GYY4137 attenuates remodeling, preserves cardiac function and modulates the natriuretic peptide response to ischemia

Shera Lilyanna, Meng Teng Peh, Oi Wah Liew, Peipei Wang, Philip K. Moore, Arthur Mark Richards, Eliana Cecilia Martinez Valencia

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Aims: Myocardial infarction followed by adverse left ventricular (LV) remodeling is the most frequent proximate cause of heart failure. Hydrogen sulfide (H<inf>2</inf>S) is an important endogenous modulator of diverse physiological and pathophysiological processes. Its role in post-ischemic ventricular remodeling and the associated neurohormonal responses has not been defined. Here, we aimed at evaluating whether the slow-releasing water-soluble H<inf>2</inf>S donor GYY4137 (GYY) exerts cardioprotective effects and modulates the neurohormonal response to cardiac ischemic injury. Methods and results: Treatment for 2 or 7days with GYY (100mg/Kg/48h, IP) after acute myocardial infarction (MI) in rats preserved LV dimensions and function in vivo, compared to untreated infarcted (MI), placebo- and dl-propargylglycine- (PAG, an inhibitor of endogenous H<inf>2</inf>S synthesis) treated animals (n=9/group/time-point). LV dimensions and function in GYY-treated animals were comparable to healthy sham-operated rats. GYY-treated hearts had significantly less LV fibrosis than MI, placebo and PAG hearts. A higher density of blood vessels was found in the LV scar area of GYY-treated animals compared to all other infarcted groups. Despite preserved LV structure and function, treatment with GYY increased the levels of the natriuretic peptides ANP and BNP in association with enhanced cyclic GMP levels, paralleled by higher cGMP-dependent protein kinase type I (cGKI) protein levels. Conclusions: Our data suggest that the slow-releasing H<inf>2</inf>S donor, GYY4137, preserves cardiac function, attenuates adverse remodeling and may exert post-ischemic cardioprotective (pro-angiogenic, anti-apoptotic, anti-hypertrophic and anti-fibrotic) effects in part through enhanced early post-ischemic endogenous natriuretic peptide activation.

Original languageEnglish (US)
Pages (from-to)27-37
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume87
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

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Keywords

  • Angiogenesis
  • Hydrogen sulfide
  • Myocardial infarction
  • Natriuretic peptides
  • Remodeling

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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