title: Homocysteine to hydrogen sulfide or hypertension.
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 H(2)S, which is a strong antioxidant and vasorelaxation factor. At an elevated level, homocysteine inactivates proteins by homocysteinylation including its endogenous metabolizing enzyme, cystathionine gamma-lyase. Thus, reduced production of H(2)S 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 H(2)S to ameliorate hypertension.
authors.affiliation: Department of Physiology & Biophysics, University of Louisville School of Medicine, 500 South Preston Street, Louisville, KY 40202, USA. u0sen001@louisville.edu
authors.forename: Utpal
authors.initials: U
authors.lastname: Sen
authors.forename: Paras K
authors.initials: PK
authors.lastname: Mishra
authors.forename: Neetu
authors.initials: N
authors.lastname: Tyagi
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Tyagi
mesh_terms: D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D020138:Hyperhomocysteinemia / Q000150:complications / Q000378:metabolism; D006973:Hypertension / Q000209:etiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism
chemical_list: D006710:Homocysteine; D009569:Nitric Oxide; D003094:Collagen; D002118:Calcium; D006862:Hydrogen Sulfide
references.citation: Can J Physiol Pharmacol. 1999 Dec;77(12):950-7
references.pmid: 10606441
references.citation: Antioxid Redox Signal. 2007 Nov;9(11):1899-909
references.pmid: 17822370
references.citation: Hepatology. 2008 Feb;47(2):659-67
references.pmid: 18098324
references.citation: N Engl J Med. 1985 Sep 19;313(12):709-15
references.pmid: 4033695
references.citation: Am J Pathol. 1969 Jul;56(1):111-28
references.pmid: 5792556
references.citation: Clin Chim Acta. 1983 Jan 7;127(1):105-13
references.pmid: 6825304
references.citation: Biochem Biophys Res Commun. 2006 Jul 7;345(3):938-44
references.pmid: 16707097
references.citation: Int J Cardiol. 1997 Dec 31;62 Suppl 2:S85-90
references.pmid: 9488199
references.citation: J Am Coll Cardiol. 1999 Dec;34(7):2002-6
references.pmid: 10588216
references.citation: Semin Thromb Hemost. 2000;26(3):281-9
references.pmid: 11011845
references.citation: Am J Physiol Heart Circ Physiol. 2004 Nov;287(5):H2316-23
references.pmid: 15191893
references.citation: Circulation. 1997 Sep 16;96(6):1745-9
references.pmid: 9323056
references.citation: Am J Physiol. 1998 Feb;274(2):C396-405
references.pmid: 9486129
references.citation: J Clin Invest. 1986 Apr;77(4):1370-6
references.pmid: 3514679
references.citation: J Clin Invest. 1996 Jul 1;98(1):24-9
references.pmid: 8690798
references.citation: J Clin Pharmacol. 2003 Dec;43(12):1299-306
references.pmid: 14615465
references.citation: J Am Coll Nutr. 2001 Oct;20(5 Suppl):428S-435S; discussion 440S-442S
references.pmid: 11603653
references.citation: J Hum Hypertens. 2006 Apr;20(4):267-71
references.pmid: 16437127
references.citation: Circulation. 2001 Jun 5;103(22):2717-23
references.pmid: 11390343
references.citation: J Cell Physiol. 2009 Jul;220(1):257-66
references.pmid: 19308943
references.citation: Cardiovasc Res. 1997 Jun;34(3):597-602
references.pmid: 9231044
references.citation: Clin Exp Hypertens. 1999 Apr;21(3):181-98
references.pmid: 10225475
references.citation: Am J Physiol. 1998 May;274(5):L775-85
references.pmid: 9612293
references.citation: J Neurosci. 1996 Feb 1;16(3):1066-71
references.pmid: 8558235
references.citation: FASEB J. 1999 Dec;13(15):2277-83
references.pmid: 10593875
references.citation: Hypertension. 1997 Oct;30(4):948-52
references.pmid: 9336398
references.citation: J Lipid Res. 1993 Dec;34(12):2051-61
references.pmid: 8301226
references.citation: JAMA. 1995 Nov 15;274(19):1526-33
references.pmid: 7474221
references.citation: Atherosclerosis. 1995 Apr 24;114(2):175-83
references.pmid: 7605386
references.citation: J Biol Chem. 2009 Aug 14;284(33):22457-22466
references.pmid: 19531479
references.citation: BMJ. 2002 Nov 23;325(7374):1202
references.pmid: 12446535
references.citation: Circulation. 1995 Feb 15;91(4):1161-74
references.pmid: 7850955
references.citation: Amino Acids. 2008 May;34(4):573-85
references.pmid: 18071843
references.citation: J Cell Physiol. 2000 Apr;183(1):28-36
references.pmid: 10699963
references.citation: Heart Vessels. 2000;15(3):135-43
references.pmid: 11289502
references.citation: J Biol Chem. 1997 Jul 4;272(27):17012-7
references.pmid: 9202015
references.citation: Atherosclerosis. 1996 May;122(2):201-16
references.pmid: 8769683
references.citation: J Physiol Pharmacol. 2008 Dec;59 Suppl 9:155-67
references.pmid: 19261978
references.citation: Kidney Int. 1999 Mar;55(3):1028-35
references.pmid: 10027940
references.citation: Am J Physiol Heart Circ Physiol. 2005 Dec;289(6):H2649-56
references.pmid: 16085680
references.citation: Ann Intern Med. 2003 Nov 4;139(9):761-76
references.pmid: 14597461
references.citation: Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1596-605
references.pmid: 18556571
references.citation: J Pathol. 2001 Apr;193(4):538-45
references.pmid: 11276015
references.citation: Lancet. 1998 Jan 3;351(9095):36-7
references.pmid: 9433433
references.citation: N Engl J Med. 1997 Apr 17;336(16):1117-24
references.pmid: 9099655
references.citation: Atherosclerosis. 1997 Jul 25;132(2):177-85
references.pmid: 9242963
references.citation: J Thromb Haemost. 2008 Jan;6(1):184-92
references.pmid: 17944991
references.citation: Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6369-73
references.pmid: 8022789
references.citation: Am J Hypertens. 2001 Jul;14(7 Pt 1):627-31
references.pmid: 11465645
references.citation: Arterioscler Thromb Vasc Biol. 1997 Oct;17(10):2074-81
references.pmid: 9351374
references.citation: Hypertension. 1997 Oct;30(4):934-41
references.pmid: 9336396
references.citation: N Engl J Med. 1997 Jul 24;337(4):230-6
references.pmid: 9227928
references.citation: Am J Physiol Cell Physiol. 2006 Mar;290(3):C883-91
references.pmid: 16251475
references.citation: J Hypertens. 2007 Oct;25(10):2100-4
references.pmid: 17885553
references.citation: Acta Neurol Scand. 1992 Nov;86(5):490-5
references.pmid: 1481630
references.citation: Circulation. 1997 Dec 16;96(12):4131-2
references.pmid: 9416877
references.citation: Am J Physiol Renal Physiol. 2009 Aug;297(2):F410-9
references.pmid: 19474193
references.citation: Semin Thromb Hemost. 2000;26(3):291-5
references.pmid: 11011846
references.citation: Physiol Chem Phys. 1975;7(5):401-8
references.pmid: 1197382
references.citation: Clin Chem Lab Med. 2007;45(12):1771-6
references.pmid: 17990952
references.citation: J Mol Cell Cardiol. 1991 Jun;23(6):695-704
references.pmid: 1834855
references.citation: Int J Cardiol. 2001 Jul;79(2-3):277-86
references.pmid: 11461752
references.citation: Am J Reprod Immunol. 2001 Feb;45(2):65-71
references.pmid: 11216876
references.citation: J Clin Invest. 1996 Jan 1;97(1):146-53
references.pmid: 8550827
references.citation: FASEB J. 2004 Mar;18(3):557-9
references.pmid: 14734631
references.citation: Antioxid Redox Signal. 2009 Apr;11(4):703-14
references.pmid: 18855522
references.citation: Am J Physiol. 1992 Mar;262(3 Pt 2):R389-94
references.pmid: 1558209
references.citation: Metabolism. 2002 Aug;51(8):981-8
references.pmid: 12145770
references.citation: Mol Cell Biochem. 1998 Apr;181(1-2):107-16
references.pmid: 9562247
references.citation: Science. 2008 Oct 24;322(5901):587-90
references.pmid: 18948540
references.citation: J Nutr. 1999 May;129(5):928-33
references.pmid: 10222381
references.citation: Atherosclerosis. 2001 Aug;157(2):353-60
references.pmid: 11472734
references.citation: FASEB J. 2002 Nov;16(13):1792-8
references.pmid: 12409322
references.citation: Am J Physiol Cell Physiol. 2008 Jan;294(1):C169-77
references.pmid: 17989210
references.citation: Eur J Pharmacol. 2008 Sep 4;591(1-3):224-30
references.pmid: 18634778
references.citation: EMBO J. 2001 Nov 1;20(21):6008-16
references.pmid: 11689441
references.citation: Drugs. 1992;44 Suppl 1:23-30
references.pmid: 1283581
references.citation: Biochem Biophys Res Commun. 1997 Aug 28;237(3):527-31
references.pmid: 9299397
references.citation: Heart Vessels. 2004 Mar;19(2):75-80
references.pmid: 15042391
references.citation: J Biol Chem. 2004 Nov 19;279(47):49199-205
references.pmid: 15347670
references.citation: Nat Med. 1996 Apr;2(4):386-9
references.pmid: 8597939
references.citation: Nature. 1993 Apr 29;362(6423):801-9
references.pmid: 8479518
references.citation: J Biochem. 2009 Nov;146(5):623-6
references.pmid: 19605461
references.citation: Life Sci. 2006 Feb 16;78(12):1299-309
references.pmid: 16257422