H2S ameliorates oxidative and proteolytic stresses and protects the heart against adverse remodeling in chronic heart failure

Paras Kumar Mishra, Neetu Tyagi, Utpal Sen, Srikanth Givvimani, Suresh C. Tyagi

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Reactive oxygen and nitrogen species (ROS and RNS, respectively) generate nitrotyrosine and activate latent resident myocardial matrix metalloproteinases (MMPs). Although in chronic heart failure (CHF) there is robust increase in ROS, RNS, and MMP activation, recent data suggest that hydrogen sulfide (H 2S, a strong antioxidant gas) is cardioprotective. However, the role of H2S in mitigating oxidative and proteolytic stresses in cardiac remodeling/apoptosis in CHF was unclear. To test the hypothesis that H 2S ameliorated cardiac apoptosis and fibrosis by decreasing oxidative and proteolytic stresses, arteriovenous fistula (AVF) was created in wild-type (C57BL/6J) mice. The hearts were analyzed at 0, 2, and 6 wk after AVF. To reverse the remodeling, AVF mice were treated with NaHS (an H2S donor, 30 μmol/l in drinking water) at 8 and 10 wk. The levels of MMPs were measured by gelatin-gel zymography. The levels of nitrotyrosine, tissue inhibitors of metalloproteinase (TIMPs), β1-integrin, and a disintegrin and metalloproteinase-12 (ADAM-12) were analyzed by Western blots. The levels of pericapillary and interstitial fibrosis were identified by Masson trichrome stains. The levels of apoptosis were measured by identifying the TdT-mediated dUTP nick end labeling (TUNEL)-positive cells and caspase-3 levels. The results suggested robust nitrotyrosine and MMP activation at 2 and 6 wk of AVF. The treatment with H2S donor mitigated nitrotyrosine generation and MMP activation (i.e., oxidative and proteolytic stresses). The levels of TIMP-1 and TIMP-3 were increased and TIMP-4 decreased in AVF hearts. The treatment with H2S donor reversed this change in TIMPs levels. The levels of ADAM-12, apoptosis, and fibrosis were robust and integrin were decreased in AVF hearts. The treatment with H2S donor attenuated the fibrosis, apoptosis, and decrease in integrin.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume298
Issue number2
DOIs
StatePublished - Jan 29 2010
Externally publishedYes

Fingerprint

Arteriovenous Fistula
Matrix Metalloproteinases
Oxidative Stress
Heart Failure
Apoptosis
Fibrosis
Integrins
Disintegrins
Tissue Inhibitor of Metalloproteinase-1
Metalloproteases
Tissue Inhibitor of Metalloproteinase-3
Tissue Inhibitor of Metalloproteinases
Reactive Nitrogen Species
Hydrogen Sulfide
Gelatin
Inbred C57BL Mouse
Caspase 3
Drinking Water
Reactive Oxygen Species
Antioxidants

Keywords

  • ADAM
  • Apoptosis
  • Collagen
  • Extracellular matrix
  • Fibrosis
  • Homocysteine
  • Integrin
  • Left ventricle hypertrophy
  • Matrix metalloproteinase
  • TUNEL
  • Tissue inhibitor of metalloproteinase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

H2S ameliorates oxidative and proteolytic stresses and protects the heart against adverse remodeling in chronic heart failure. / Mishra, Paras Kumar; Tyagi, Neetu; Sen, Utpal; Givvimani, Srikanth; Tyagi, Suresh C.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 298, No. 2, 29.01.2010.

Research output: Contribution to journalArticle

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AU - Tyagi, Suresh C.

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