Impairment of Endogenous H2S Pathway due to Aging and Endothelium Denudation in Mouse Isolated Thoracic Aorta

. 2025 Mar 21 ; 74 (1) : 59-68.

Jazyk angličtina Země Česko Médium print

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid40116551

Hydrogen sulfide (H2S) is a gas neurotransmitter that is synthesized in various mammalian tissues including vascular tissues and regulates vascular tone. The aim of this study is to investigate whether the endogenous L-cysteine/H2S pathway is impaired due to aging and endothelial denudation in mouse isolated thoracic aorta. For this purpose, young (3-4 months) and old (23-25 months) mice were used in the experiments. The effects of aging and endothelium on endogenous and exogenous H2S-induced vasorelaxation were investigated by cumulative L-cysteine-(1 microM-10 mM) and NaHS-(1 microM-3 mM) induced vasorelaxations, respectively. The L-cysteine-induced relaxations were reduced in old mice aorta compared to the young mice. Also, vasorelaxant responses to L-cysteine (1 microM-10 mM) were reduced on aorta rings with denuded-endothelium of young and old mice. However, the relaxation responses to NaHS were not altered by age or endothelium denudation. The loss of staining of CSE in the endothelial layer was observed in old thoracic aorta. Ach-induced (1-30 microM) relaxation almost abolished in endothelium-denuded rings from both mice group. Also, relaxation Ach reduced in intact endothelium tissue of old mice aorta. In conclusion, the vasorelaxant responses to L-cysteine but not NaHS decreased and the protein expression of CSE reduced in old thoracic aorta rings consistent with a decrease in H2S concentration with aging and endothelium damage, suggesting that aging may be lead to decrease in enzyme expression and H2S signaling system due to endothelium damage in mouse thoracic aorta. Key words Aging, Hydrogen sulfide, L-cysteine, Endothelium, Thoracic aorta.

Zobrazit více v PubMed

Abe K, Kimura H. The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci. 1996;16:1066–1071. doi: 10.1523/JNEUROSCI.16-03-01066.1996. PubMed DOI PMC

Wang R. Two’s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter? FASEB J. 2002;16:1792–1798. doi: 10.1096/fj.02-0211hyp. PubMed DOI

Kimura H. Hydrogen sulfide: its production, release and functions. Amino Acids. 2011;41:113–121. doi: 10.1007/s00726-010-0510-x. PubMed DOI

Shibuya N, Mikami Y, Kimura Y, Nagahara N, Kimura H. Vascular endothelium expresses 3-mercaptopyruvate sulfurtransferase and produces hydrogen sulfide. J Biochem. 2009;146:623–626. doi: 10.1093/jb/mvp111. PubMed DOI

d’Emmanuele di Villa Bianca R, Sorrentino R, Coletta C. Hydrogen sulfide-induced dual vascular effect involves arachidonic acid cascade in rat mesenteric arterial bed. J Pharmacol Exp Ther. 2011;337:59–64. doi: 10.1124/jpet.110.176016. PubMed DOI

Zhao W, Zhang J, Lu Y, Wang R. The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener. EMBO J. 2001;20:6008–6016. doi: 10.1093/emboj/20.21.6008. PubMed DOI PMC

Lüscher TF, Tanner FC, Noll Tschudi M. Endothelial dysfunction in coronary artery disease. Annu Rev Med. 1993;44:395–418. doi: 10.1146/annurev.me.44.020193.002143. PubMed DOI

Inoue T, Saniabadi AR, Matsunaga R, Hoshi K, Yaguchi I, Morooka S. Impaired endothelium-dependent acetylcholine-induced coronary artery relaxation in patients with high serum remnant lipoprotein particles. Atherosclerosis. 1998;139:363–367. doi: 10.1016/S0021-9150(98)00098-7. PubMed DOI

Mombouli JV, Vanhoutte PM. Endothelial dysfunction: from physiology to therapy. J Mol Cell Cardiol. 1999;31:61–74. doi: 10.1006/jmcc.1998.0844. PubMed DOI

Endemann DH, Schiffrin EL. Endothelial dysfunction. J Am Soc Nephrol. 2004;15:1983–1992. doi: 10.1097/01.ASN.0000132474.50966.DA. PubMed DOI

Miao Y, Zhang S, Liang Z, Wang Y, Tian D, Jin S, Guo Q, et al. Hydrogen sulfide ameliorates endothelial dysfunction in aging arteries by regulating ferroptosis. Nitric Oxide. 2023;140–141:77–90. doi: 10.1016/j.niox.2023.10.002. PubMed DOI

Szlęzak D, Hutsch T, Ufnal M, Wróbel M. Heart and kidney H2S production is reduced in hypertensive and older rats. Biochimie. 2022;199:130–138. doi: 10.1016/j.biochi.2022.04.013. PubMed DOI

Zhao W, Wang R. H(2)S-induced vasorelaxation and underlying cellular and molecular mechanisms. Am J Physiol Heart Circ Physiol. 2002;283:H474–H480. doi: 10.1152/ajpheart.00013.2002. PubMed DOI

Predmore BL, Alendy MJ, Ahmed KI, Leeuwenburgh C, Julian D. The hydrogen sulfide signaling system: changes during aging and the benefits of caloric restriction. Age. 2010;32:467–481. doi: 10.1007/s11357-010-9150-z. PubMed DOI PMC

Zhong G, Chen F, Cheng Y, Tang C, Du J. The role of hydrogen sulfide generation in the pathogenesis of hypertension in rats induced by inhibition of nitric oxide synthase. J Hypertens. 2003;21:1879–1885. doi: 10.1097/00004872-200310000-00015. PubMed DOI

Yan H, Du J, Tang C. The possible role of hydrogen sulfide on the pathogenesis of spontaneous hypertension in rats. Biochem Biophys Res Commun. 2004;313:22–27. doi: 10.1016/j.bbrc.2003.11.081. PubMed DOI

Pearson RJ, Wilson T, Wang R. Endogenous hydrogen sulfide and the cardiovascular system-what’s the smell all about? Clin Invest Med. 2006;29:146–150. PubMed

O’Sullivan SE. What is the significance of vascular hydrogen sulphide (H2S)? Br J Pharmacol. 2006;149:609–610. doi: 10.1038/sj.bjp.0706907. PubMed DOI PMC

Yang G, Wu L, Jiang B, Yang W, Qi J, Cao K, Meng Q, et al. H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. Science. 2008;322:587–590. doi: 10.1126/science.1162667. PubMed DOI PMC

Kutz JL, Greaney JL, Santhanam L, Alexander LM. Evidence for a functional vasodilatatory role for hydrogen sulphide in the human cutaneous microvasculature. J Physiol. 2015;593:2121–2129. doi: 10.1113/JP270054. PubMed DOI PMC

Hosoki R, Matsuki N, Kimura H. The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem Biophys Res Commun. 1997;237:527–531. doi: 10.1006/bbrc.1997.6878. PubMed DOI

Kimura H. Hydrogen sulfide induces cyclic AMP and modulates the NMDA receptor. Biochem Biophys Res Commun. 2000;267:129–133. doi: 10.1006/bbrc.1999.1915. PubMed DOI

Zhang NN, Xu HY, Liu XN, Chen YF, Xia CM, Wu XZ, Lu N. The Inhibitory Role of Hydrogen Sulfide in UII-Induced Cardiovascular Effects and the Underlying Signaling Pathways. Antioxidants (Basel) 2022;11:2253. doi: 10.3390/antiox11112253. PubMed DOI PMC

Mani S, Li H, Untereiner A, Wu L, Yang G, Austin RC, Dickhout JG, et al. Decreased endogenous production of hydrogen sulfide accelerates atherosclerosis. Circulation. 2013;127:2523–2534. doi: 10.1161/CIRCULATIONAHA.113.002208. PubMed DOI

Cheng Y, Ndisang JF, Tang G, Cao K, Wang R. Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats. Am J Physiol Heart Circ Physiol. 2004;287:H2316–H2323. doi: 10.1152/ajpheart.00331.2004. PubMed DOI

Hosoki R, Matsuki N, Kimura H. The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem Biophys Res Commun. 1997;237:527–531. doi: 10.1006/bbrc.1997.6878. PubMed DOI

Zhao W, Wang R. H(2)S-induced vasorelaxation and underlying cellular and molecular mechanisms. Am J Physiol Heart Circ Physiol. 2002;283:H474–H480. doi: 10.1152/ajpheart.00013.2002. PubMed DOI

Zhao W, Zhang J, Lu Y, Wang R. The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener. EMBO J. 2001;20:6008–6016. doi: 10.1093/emboj/20.21.6008. PubMed DOI PMC

Roth L, Dogan S, Tuna BG, Aranyi T, Benitez S, Borrell-Pages M, Bozaykut P, et al. Pharmacological modulation of vascular ageing: A review from VascAgeNet. Ageing Res Rev. 2023;92:102122. doi: 10.1016/j.arr.2023.102122. PubMed DOI

Testai L, Citi V, Martelli A, Brogi S, Calderone V. Role of hydrogen sulfide in cardiovascular ageing. Pharmacol Res. 2020;160:105125. doi: 10.1016/j.phrs.2020.105125. PubMed DOI

Smimmo M, Casale V, Casillo GM, Mitidieri E, d’Emmanuele di Villa Bianca R, Bello I, Schettino A, et al. Hydrogen sulfide dysfunction in metabolic syndrome-associated vascular complications involves cGMP regulation through soluble guanylyl cyclase persulfidation. Biomed Pharmacother. 2024;174:116466. doi: 10.1016/j.biopha.2024.116466. PubMed DOI

Yetik-Anacak G, Sevin G, Ozzayım O, Dereli MV, Ahmed A. Hydrogen sulfide: A novel mechanism for the vascular protection by resveratrol under oxidative stress in mouse aorta. Vascul Pharmacol. 2016;87:76–82. doi: 10.1016/j.vph.2016.08.003. PubMed DOI

Fukuda T, Kuroda T, Kono M, Miyamoto T, Tanaka M, Matsui T. Attenuation of L-Type Ca2+ Channel Expression and Vasomotor Response in the Aorta with Age in Both Wistar-Kyoto and Spontaneously Hypertensive Rats. PLoS One. 2014;9:e88975. doi: 10.1371/journal.pone.0088975. PubMed DOI PMC

Kubo S, Doe I, Kurokawa Y, Nishikawa H, Kawabata A. Direct inhibition of endothelial nitric oxide synthase by hydrogen sulfide: Contribution to dual modulation of vascular tension. Toxicology. 2007;232:138–146. doi: 10.1016/j.tox.2006.12.023. PubMed DOI

Nicholson CJ, Xing Y, Lee S, Liang S, Mohan S, O’Rourke C, Kang J, Morgan KG. Ageing causes an aortic contractile dysfunction phenotype. J Cell Mol Med. 2022;26:1456–1465. doi: 10.1111/jcmm.17118. PubMed DOI PMC

Zhu J, Wang Y, Rivett A, Li H, Wu L, Wang R, Yang G. Deficiency of cystathionine gamma-lyase promotes aortic elastolysis and medial degeneration in aged mice. J Mol Cell Cardiol. 2022;171:30–44. doi: 10.1016/j.yjmcc.2022.06.011. PubMed DOI

Kubo S, Doe I, Kurokawa Y, Nishikawa H, Kawabata A. Direct inhibition of endothelial nitric oxide synthase by hydrogen sulfide: contribution to dual modulation of vascular tension. Toxicology. 2007;232:138–146. doi: 10.1016/j.tox.2006.12.023. PubMed DOI

Boulanger CM, Morrison KJ, Vanhoutte PM. Mediation by M3-muscarinic receptors of both endothelium-dependent contraction and relaxation to acetylcholine in the aorta of the spontaneously hypertensive rat. Br J Pharmacol. 1994;112:519–524. doi: 10.1111/j.1476-5381.1994.tb13104.x. PubMed DOI PMC

Gericke A, Sniatecki JJ, Mayer VG, Goloborodko E, Patzak A, Wess J, Pfeiffer N. Role of M1, M3, and M5 muscarinic acetylcholine receptors in cholinergic dilation of small arteries studied with gene-targeted mice. Am J Physiol Heart Circ Physiol. 2011;300:H1602–H1608. doi: 10.1152/ajpheart.00982.2010. PubMed DOI PMC

Zou Q, Leung SW, Vanhoutte PM. Activation of nicotinic receptors can contribute to endothelium-dependent relaxations to acetylcholine in the rat aorta. J Pharmacol Exp Ther. 2012;341:756–763. doi: 10.1124/jpet.112.192229. PubMed DOI

Koga T, Takata Y, Kobayashi K, Takishita S, Yamashita Y, Fujishima M. Ageing suppresses endothelium-dependent relaxation and generates contraction mediated by the muscarinic receptors in vascular smooth muscle of normotensive Wistar-Kyoto and spontaneously hypertensive rats. J Hypertens Suppl. 1988;6:S243–S245. doi: 10.1097/00004872-198812040-00073. PubMed DOI

Mustafa AK, Sikka G, Gazi SK, Steppan J, Jung SM, Bhunia AK, Barodka VM, et al. Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels. Circ Res. 2011;109:1259–1268. doi: 10.1161/CIRCRESAHA.111.240242. PubMed DOI PMC

Mitidieri E, Gurgone D, Caiazzo E, Tramontano T, Cicala C, Sorrentino R, d’Emmanuele di Villa Bianca R. L-cysteine/cystathionine-β-synthase-induced relaxation in mouse aorta involves a L-serine/sphingosine-1-phosphate/NO pathway. Br J Pharmacol. 2020;177:734–744. doi: 10.1111/bph.14654. PubMed DOI PMC

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...