Key result
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.
Why the study?
H2S donors are cardioprotective when given concurrent with ischemia, but their utility in ameliorating remodeling when delayed until 2 h post-infarction in CSE-/- and WT mice was unknown.
Does the H2S donor GYY4137 improve post-infarct remodeling and cardiac function in wild-type and CSE knockout mice?
Does the H2S donor GYY4137 improve post-infarct remodeling and cardiac function in wild-type and CSE knockout mice?
Delayed administration of the H2S donor GYY4137 post-myocardial infarction preserves cardiac function and attenuates adverse remodeling in both wild-type and CSE-deficient mice.
Should not yet change post-MI practice; hypothesis-generating for H2S donation in remodeling.
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.
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Ellmers et al. (2020) studied Myocardial infarction. GYY4137 (slow-release H2S donor) vs. Control (implied) was evaluated on Cardiac function and expression of genes associated with cardiac remodeling. 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.
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