Skip to main content
SpringerLink
Log in

Homocysteine to Hydrogen Sulfide or Hypertension

  • Review Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Hyperhomocysteinemia, an increased level of plasma homocysteine, is an independent risk factor for the development of premature arterial fibrosis with peripheral and cerebro-vascular, neurogenic and hypertensive heart disease, coronary occlusion and myocardial infarction, as well as venous thromboembolism. It is reported that hyperhomocysteinemia causes vascular dysfunction by two major routes: (1) increasing blood pressure and, (2) impairing the vasorelaxation activity of endothelial-derived nitric oxide. The homocysteine activates metalloproteinases and induces collagen synthesis and causes imbalances of elastin/collagen ratio which compromise vascular elastance. The metabolites from hyperhomocysteinemic endothelium could modify components of the underlying muscle cells, leading to vascular dysfunction and hypertension. Homocysteine metabolizes in the body to produce H2S, which is a strong antioxidant and vasorelaxation factor. At an elevated level, homocysteine inactivates proteins by homocysteinylation including its endogenous metabolizing enzyme, cystathionine γ-lyase. Thus, reduced production of H2S during hyperhomocysteinemia exemplifies hypertension and vascular diseases. In light of the present information, this review focuses on the mechanism of hyperhomocysteinemia-associated hypertension and highlights the novel modulatory role of H2S to ameliorate hypertension.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

AT1:

Angiotensin type 1

CBS:

Cystathionine-β synthase

CSE:

Cystathionine-γ lyase

CTGF:

Connective tissue growth factor

ECM:

Extracellular matrix

H2S:

Hydrogen sulfide

MMP:

Matrix metalloproteinase

NO:

Nitric oxide

NOS:

Nitric oxide synthase

O ●−2 :

Superoxide

ROS:

Reactive oxygen species

TIMP:

Tissue inhibitor of metalloproteinase

VSMC:

Vascular smooth muscle cell

References

  1. Oparil, S., Zaman, M. A., & Calhoun, D. A. (2003). Pathogenesis of hypertension. Annals of Internal Medicine, 139, 761–776.

    CAS  PubMed  Google Scholar 

  2. Rolland, P. H., Friggi, A., Barlatier, A., Piquet, P., Latrille, V., Faye, M. M., et al. (1995). Hyperhomocysteinemia-induced vascular damage in the minipig. Captopril-hydrochlorothiazide combination prevents elastic alterations. Circulation, 91, 1161–1174.

    CAS  PubMed  Google Scholar 

  3. Appel, L. J., Moore, T. J., Obarzanek, E., Vollmer, W. M., Svetkey, L. P., Sacks, F. M., et al. (1997). A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. New England Journal of Medicine, 336, 1117–1124.

    Article  CAS  PubMed  Google Scholar 

  4. Woo, K. S., Chook, P., Lolin, Y. I., Sanderson, J. E., Metreweli, C., & Celermajer, D. S. (1999). Folic acid improves arterial endothelial function in adults with hyperhomocystinemia. Journal of the American College of Cardiology, 34, 2002–2006.

    Article  CAS  PubMed  Google Scholar 

  5. Wollesen, F., Brattstrom, L., Refsum, H., Ueland, P. M., Berglund, L., & Berne, C. (1999). Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus. Kidney International, 55, 1028–1035.

    Article  CAS  PubMed  Google Scholar 

  6. Upchurch, G. R., Jr., Welch, G. N., Fabian, A. J., Freedman, J. E., Johnson, J. L., Keaney, J. F., Jr., et al. (1997). Homocyst(e)ine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase. Journal of Biological Chemistry, 272, 17012–17017.

    Article  CAS  PubMed  Google Scholar 

  7. Dudman, N. P., & Wilcken, D. E. (1983). Increased plasma copper in patients with homocystinuria due to cystathionine beta-synthase deficiency. Clinica Chimica Acta, 127, 105–113.

    Article  CAS  Google Scholar 

  8. Yoshida, Y., Nakano, A., Hamada, R., Kamitsuchibashi, H., Yamamoto, K., Akagi, H., et al. (1992). Patients with homocystinuria: High metal concentrations in hair, blood and urine. Acta Neurologica Scandinavica, 86, 490–495.

    Article  CAS  PubMed  Google Scholar 

  9. Ross, R. (1993). The pathogenesis of atherosclerosis: A perspective for the 1990s. Nature, 362, 801–809.

    Article  CAS  PubMed  Google Scholar 

  10. Lamping, K. G. (1997). Hypercontractility of vascular muscle in atherosclerosis. Circulation, 96, 4131–4132.

    CAS  PubMed  Google Scholar 

  11. Boers, G. H. (2000). Mild hyperhomocysteinemia is an independent risk factor of arterial vascular disease. Seminars in Thrombosis and Hemostasis, 26, 291–295.

    Article  CAS  PubMed  Google Scholar 

  12. Sutton-Tyrrell, K., Bostom, A., Selhub, J., & Zeigler-Johnson, C. (1997). High homocysteine levels are independently related to isolated systolic hypertension in older adults. Circulation, 96, 1745–1749.

    CAS  PubMed  Google Scholar 

  13. Rodrigo, R., Passalacqua, W., Araya, J., Orellana, M., & Rivera, G. (2003). Homocysteine and essential hypertension. Journal of Clinical Pharmacology, 43, 1299–1306.

    Article  CAS  PubMed  Google Scholar 

  14. Lip, G. Y., Edmunds, E., Martin, S. C., Jones, A. F., Blann, A. D., & Beevers, D. G. (2001). A pilot study of homocyst(e)ine levels in essential hypertension: Relationship to von Willebrand factor, an index of endothelial damage. American Journal of Hypertension, 14, 627–631.

    Article  CAS  PubMed  Google Scholar 

  15. Yang, G., Wu, L., Jiang, B., Yang, W., Qi, J., Cao, K., et al. (2008). H2S as a physiologic vasorelaxant: Hypertension in mice with deletion of cystathionine gamma-lyase. Science, 322, 587–590.

    Article  CAS  PubMed  Google Scholar 

  16. Wang, R. (2002). Two’s company, three’s a crowd: Can H2S be the third endogenous gaseous transmitter? The FASEB Journal, 16, 1792–1798.

    Article  CAS  PubMed  Google Scholar 

  17. Shibuya, N., Mikami, Y., Kimura, Y., Nagahara, N., & Kimura, H. (2009). Vascular endothelium expresses 3-mercaptopyruvate sulfurtransferase and produces hydrogen sulfide. Journal of Biochemistry, 146, 623–626.

    Article  CAS  PubMed  Google Scholar 

  18. Shibuya, N., Tanaka, M., Yoshida, M., Ogasawara, Y., Togawa, T., Ishii, K., et al. (2009). 3-Mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain. Antioxidants and Redox Signaling, 11, 703–714.

    Article  CAS  PubMed  Google Scholar 

  19. Abe, K., & Kimura, H. (1996). The possible role of hydrogen sulfide as an endogenous neuromodulator. Journal of Neuroscience, 16, 1066–1071.

    CAS  PubMed  Google Scholar 

  20. Hosoki, R., Matsuki, N., & Kimura, H. (1997). The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochemical and Biophysical Research Communications, 237, 527–531.

    Article  CAS  PubMed  Google Scholar 

  21. Barber, T., Triguero, A., Martinez-Lopez, I., Torres, L., Garcia, C., Miralles, V. J., et al. (1999). Elevated expression of liver gamma-cystathionase is required for the maintenance of lactation in rats. Journal of Nutrition, 129, 928–933.

    CAS  PubMed  Google Scholar 

  22. Zhao, W., Zhang, J., Lu, Y., & Wang, R. (2001). The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener. EMBO Journal, 20, 6008–6016.

    Article  CAS  PubMed  Google Scholar 

  23. Singh, S., Padovani, D., Leslie, R. A., Chiku, T., & Banerjee, R. (2009). Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. Journal of Biological Chemistry, 284, 22457–22466.

    Article  CAS  PubMed  Google Scholar 

  24. Yao, K. (1975). Effects of several unusual sulfur-containing amino acids on rat liver cystathionine-gamma-lyase. Physiological Chemistry and Physics, 7, 401–408.

    CAS  PubMed  Google Scholar 

  25. Chang, L., Geng, B., Yu, F., Zhao, J., Jiang, H., Du, J., et al. (2008). Hydrogen sulfide inhibits myocardial injury induced by homocysteine in rats. Amino Acids, 34, 573–585.

    Article  CAS  PubMed  Google Scholar 

  26. Cheng, Y., Ndisang, J. F., Tang, G., Cao, K., & Wang, R. (2004). Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats. American Journal of Physiology. Heart and Circulatory Physiology, 287, H2316–H2323.

    Article  CAS  PubMed  Google Scholar 

  27. Stabler, S. P., Steegborn, C., Wahl, M. C., Oliveriusova, J., Kraus, J. P., Allen, R. H., et al. (2002). Elevated plasma total homocysteine in severe methionine adenosyltransferase I/III deficiency. Metabolism, 51, 981–988.

    Article  CAS  PubMed  Google Scholar 

  28. Jakubowski, H. (1999). Protein homocysteinylation: Possible mechanism underlying pathological consequences of elevated homocysteine levels. The FASEB Journal, 13, 2277–2283.

    CAS  PubMed  Google Scholar 

  29. McCully, K. S. (1969). Vascular pathology of homocysteinemia: Implications for the pathogenesis of arteriosclerosis. American Journal of Pathology, 56, 111–128.

    CAS  PubMed  Google Scholar 

  30. McCully, K. S. (1996). Homocysteine and vascular disease. Nature Medicine, 2, 386–389.

    Article  CAS  PubMed  Google Scholar 

  31. Tyagi, S. C. (1999). Homocyst(e)ine and heart disease: Pathophysiology of extracellular matrix. Clinical and Experimental Hypertension, 21, 181–198.

    Article  CAS  PubMed  Google Scholar 

  32. Boers, G. H., Smals, A. G., Trijbels, F. J., Fowler, B., Bakkeren, J. A., Schoonderwaldt, H. C., et al. (1985). Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease. New England Journal of Medicine, 313, 709–715.

    CAS  PubMed  Google Scholar 

  33. Wald, D. S., Law, M., & Morris, J. K. (2002). Homocysteine and cardiovascular disease: Evidence on causality from a meta-analysis. BMJ, 325, 1202.

    Article  PubMed  Google Scholar 

  34. Nygard, O., Nordrehaug, J. E., Refsum, H., Ueland, P. M., Farstad, M., & Vollset, S. E. (1997). Plasma homocysteine levels and mortality in patients with coronary artery disease. New England Journal of Medicine, 337, 230–236.

    Article  CAS  PubMed  Google Scholar 

  35. Nygard, O., Vollset, S. E., Refsum, H., Stensvold, I., Tverdal, A., Nordrehaug, J. E., et al. (1995). Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. JAMA, 274, 1526–1533.

    Article  CAS  PubMed  Google Scholar 

  36. Malinow, M. R., Levenson, J., Giral, P., Nieto, F. J., Razavian, M., Segond, P., et al. (1995). Role of blood pressure, uric acid, and hemorheological parameters on plasma homocyst(e)ine concentration. Atherosclerosis, 114, 175–183.

    Article  CAS  PubMed  Google Scholar 

  37. Jakubowski, H. (2008). The pathophysiological hypothesis of homocysteine thiolactone-mediated vascular disease. Journal of Physiology and Pharmacology, 59(Suppl 9), 155–167.

    PubMed  Google Scholar 

  38. Dayal, S., & Lentz, S. R. (2008). Murine models of hyperhomocysteinemia and their vascular phenotypes. Arteriosclerosis, Thrombosis, and Vascular Biology, 28, 1596–1605.

    Article  CAS  PubMed  Google Scholar 

  39. Tyagi, S. C., Smiley, L. M., Mujumdar, V. S., Clonts, B., & Parker, J. L. (1998). Reduction-oxidation (Redox) and vascular tissue level of homocyst(e)ine in human coronary atherosclerotic lesions and role in extracellular matrix remodeling and vascular tone. Molecular and Cellular Biochemistry, 181, 107–116.

    Article  CAS  PubMed  Google Scholar 

  40. Tyagi, S. C., Smiley, L. M., & Mujumdar, V. S. (1999). Homocyst(e)ine impairs endocardial endothelial function. Canadian Journal of Physiology and Pharmacology, 77, 950–957.

    Article  CAS  PubMed  Google Scholar 

  41. Distrutti, E., Mencarelli, A., Santucci, L., Renga, B., Orlandi, S., Donini, A., et al. (2008). The methionine connection: Homocysteine and hydrogen sulfide exert opposite effects on hepatic microcirculation in rats. Hepatology, 47, 659–667.

    Article  CAS  PubMed  Google Scholar 

  42. Chambers, J. C., McGregor, A., Jean-Marie, J., & Kooner, J. S. (1998). Acute hyperhomocysteinaemia and endothelial dysfunction. Lancet, 351, 36–37.

    Article  CAS  PubMed  Google Scholar 

  43. Tsai, J. C., Perrella, M. A., Yoshizumi, M., Hsieh, C. M., Haber, E., Schlegel, R., et al. (1994). Promotion of vascular smooth muscle cell growth by homocysteine: A link to atherosclerosis. Proceedings of the National Academy of Sciences of the United States of America, 91, 6369–6373.

    Article  CAS  PubMed  Google Scholar 

  44. Upchurch, G. R., Jr., Welch, G. N., Fabian, A. J., Pigazzi, A., Keaney, J. F., Jr., & Loscalzo, J. (1997). Stimulation of endothelial nitric oxide production by homocyst(e)ine. Atherosclerosis, 132, 177–185.

    Article  CAS  PubMed  Google Scholar 

  45. Tyagi, N., Gillespie, W., Vacek, J. C., Sen, U., Tyagi, S. C., & Lominadze, D. (2009). Activation of GABA-A receptor ameliorates homocysteine-induced MMP-9 activation by ERK pathway. Journal of Cellular Physiology, 220, 257–266.

    Article  CAS  PubMed  Google Scholar 

  46. Tyagi, N., Sedoris, K. C., Steed, M., Ovechkin, A. V., Moshal, K. S., & Tyagi, S. C. (2005). Mechanisms of homocysteine-induced oxidative stress. American Journal of Physiology. Heart and Circulatory Physiology, 289, H2649–H2656.

    Article  CAS  PubMed  Google Scholar 

  47. Lentz, S. R., Sobey, C. G., Piegors, D. J., Bhopatkar, M. Y., Faraci, F. M., Malinow, M. R., et al. (1996). Vascular dysfunction in monkeys with diet-induced hyperhomocyst(e)inemia. Journal of Clinical Investigation, 98, 24–29.

    Article  CAS  PubMed  Google Scholar 

  48. Miller, A., Mujumdar, V., Shek, E., Guillot, J., Angelo, M., Palmer, L., et al. (2000). Hyperhomocyst(e)inemia induces multiorgan damage. Heart and Vessels, 15, 135–143.

    Article  CAS  PubMed  Google Scholar 

  49. Mujumdar, V. S., Smiley, L. M., & Tyagi, S. C. (2001). Activation of matrix metalloproteinase dilates and decreases cardiac tensile strength. International Journal of Cardiology, 79, 277–286.

    Article  CAS  PubMed  Google Scholar 

  50. Tyagi, S. C. (1998). Homocysteine redox receptor and regulation of extracellular matrix components in vascular cells. American Journal of Physiology, 274, C396–C405.

    CAS  PubMed  Google Scholar 

  51. Tsai, J. C., Wang, H., Perrella, M. A., Yoshizumi, M., Sibinga, N. E., Tan, L. C., et al. (1996). Induction of cyclin A gene expression by homocysteine in vascular smooth muscle cells. Journal of Clinical Investigation, 97, 146–153.

    Article  CAS  PubMed  Google Scholar 

  52. van Guldener, C., & Stehouwer, C. D. (2000). Hyperhomocysteinemia, vascular pathology, and endothelial dysfunction. Seminars in Thrombosis and Hemostasis, 26, 281–289.

    Article  PubMed  Google Scholar 

  53. Yang, G., Cao, K., Wu, L., & Wang, R. (2004). Cystathionine gamma-lyase overexpression inhibits cell proliferation via a H2S-dependent modulation of ERK1/2 phosphorylation and p21Cip/WAK-1. Journal of Biological Chemistry, 279, 49199–49205.

    Article  CAS  PubMed  Google Scholar 

  54. Raziel, A., Kornberg, Y., Friedler, S., Schachter, M., Sela, B. A., & Ron-El, R. (2001). Hypercoagulable thrombophilic defects and hyperhomocysteinemia in patients with recurrent pregnancy loss. American Journal of Reproductive Immunology, 45, 65–71.

    Article  CAS  PubMed  Google Scholar 

  55. Zemel, M. B. (2001). Calcium modulation of hypertension and obesity: Mechanisms and implications. Journal of the American College of Nutrition, 20, 428S–435S. (discussion 440S–442S).

    CAS  PubMed  Google Scholar 

  56. Fleckenstein-Grun, G., Frey, M., Thimm, F., Hofgartner, W., & Fleckenstein, A. (1992). Calcium overload—an important cellular mechanism in hypertension and arteriosclerosis. Drugs, 44(Suppl 1), 23–30.

    Article  PubMed  Google Scholar 

  57. Vijayagopal, P., & Subramaniam, P. (2001). Effect of calcium channel blockers on proteoglycan synthesis by vascular smooth muscle cells and low density lipoprotein–proteoglycan interaction. Atherosclerosis, 157, 353–360.

    Article  CAS  PubMed  Google Scholar 

  58. Schachter, M. (1997). Vascular smooth muscle cell migration, atherosclerosis, and calcium channel blockers. International Journal of Cardiology, 62(Suppl 2), S85–S90.

    Article  PubMed  Google Scholar 

  59. Mujumdar, V. S., Hayden, M. R., & Tyagi, S. C. (2000). Homocyst(e)ine induces calcium second messenger in vascular smooth muscle cells. Journal of Cellular Physiology, 183, 28–36.

    Article  CAS  PubMed  Google Scholar 

  60. Nagai, Y., Tsugane, M., Oka, J., & Kimura, H. (2004). Hydrogen sulfide induces calcium waves in astrocytes. The FASEB Journal, 18, 557–559.

    CAS  PubMed  Google Scholar 

  61. Pan, T. T., Neo, K. L., Hu, L. F., Yong, Q. C., & Bian, J. S. (2008). H2S preconditioning-induced PKC activation regulates intracellular calcium handling in rat cardiomyocytes. American Journal of Physiology. Cell Physiology, 294, C169–C177.

    Article  CAS  PubMed  Google Scholar 

  62. Sen, S., & Young, D. (1991). Effect of sodium deprivation on cardiac hypertrophy in spontaneously hypertensive rats: Influence of aging. Journal of Molecular and Cellular Cardiology, 23, 695–704.

    Article  CAS  PubMed  Google Scholar 

  63. Packer, C. S., Roepke, J. E., Oberlies, N. H., & Rhoades, R. A. (1998). Myosin isoform shifts and decreased reactivity in hypoxia-induced hypertensive pulmonary arterial muscle. American Journal of Physiology, 274, L775–785.

    CAS  PubMed  Google Scholar 

  64. Starkebaum, G., & Harlan, J. M. (1986). Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. Journal of Clinical Investigation, 77, 1370–1376.

    Article  CAS  PubMed  Google Scholar 

  65. Heinecke, J. W., Kawamura, M., Suzuki, L., & Chait, A. (1993). Oxidation of low density lipoprotein by thiols: Superoxide-dependent and -independent mechanisms. Journal of Lipid Research, 34, 2051–2061.

    CAS  PubMed  Google Scholar 

  66. Poddar, R., Sivasubramanian, N., DiBello, P. M., Robinson, K., & Jacobsen, D. W. (2001). Homocysteine induces expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human aortic endothelial cells: Implications for vascular disease. Circulation, 103, 2717–2723.

    CAS  PubMed  Google Scholar 

  67. Bouloumie, A., Bauersachs, J., Linz, W., Scholkens, B. A., Wiemer, G., Fleming, I., et al. (1997). Endothelial dysfunction coincides with an enhanced nitric oxide synthase expression and superoxide anion production. Hypertension, 30, 934–941.

    CAS  PubMed  Google Scholar 

  68. Bosse, H. M., & Bachmann, S. (1997). Immunohistochemically detected protein nitration indicates sites of renal nitric oxide release in Goldblatt hypertension. Hypertension, 30, 948–952.

    CAS  PubMed  Google Scholar 

  69. Du, J., Hui, Y., Cheung, Y., Bin, G., Jiang, H., Chen, X., et al. (2004). The possible role of hydrogen sulfide as a smooth muscle cell proliferation inhibitor in rat cultured cells. Heart and Vessels, 19, 75–80.

    Article  PubMed  Google Scholar 

  70. Jeong, S. O., Pae, H. O., Oh, G. S., Jeong, G. S., Lee, B. S., Lee, S., et al. (2006). Hydrogen sulfide potentiates interleukin-1beta-induced nitric oxide production via enhancement of extracellular signal-regulated kinase activation in rat vascular smooth muscle cells. Biochemical and Biophysical Research Communications, 345, 938–944.

    Article  CAS  PubMed  Google Scholar 

  71. Jovin, I. S., Wolfe, M. L., Gefter, W. B., Miller, W. T., Aronchick, J. M., Flannery, D. T., et al. (1999). Plasma homocysteine levels are not associated with extent of coronary artery calcification in asymptomatic persons. Circulation, 100, 25–25.

    Google Scholar 

  72. Hofmann, M. A., Lu, Y., Ferran, L., Kohl, B., & Schmidt, A. M. (1999). Homocysteine induces vascular activation in vitro and in vivo: Accelerated atherosclerosis develops in apo E null mice with hyperhomocysteinemia. Circulation, 100, 44–44.

    Google Scholar 

  73. Matthias, D., Becker, C. H., Riezler, R., & Kindling, P. H. (1996). Homocysteine induced arteriosclerosis-like alterations of the aorta in normotensive and hypertensive rats following application of high doses of methionine. Atherosclerosis, 122, 201–216.

    Article  CAS  PubMed  Google Scholar 

  74. Majors, A., Ehrhart, L. A., & Pezacka, E. H. (1997). Homocysteine as a risk factor for vascular disease. Enhanced collagen production and accumulation by smooth muscle cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 17, 2074–2081.

    CAS  PubMed  Google Scholar 

  75. Jourdheuil-Rahmani, D., Rolland, P. H., Rosset, E., Branchereau, A., & Garcon, D. (1997). Homocysteine induces synthesis of a serine elastase in arterial smooth muscle cells from multi-organ donors. Cardiovascular Research, 34, 597–602.

    Article  CAS  PubMed  Google Scholar 

  76. Hodgkin, D. D., Gilbert, R. D., Roos, P. J., Sandberg, L. B., & Boucek, R. J. (1992). Dietary lipid modulation of connective tissue matrix in rat abdominal aorta. American Journal of Physiology, 262, R389–394.

    CAS  PubMed  Google Scholar 

  77. Dayal, S., & Lentz, S. R. (2007). Role of redox reactions in the vascular phenotype of hyperhomocysteinemic animals. Antioxidants and Redox Signaling, 9, 1899–1909.

    Article  CAS  PubMed  Google Scholar 

  78. Liu, X., Luo, F., Li, J., Wu, W., Li, L., & Chen, H. (2008). Homocysteine induces connective tissue growth factor expression in vascular smooth muscle cells. Journal of Thrombosis and Haemostasis, 6, 184–192.

    Article  CAS  PubMed  Google Scholar 

  79. Mayer, O., Filipovsky, J., Dolejsova, M., Cifkova, R., Simon, J., & Bolek, L. (2006). Mild hyperhomocysteinaemia is associated with increased aortic stiffness in general population. Journal of Human Hypertension, 20, 267–271.

    Article  CAS  PubMed  Google Scholar 

  80. Hongfang, J., Cong, B., Zhao, B., Zhang, C., Liu, X., Zhou, W., et al. (2006). Effects of hydrogen sulfide on hypoxic pulmonary vascular structural remodeling. Life Sciences, 78, 1299–1309.

    Article  PubMed  CAS  Google Scholar 

  81. Moshal, K. S., Sen, U., Tyagi, N., Henderson, B., Steed, M., Ovechkin, A. V., et al. (2006). Regulation of homocysteine-induced MMP-9 by ERK1/2 pathway. American Journal of Physiology. Cell Physiology, 290, C883–C891.

    Article  CAS  PubMed  Google Scholar 

  82. Corbel, M., Caulet-Maugendre, S., Germain, N., Molet, S., Lagente, V., & Boichot, E. (2001). Inhibition of bleomycin-induced pulmonary fibrosis in mice by the matrix metalloproteinase inhibitor batimastat. Journal of Pathology, 193, 538–545.

    Article  CAS  PubMed  Google Scholar 

  83. Martinez, M. L., Castro, M. M., Rizzi, E., Fernandes, K., Demacq, C., Bendhack, L. M., et al. (2008). Lercanidipine reduces matrix metalloproteinase-2 activity and reverses vascular dysfunction in renovascular hypertensive rats. European Journal of Pharmacology, 591, 224–230.

    Article  CAS  PubMed  Google Scholar 

  84. Sen, U., Basu, P., Abe, O. A., Givvimani, S., Tyagi, N., Metreveli, N., et al. (2009). Hydrogen sulfide ameliorates hyperhomocysteinemia-associated chronic renal failure. American Journal of Physiology. Renal Physiology, 297, F410–F419.

    Article  CAS  PubMed  Google Scholar 

  85. Sen, U., Herrmann, M., Herrmann, W., & Tyagi, S. C. (2007). Synergism between AT1 receptor and hyperhomocysteinemia during vascular remodeling. Clinical Chemistry and Laboratory Medicine, 45, 1771–1776.

    Article  CAS  PubMed  Google Scholar 

  86. Laggner, H., Hermann, M., Esterbauer, H., Muellner, M. K., Exner, M., Gmeiner, B. M., et al. (2007). The novel gaseous vasorelaxant hydrogen sulfide inhibits angiotensin-converting enzyme activity of endothelial cells. Journal of Hypertension, 25, 2100–2104.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported, in part, by the National Institutes of Health grants, HL-74185, HL-71010, HL-88012 and NS-51568.

Disclosures

No competing financial interests exist.

Author information

Authors and Affiliations

  1. Department of Physiology & Biophysics, University of Louisville School of Medicine, 500 South Preston Street, Louisville, KY, 40202, USA

    Utpal Sen, Paras K. Mishra, Neetu Tyagi & Suresh C. Tyagi

Authors
  1. Utpal Sen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paras K. Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Neetu Tyagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Suresh C. Tyagi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Utpal Sen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sen, U., Mishra, P.K., Tyagi, N. et al. Homocysteine to Hydrogen Sulfide or Hypertension. Cell Biochem Biophys 57, 49–58 (2010). https://doi.org/10.1007/s12013-010-9079-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-010-9079-y

Keywords

Search

Navigation