High glucose induces the release of endothelin-1 through the inhibition of hydrogen sulfide production in HUVECs

  • Authors:
    • Qingbo Guan
    • Wen Liu
    • Yuantao Liu
    • Youfei Fan
    • Xiaolei Wang
    • Chunxiao Yu
    • Yuan Zhang
    • Shunke Wang
    • Jia Liu
    • Jiajun Zhao
    • Ling Gao
  • View Affiliations

  • Published online on: December 31, 2014     https://doi.org/10.3892/ijmm.2014.2059
  • Pages: 810-814
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Hydrogen sulfide (H2S) has recently been identified as an endogenous gaseous signaling molecule. In the vascular system, the formation of H2S is catalyzed by cystathionine γ‑lyase (CSE). Previous studies have demonstrated the protective effects of H2S on ischemic injury in various types of tissue. However,, little is known about the role of H2S in diabetes-associated vascular diseases. Thus, the aim of the present study was to examine the possible role of H2S in high glucose-induced vascular dysfunction, and to explore the underlying mechanisms. Human umbilical vein endothelial cells (HUVECs) were isolated from human umbilical veins. The levels of H2S following treatment with various levels of glucose were determined and the secretion of endothelin-1 (ET-1) was measured by ELISA. The mRNA and protein expression of CSE in the HUVECs was determined by real-time RT-PCR and western blot analysis, respectively. Treatment with high glucose (25 mmol/l) for 48 h significantly increased the secretion of ET-1 by HUVECs, with the concomitant suppression of H2S production and CSE protein expression. The increase in exogenous H2S levels through the administration of sodium hydrosulfide (NaHS) attenuated the high glucose-induced downregulation of CSE protein expression, and significantly inhibited the secretion of ET-1. These results suggest that the downregulation of CSE protein expression and the subsequent decrease in H2S production play a role in high glucose-induced vascular dysfunction possibly by increasing the secretion of ET-1 by endothelial cells.

Introduction

Vascular diseases involving atherosclerosis are the major chronic complications of diabetes mellitus (DM) and the primary prognostic determinants of diabetic patients. It has been estimated that 75% of all deaths among diabetic patients are caused by cardiovascular complications (1). The mechanisms underlying diabetic vascular injuries, however, remain unclear.

Endothelial dysfunction, defined as an imbalance of endothelium-derived vasoconstrictor and vasodilator substances, precedes and dominates the pathogenesis and progression of both macro- and microvascular complications associated with diabetes (2). Nitric oxide (NO) is one of the most well characterized vasodilators, and is also the first gaseous molecule identified as a smooth muscle relaxer (3). Following the discovery of NO, carbon monoxide (CO) was found to have similar functions (4,5). Hydrogen sulfide (H2S) was the third endogeneous gasotransmitter idendified following NO and CO (6). H2S was first discovered in the brain as an endogenous neuromodulator (7,8). Shortly after, it was found that H2S is also present in the endothelium and plays an important role in the regulation of vascular tone (9). To date, 3 enzymes that produce H2S have been identified: cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfur transferase (3MST). Both CBS and 3MST are predominantly expressed in the brain, whereas CSE is primarily localized in the vascular system (6,10). Numerous studies have demonstrated that H2S is able to relax blood vessels and lower blood pressure by opening adenosine triphosphate (ATP)-sensitive potassium (K+) channels in vascular smooth muscle (9,1113). In a previous study, the targeted deletion of the CSE gene in mice markedly reduced H2S levels in serum and these mice had elevated blood pressure and reduced endothelium-dependent vasorelaxation (14). Moreover, H2S has been shown to exert cytoprotective effects against ischemic injury in various animal models of acute ischemia (1519).

Recently, there has been evidence suggesting that H2S metabolism is dysregulated in diabetes. In non-obese diabetic (NOD) mice, it has been reported that endogenous H2S production in the vascular system is significantly impaired, and that this is associated with marked endothelial dysfunction (20). Similarly, it has been shown that plasma H2S levels are markedly reduced in diabetic patients (21). Hyperglycemia is the hallmark of diabetes and has been recognized as an initiator of diabetic endothelial dysfunction. In the present study, the effects of high glucose on the production of H2S in human umbilical vein endothelial cells (HUVECs) were investigated. Furthermore, the effects of H2S on the secretion of endothelin-1 (ET-1) by HUVECs were also determined. The aim of the present study was to address the role and mechanisms of action of H2S in endothelial dysfunction and vascular complications associated with diabetes.

