Endogenous Hydrogen Sulfide Regulates Pulmonary Artery Collagen                Remodeling in Rats with High Pulmonary Blood Flow

Li, Xiaohui; Huang, Jin; Geng, Bin; Wang, Li; Tang, Chaoshu; Du, Junbao

doi:10.3181/0807-rm-230

Cited by 25 publications

(16 citation statements)

References 28 publications

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“…Our results revealed for the first time that H 2 S also markedly prevents the development of cardiac fibrosis, decreasing the collagen content in the cardiac tissue, yet the detailed signaling pathway mechanism was not yet elucidated. Li et al (27) reported that H 2 S may reduce collagen accumulation in the pulmonary artery through increasing its degradation by regulating matrix metalloproteinase (MMPs) and metalloproteinase (TIMPs) activities. This needs to be confirmed in future studies on hypertrophied ventricle.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide attenuates cardiac hypertrophy and fibrosis induced by abdominal aortic coarctation in rats

Huang

Wang

Zheng

et al. 2012

Molecular Medicine Reports

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Hydrogen sulfide (H2S) has been recently found to be an endogenous signaling gasotransmitter. Cardiac hypertrophy often develops in the course of heart failure. It is unknown whether or not endogenous H2S protects cardiac hypertrophy. This study was conducted to examine the effects of H2S on cardiac hypertrophy and fibrosis induced by abdominal aortic coarctation and to explore its mechanisms. Male Sprague-Dawley rats were randomly divided into five groups: normal, sham, abdominal aortic coarctation (AAC), AAC treated with enalapril and AAC treated with H2S. One week after surgery, enalapril and sodium hydrosulfide (NaHS)-treated rats were fed for 28 consecutive days and sacrificed. After that, the left ventricle mass index (LVMI), cardiomyocyte size and areas, collagen volume fraction (CVF) of the rats were measured. In the AAC rats, the LVMI, the cardiomyocyte size and areas, and the CVF were all markedly increased while in the H2S groups they were significantly reduced. H2S decreased the levels of Ang-II in the heart, but not in plasma. In addition, H2S also improved the expression of connexin 43 (Cx43). Our results suggest that H2S can significantly suppress cardiac hypertrophy and fibrosis induced by overloaded pressure, possibly by inhibiting the activity of intracardiac Ang-II and by modifying expression of Cx43.

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Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide attenuates cardiac hypertrophy and fibrosis induced by abdominal aortic coarctation in rats

Huang

Wang

Zheng

et al. 2012

Molecular Medicine Reports

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“…MMP-9 activity was suppressed in CBS−/+ mice treated with NaHS (Figure 3). Others have suggested that endogenous H 2 S may decrease the level of MMP-13 and TIMP-1 in rats (Li et al, 2009). The increased MMP-2,-9 protein, mRNA levels and MMP-9 activity caused degradation of matrix proteins and increased BBB permeability.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide mitigates matrix metalloproteinase-9 activity and neurovascular permeability in hyperhomocysteinemic mice

Tyagi

Givvimani

Qipshidze

et al. 2010

Neurochemistry International

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An elevated level of homocysteine (Hcy), known as hyperhomocysteinmia (HHcy), was associated with neurovascular diseases. At physiological levels, hydrogen sulfide (H 2 S) protected the neurovascular system. Because Hcy was also a precursor of hydrogen sulfide (H 2 S), we sought to test whether the H 2 S protected the brain during HHcy. Cystathionine-β-synthase heterozygous (CBS+/−) and wild type (WT) mice were supplemented with or without NaHS (30 µM/L, H 2 S donor) in drinking water. Blood flow and cerebral microvascular permeability in pial vessels were measured by intravital microscopy in WT, WT+NaHS, CBS−/+ and CBS−/+ + NaHS treated mice. The brain tissues were analyzed for matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) by Western blot and RT-PCR. The mRNA levels of CBS and cystathionine gamma lyase (CSE, enzyme responsible for conversion of Hcy to H 2 S) genes were measured by RT-PCR. The results showed a significant increase in MMP-2, MMP-9, TIMP-3 protein and mRNA in CBS (−/+) mice, while H 2 S treatment mitigated this increase. Interstitial localization of MMPs was also apparent through Immunohistochemistry. A decrease in protein and mRNA expression of TIMP-4 was observed in CBS (−/+) mice. Microscopy data revealed increase in permeability in CBS (−/+) mice. These effects were ameliorated by H 2 S and suggested that physiological levels of H 2 S supplementation may have therapeutic potential against HHcyinduced microvascular permeability, in part, by normalizing the MMP/TIMP ratio in the brain. KeywordsBlood Brain Barrier; Tissue inhibitors of matrix metalloproteinases; Cysthathionine-β-synthase (CBS) and Cysthathionine-γ-lyase (CSE)

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“…For instance, endogenous H 2 S prevented pulmonary collagen remodeling induced by high pulmonary blood flow (Li et al, 2009). In addition, downregulation of the endogenous H 2 S pathway in lungs was shown to induce structural remodeling of pulmonary vasculature (Xiaohui et al, 2005).…”

Section: S and Lung Remodeling In Hibernationmentioning

confidence: 99%

The role of endogenous H2S formation in reversible remodeling of lung tissue during hibernation in the Syrian hamster

Talaei

Bouma

Hylkema

et al. 2012

Journal of Experimental Biology

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SUMMARYDuring hibernation, small mammals alternate between periods of metabolic suppression and low body temperature (ʻtorporʼ) and periods of full metabolic recovery with euthermic temperatures (ʻarousalʼ). Previously, we demonstrated marked structural remodeling of the lung during torpor, which is rapidly reversed during arousal. We also found that cooling of hamster cells increased endogenous production of H 2 S through the enzyme cystathionine--synthase (CBS). H 2 S suppresses the immune response and increases deposition of collagen. Therefore, we examined inflammatory markers and matrix metalloproteinase (MMP) activity in relation to CBS expression and H 2 S levels in lungs of euthermic and hibernating Syrian hamsters. Lung remodeling during torpor was confirmed by a strong increase in both collagenous and non-collagenous hydroxyproline content. The number of leukocytes in lung was unchanged in any phase of hibernation, while adhesion molecules VCAM-1 and ICAM-1, and the inflammatory marker NF-B (P65) were modestly upregulated in torpor. Gelatinase activity was decreased in lungs from torpid animals, indicating inhibition of the Zn 2+ -dependent MMP-2 and MMP-9. Moreover, expression of CBS and tissue levels of H 2 S were increased in torpor. All changes normalized during arousal. Inhibition of gelatinase activity in torpor is likely caused by quenching of Zn 2+ by the sulphide ion of H 2 S. In accord, inhibition of CBS normalized gelatinase activity in torpid animals. Conversely, NaHS decreased the gelatinase activity of euthermic animals, which was attenuated by excess Zn 2+. Similar results were obtained on the activity of the Zn 2+ -dependent angiotensin converting enzyme. Our data indicate that increased production of H 2 S through CBS in hamster lungs during torpor contributes to remodeling by inhibition of gelatinase activity and possibly by suppression of the inflammatory response. Although administration of H 2 S is known to induce metabolic suppression in nonhibernating mammals (ʻsuspended animationʼ), this is the first report implying endogenous H 2 S production in natural hibernation.

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Endogenous Hydrogen Sulfide Regulates Pulmonary Artery Collagen Remodeling in Rats with High Pulmonary Blood Flow

Cited by 25 publications

References 28 publications

Hydrogen sulfide attenuates cardiac hypertrophy and fibrosis induced by abdominal aortic coarctation in rats

Hydrogen sulfide attenuates cardiac hypertrophy and fibrosis induced by abdominal aortic coarctation in rats

Hydrogen sulfide mitigates matrix metalloproteinase-9 activity and neurovascular permeability in hyperhomocysteinemic mice

The role of endogenous H2S formation in reversible remodeling of lung tissue during hibernation in the Syrian hamster

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