Next Article in Journal
Early Cellular Responses Induced by Sedimentary Calcite-Processed Particles in Bright Yellow 2 Tobacco Cultured Cells
Previous Article in Journal
Regulation of Actin Filament Length by Muscle Isoforms of Tropomyosin and Cofilin
Article

Hydrogen Sulfide Treatment Improves Post-Infarct Remodeling and Long-Term Cardiac Function in CSE Knockout and Wild-Type Mice

1
Christchurch Heart Institute, Department of Medicine, University of Otago, Christchurch 8140, New Zealand
2
Laboratory of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan
3
Department of Pharmacology, National University of Singapore, Singapore 119228, Singapore
4
Inflammation Research Group, Department of Pathology and Biomedical Science, University of Otago, Christchurch 8140, New Zealand
5
Cardiovascular Research Institute, National University of Singapore, Singapore 119228, Singapore
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(12), 4284; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124284
Received: 14 May 2020 / Revised: 10 June 2020 / Accepted: 12 June 2020 / Published: 16 June 2020
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Hydrogen sulfide (H2S) is recognized as an endogenous gaseous signaling molecule generated by cystathionine γ-lyase (CSE) in cardiovascular tissues. H2S up-regulation has been shown to reduce ischemic injury, and H2S donors are cardioprotective in rodent models when administered concurrent with myocardial ischemia. We evaluated the potential utility of H2S therapy in ameliorating cardiac remodeling with administration delayed until 2 h post-infarction in mice with or without cystathionine γ-lyase gene deletion (CSE−/−). The slow-release H2S donor, GYY4137, was administered from 2 h after surgery and daily for 28 days following myocardial infarction (MI) induced by coronary artery ligation, comparing responses in CSE−/− with wild-type (WT) mice (n = 5–10/group/genotype). Measures of cardiac function and expression of key genes associated with cardiac hypertrophy, fibrosis, and apoptosis were documented in atria, ventricle, and kidney tissues. Post-MI GYY4137 administration reduced infarct area and restored cardiac function, accompanied by reduction of the elevated ventricular expression of genes mediating cardiac remodeling to near-normal levels. Few differences between WT and CSE−/− mice were observed, except CSE−/− mice had higher blood pressures, and higher atrial Mir21a expression across all treatment groups. These findings suggest endogenous CSE gene deletion does not substantially exacerbate the long-term response to MI. Moreover, the H2S donor GYY4137 administered after onset of MI preserves cardiac function and protects against adverse cardiac remodeling in both WT and CSE-deficient mice. View Full-Text
Keywords: hydrogen sulfide; myocardial infarction; knockout mice; gene expression hydrogen sulfide; myocardial infarction; knockout mice; gene expression
Show Figures

Graphical abstract

MDPI and ACS Style

Ellmers, L.J.; Templeton, E.M.; Pilbrow, A.P.; Frampton, C.; Ishii, I.; Moore, P.K.; Bhatia, M.; Richards, A.M.; Cameron, V.A. Hydrogen Sulfide Treatment Improves Post-Infarct Remodeling and Long-Term Cardiac Function in CSE Knockout and Wild-Type Mice. Int. J. Mol. Sci. 2020, 21, 4284. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124284

AMA Style

Ellmers LJ, Templeton EM, Pilbrow AP, Frampton C, Ishii I, Moore PK, Bhatia M, Richards AM, Cameron VA. Hydrogen Sulfide Treatment Improves Post-Infarct Remodeling and Long-Term Cardiac Function in CSE Knockout and Wild-Type Mice. International Journal of Molecular Sciences. 2020; 21(12):4284. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124284

Chicago/Turabian Style

Ellmers, Leigh J., Evelyn M. Templeton, Anna P. Pilbrow, Chris Frampton, Isao Ishii, Philip K. Moore, Madhav Bhatia, A. M. Richards, and Vicky A. Cameron. 2020. "Hydrogen Sulfide Treatment Improves Post-Infarct Remodeling and Long-Term Cardiac Function in CSE Knockout and Wild-Type Mice" International Journal of Molecular Sciences 21, no. 12: 4284. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124284

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop