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MPST but not CSE is the primary regulator of hydrogen sulfide production and function in the coronary artery.
Am J Physiol Heart Circ Physiol. 2016 Jan 01; 310(1):H71-9.AJ

Abstract

Hydrogen sulfide (H2S) has emerged as an important gasotransmitter in the vasculature. In this study, we tested the hypothesis that H2S contributes to coronary vasoregulation and evaluated the physiological relevance of two sources of H2S, namely, cystathionine-γ-lyase (CSE) and 3-mercaptypyruvate sulfertransferase (MPST). MPST was detected in human coronary artery endothelial cells as well as rat and mouse coronary artery; CSE was not detected in the coronary vasculature. Rat coronary artery homogenates produced H2S through the MPST pathway but not the CSE pathway in vitro. In vivo coronary vasorelaxation response was similar in CSE knockout mice, wild-type mice (WT), and WT mice treated with the CSE inhibitor propargylglycine, suggesting that CSE-produced H2S does not have a significant role in coronary vasoregulation in vivo. Ex vivo, the MPST substrate 3-mercaptopyruvate (3-MP) and H2S donor sodium hydrosulfide (NaHS) elicited similar coronary vasoreactivity responses. Pyruvate did not have any effects on vasoreactivity. The vasoactive effect of H2S appeared to be nitric oxide (NO) dependent: H2S induced coronary vasoconstriction in the presence of NO and vasorelaxation in its absence. Maximal endothelial-dependent relaxation was intact after 3-MP and NaHS induced an increase in preconstriction tone, suggesting that endothelial NO synthase activity was not significantly inhibited. In vitro, H2S reacted with NO, which may, in part explain the vasoconstrictive effects of 3-MP and NaHS. Taken together, these data show that MPST rather than CSE generates H2S in coronary artery, mediating its effects through direct modulation of NO. This has important implications for H2S-based therapy in healthy and diseased coronary arteries.

Authors+Show Affiliations

Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland;Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Anethesiology and Pain Medicine, Ajou University School of Medicine, Suwon, Korea.Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland;Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland;Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland;Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland;Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland;Department of Medicine (Cardiology), Johns Hopkins University, Baltimore, Maryland; and.Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland;Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland;Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland; LSantha1@jhmi.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26519030

Citation

Kuo, Maggie M., et al. "MPST but Not CSE Is the Primary Regulator of Hydrogen Sulfide Production and Function in the Coronary Artery." American Journal of Physiology. Heart and Circulatory Physiology, vol. 310, no. 1, 2016, pp. H71-9.
Kuo MM, Kim DH, Jandu S, et al. MPST but not CSE is the primary regulator of hydrogen sulfide production and function in the coronary artery. Am J Physiol Heart Circ Physiol. 2016;310(1):H71-9.
Kuo, M. M., Kim, D. H., Jandu, S., Bergman, Y., Tan, S., Wang, H., Pandey, D. R., Abraham, T. P., Shoukas, A. A., Berkowitz, D. E., & Santhanam, L. (2016). MPST but not CSE is the primary regulator of hydrogen sulfide production and function in the coronary artery. American Journal of Physiology. Heart and Circulatory Physiology, 310(1), H71-9. https://doi.org/10.1152/ajpheart.00574.2014
Kuo MM, et al. MPST but Not CSE Is the Primary Regulator of Hydrogen Sulfide Production and Function in the Coronary Artery. Am J Physiol Heart Circ Physiol. 2016 Jan 1;310(1):H71-9. PubMed PMID: 26519030.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MPST but not CSE is the primary regulator of hydrogen sulfide production and function in the coronary artery. AU - Kuo,Maggie M, AU - Kim,Dae Hee, AU - Jandu,Sandeep, AU - Bergman,Yehudit, AU - Tan,Siqi, AU - Wang,Huilei, AU - Pandey,Deepesh R, AU - Abraham,Theodore P, AU - Shoukas,Artin A, AU - Berkowitz,Dan E, AU - Santhanam,Lakshmi, Y1 - 2015/10/30/ PY - 2014/09/10/received PY - 2015/10/08/accepted PY - 2015/11/1/entrez PY - 2015/11/1/pubmed PY - 2016/5/3/medline KW - 3-mercaptopyruvate sulfurtransferase KW - coronary tone KW - coronary vasoregulation KW - cystathionine-γ-lyase KW - hydrogen sulfide SP - H71 EP - 9 JF - American journal of physiology. Heart and circulatory physiology JO - Am J Physiol Heart Circ Physiol VL - 310 IS - 1 N2 - Hydrogen sulfide (H2S) has emerged as an important gasotransmitter in the vasculature. In this study, we tested the hypothesis that H2S contributes to coronary vasoregulation and evaluated the physiological relevance of two sources of H2S, namely, cystathionine-γ-lyase (CSE) and 3-mercaptypyruvate sulfertransferase (MPST). MPST was detected in human coronary artery endothelial cells as well as rat and mouse coronary artery; CSE was not detected in the coronary vasculature. Rat coronary artery homogenates produced H2S through the MPST pathway but not the CSE pathway in vitro. In vivo coronary vasorelaxation response was similar in CSE knockout mice, wild-type mice (WT), and WT mice treated with the CSE inhibitor propargylglycine, suggesting that CSE-produced H2S does not have a significant role in coronary vasoregulation in vivo. Ex vivo, the MPST substrate 3-mercaptopyruvate (3-MP) and H2S donor sodium hydrosulfide (NaHS) elicited similar coronary vasoreactivity responses. Pyruvate did not have any effects on vasoreactivity. The vasoactive effect of H2S appeared to be nitric oxide (NO) dependent: H2S induced coronary vasoconstriction in the presence of NO and vasorelaxation in its absence. Maximal endothelial-dependent relaxation was intact after 3-MP and NaHS induced an increase in preconstriction tone, suggesting that endothelial NO synthase activity was not significantly inhibited. In vitro, H2S reacted with NO, which may, in part explain the vasoconstrictive effects of 3-MP and NaHS. Taken together, these data show that MPST rather than CSE generates H2S in coronary artery, mediating its effects through direct modulation of NO. This has important implications for H2S-based therapy in healthy and diseased coronary arteries. SN - 1522-1539 UR - https://www.unboundmedicine.com/medline/citation/26519030/MPST_but_not_CSE_is_the_primary_regulator_of_hydrogen_sulfide_production_and_function_in_the_coronary_artery_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.00574.2014?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -