Abstract | BACKGROUND:
Hydrogen sulfide (H2S) has been shown to induce angiogenesis in in vitro models and to promote vessel growth in the setting of hindlimb ischemia. The goal of the present study was to determine the therapeutic potential of a stable, long-acting H2S donor, diallyl trisulfide, in a model of pressure-overload heart failure and to assess the effects of chronic H2S therapy on myocardial vascular density and angiogenesis. METHODS AND RESULTS: Transverse aortic constriction was performed in mice (C57BL/6J; 8-10 weeks of age). Mice received either vehicle or diallyl trisulfide (200 µg/kg) starting 24 hours after transverse aortic constriction and were followed up for 12 weeks using echocardiography. H2S therapy with diallyl trisulfide improved left ventricular remodeling and preserved left ventricular function in the setting of transverse aortic constriction. H2S therapy increased the expression of the proangiogenic factor, vascular endothelial cell growth factor, and decreased the angiogenesis inhibitor, angiostatin. Further studies revealed that H2S therapy increased the expression of the proliferation marker, Ki67, as well as increased the phosphorylation of endothelial NO synthase and the bioavailability of NO. Importantly, these changes were associated with an increase in vascular density within the H2S-treated hearts. CONCLUSIONS:
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Authors | David Polhemus, Kazuhisa Kondo, Shashi Bhushan, Shyamal C Bir, Christopher G Kevil, Toyoaki Murohara, David J Lefer, John W Calvert |
Journal | Circulation. Heart failure
(Circ Heart Fail)
Vol. 6
Issue 5
Pg. 1077-86
(Sep 01 2013)
ISSN: 1941-3297 [Electronic] United States |
PMID | 23811964
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Allyl Compounds
- Ki-67 Antigen
- Sulfides
- Vascular Endothelial Growth Factor A
- vascular endothelial growth factor A, mouse
- diallyl trisulfide
- Nitric Oxide
- Angiostatins
- Nitric Oxide Synthase Type III
- Nos3 protein, mouse
- Hydrogen Sulfide
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Topics |
- Allyl Compounds
(metabolism, pharmacology)
- Angiostatins
(metabolism)
- Animals
- Disease Models, Animal
- Fibrosis
- Heart Failure
(diagnostic imaging, drug therapy, metabolism, physiopathology)
- Hydrogen Sulfide
(metabolism, pharmacology)
- Ki-67 Antigen
(metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- Myocardium
(metabolism, pathology)
- Neovascularization, Physiologic
(drug effects)
- Nitric Oxide
(metabolism)
- Nitric Oxide Synthase Type III
(metabolism)
- Phosphorylation
- Sulfides
(metabolism, pharmacology)
- Time Factors
- Ultrasonography
- Vascular Endothelial Growth Factor A
(metabolism)
- Ventricular Dysfunction, Left
(diagnostic imaging, metabolism, physiopathology, prevention & control)
- Ventricular Function, Left
(drug effects)
- Ventricular Remodeling
(drug effects)
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