxidant status. Blood Cells, Molecules & Diseases, 46(3), 220–225. doi:10.1016/j.bcmd.2011.01.002.

    Article  CAS  Google Scholar 

  50. Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008). The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nature Reviews. Drug Discovery, 7(2), 156–167. doi:10.1038/nrd2466.

    Article  CAS  PubMed  Google Scholar 

  51. Spiegelhalder, B., Eisenbrand, G., & Preussmann, R. (1976). Influence of dietary nitrate on nitrite content of human saliva: Possible relevance to in vivo formation of N-nitroso compounds. Food and Cosmetics Toxicology, 14(6), 545–548.

    Article  CAS  PubMed  Google Scholar 

  52. Olave, N., Nicola, T., Zhang, W., et al. (2012). Transforming growth factor-beta regulates endothelin-1 signaling in the newborn mouse lung during hypoxia exposure. American Journal of Physiology. Lung Cellular and Molecular Physiology, 302(9), L857–L865. doi:10.1152/ajplung.00258.2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. An, S. J., Boyd, R., Zhu, M., et al. (2007). NADPH oxidase mediates angiotensin II-induced endothelin-1 expression in vascular adventitial fibroblasts. Cardiovascular Research, 75(4), 702–709. S0008-6363(07)00066-1 [pii].

    Article  CAS  PubMed  Google Scholar 

  54. Yamashita, K., Discher, D. J., Hu, J., et al. (2001). Molecular regulation of the endothelin-1 gene by hypoxia. Contributions of hypoxia-inducible factor-1, activator protein-1, GATA-2, AND p300/CBP. The Journal of Biological Chemistry, 276(16), 12645–12653. doi:10.1074/jbc.M011344200.

    Article  CAS  PubMed  Google Scholar 

  55. Kourembanas, S., McQuillan, L. P., Leung, G. K., et al. (1993). Nitric oxide regulates the expression of vasoconstrictors and growth factors by vascular endothelium under both normoxia and hypoxia. The Journal of Clinical Investigation, 92(1), 99–104. doi:10.1172/JCI116604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Giaid, A., Yanagisawa, M., Langleben, D., et al. (1993). Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. The New England Journal of Medicine, 328(24), 1732–1739. doi:10.1056/NEJM199306173282402.

    Article  CAS  PubMed  Google Scholar 

  57. Olson, S., Oeckler, R., Li, X., et al. (2004). Angiotensin II stimulates nitric oxide production in pulmonary artery endothelium via the type 2 receptor. American Journal of Physiology. Lung Cellular and Molecular Physiology, 287(3), L559–L568. doi:10.1152/ajplung.00312.2003.

    Article  CAS  PubMed  Google Scholar 

  58. Olson, S. C., Dowds, T. A., Pino, P. A., et al. (1997). ANG II stimulates endothelial nitric oxide synthase expression in bovine pulmonary artery endothelium. The American Journal of Physiology, 273(2 Pt 1), L315–L321.

    CAS  PubMed  Google Scholar 

  59. Mollnau, H., Wendt, M., Szocs, K., et al. (2002). Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide/cGMP signaling. Circulation Research, 90(4), E58–E65.

    Article  PubMed  Google Scholar 

  60. Kim, D., Rybalkin, S. D., Pi, X., et al. (2001). Upregulation of phosphodiesterase 1A1 expression is associated with the development of nitrate tolerance. Circulation, 104(19), 2338–2343.

    Article  CAS  PubMed  Google Scholar 

  61. Patel, D., Alhawaj, R., Kelly, M. R., et al. (2016). Potential role of mitochondrial superoxide decreasing ferrochelatase and heme in coronary artery soluble guanylate cyclase depletion by angiotensin II. American Journal of Physiology. Heart and Circulatory Physiology, 310(11), H1439–H1447. doi:10.1152/ajpheart.00859.2015.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Patel, D., Kelly, M. R., Accarino, J. J. O., et al. (2016). Pulmonary arteries show differences in the effects of angiotensin II stimulation of mitochondrial superoxide on regulation of heme biosynthesis and soluble guanylate cyclase expression. The FASEB Journal, 30(1 Supplement), 774.9.

    Google Scholar 

  63. Patel, D., Alhawaj, R., Kelly, M., et al. (2015). Aminolevulinic acid treatment of pulmonary arteries attenuates endothelin-1 and angiotensin II elicited increases in mitochondrial, but not extra-mitochondrial superoxide. The FASEB Journal, 29(1 Suppl), 957.5.

    Google Scholar 

  64. Ghofrani, H. A., & Grimminger, F. (2009). Soluble guanylate cyclase stimulation: An emerging option in pulmonary hypertension therapy. European Respiratory Review, 18(111), 35–41. doi:10.1183/09059180.00011112.

    Article  CAS  PubMed  Google Scholar 

  65. Dasgupta, A., Bowman, L., D'Arsigny, C. L., et al. (2015). Soluble guanylate cyclase: A new therapeutic target for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Clinical Pharmacology and Therapeutics, 97(1), 88–102. doi:10.1002/cpt.10.

    Article  CAS  PubMed  Google Scholar 

  66. McLaughlin, V. V., Archer, S. L., Badesch, D. B., et al. (2009). ACCF/AHA 2009 expert consensus document on pulmonary hypertension: A report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: Developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation, 119(16), 2250–2294. doi:10.1161/CIRCULATIONAHA.109.192230.

    Article  PubMed  Google Scholar 

  67. Patel, D., Kandhi, S., Kelly, M., et al. (2014). Dehydroepiandrosterone promotes pulmonary artery relaxation by NADPH oxidation-elicited subunit dimerization of protein kinase G 1alpha. American Journal of Physiology. Lung Cellular and Molecular Physiology, 306(4), L383–L391. doi:10.1152/ajplung.00301.2013.

    Article  CAS  PubMed  Google Scholar 

  68. Dumas de La Roque, E., Savineau, J. P., Metivier, A. C., et al. (2012). Dehydroepiandrosterone (DHEA) improves pulmonary hypertension in chronic obstructive pulmonary disease (COPD): A pilot study. Annales d'endocrinologie, 73(1), 20–25. doi:10.1016/j.ando.2011.12.005.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Recent studies from our lab have been funded by NIH grants R01HL115124 and R01HL129797.

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  1. Department of Physiology, New York Medical College, Basic Science Building Rm 604, Valhalla, NY, 10595, USA

    Dhara Patel, Anand Lakhkar & Michael S. Wolin Ph.D.

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  1. Dhara Patel
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Correspondence to Michael S. Wolin Ph.D. .

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  1. Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA

    Yong-Xiao Wang

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Patel, D., Lakhkar, A., Wolin, M.S. (2017). Redox Mechanisms Influencing cGMP Signaling in Pulmonary Vascular Physiology and Pathophysiology. In: Wang, YX. (eds) Pulmonary Vasculature Redox Signaling in Health and Disease. Advances in Experimental Medicine and Biology, vol 967. Springer, Cham. https://doi.org/10.1007/978-3-319-63245-2_13

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