Materials and methods

Cell culture

Human umbilical cords were collected from healthy full-term pregnant mothers during delivery, following the approval of the Shandong University Research Ethics Committee (Jinan, China). Signed informed consent was provided by all donors. The umbilical cords were collected from the Department of Obstetrics, Shandong Provincial Hospital from March to December 2010.

HUVECs were isolated from human umbilical veins and were identified by their cobblestone morphology under a microscope (Zeiss Axioplan; Zeiss, Weimar, Germany) and the strong positive immunoreactivity to von Willebrand factor (data not shown). The cells were grown in 5% CO2 at 37°C in M199 medium (HyClone, Logan, UT, USA) containing 10% fetal bovine serum (FBS; Gibco, Waltham, MA, USA), penicillin (100 U/ml), streptomycin (100 U/ml), L-glutamine and 20 ng/ml vascular endothelial growth factor (VEGF). For all the experiments, cells of passage 2–3 were used. When the cells were 80% confluent, they were grown in medium containing 2% FBS and treated with various concentrations of glucose. To maintain an equal osmotic pressure, 24.5 mmol/l D-mannitol was used to adjust the osmotic concentration.

Measurement of H2S

The levels of H2S were measured as previously described (22,23). Briefly, the cells were collected in 500 μl ice-cold 100 mmol/l potassium phosphate buffer (pH 7.4) and homogenized. The assay mixture containing homogenized cell lysates (430 μl), L-cysteine (10 mmol/l; 20 μl), pyridoxal 5′-phosphate (2 mmol/l, 20 μl) and phosphate-buffered saline (PBS; 30 μl) was incubated at 37°C for 30 min in tightly sealed Eppendorf vials. Zinc acetate [1% (w/v), 250 μl] was then injected to trap the generated H2S followed by trichloroacetic acid (TCA) [10% (w/v), 250 μl] to precipitate the protein and thus terminate the reaction. Subsequently, N,N-dimethyl-p-phenylenediamine sulfate (NNDPD) (20 mmol/l; 133 μl) in 7.2 mol/l hydrochloric acid (HCl) was added followed by FeCl3 (30 mmol/l; 133 μl) in 1.2 mol/l HCl and the absorbance (670 nm) of the aliquots of the resulting solution was determined. The H2S concentration of each sample was calculated against a calibration curve of sodium hydrosulfide (NaHS; 0–250 μmol/l) and expressed as nanomoles of H2S per milligram soluble protein.

Assay for the secretion of ET-1

The HUVECs were seeded in 60-mm cell dishes at 3×105 cells/ml, followed by treatment with various concentrations of glucose. Cell supernatants were collected and the content of ET-1 was detected by ELISA (R&D Systems, Minneapolis, MN, USA). The results were normalized to the cellular protein content in all experiments.

Real-time RT-PCR for CSE

Total RNA was isolated using TRIzol reagent (Takara Bio, Beijing, China) from the treated cells. For real-time RT-PCR, 160 ng template was used in a 10-μl reaction containing 8 pmol of each primer pair and 10 μl of SYBR-Green Premix Ex TaqII (Takara Bio). Reactions were performed using the following cycling conditions: 95°C for 15 sec, followed by 40 cycles of 95°C for 10 sec, 60°C for 20 sec and 72°C for 20 sec. The value of each sample was calculated and expressed as the cycle threshold. The amount of gene expression for each sample was calculated as the difference (ΔCT) between the CT value of the target gene and the CT value of the endogenous control (β-actin). Relative expression was calculated as the difference (ΔΔCT) between the ΔCT values of the test and the control samples for the target gene. The relative level of expression was measured as 2−ΔΔCT. The human primers used were as follows: CSE, forward, CAC TGTCCACCACGTTCAAG and reverse, GTGGCTGCTAA ACCTGAAGC; β-actin, forward, ACAGAGCCTCGCCTT TGCCG and reverse, ACATGCCGGAGCCGTTGTCG.

Western blot analysis for CSE

The cells were homogenized in RIPA lysis buffer with 1% proteinase inhibitor, phenylmethylsulfonyl fluoride (PMSF solution). The protein concentration was measured using the Bradford method. A total of 40 μg of total protein was separated on 10% SDS-PAGE and transferred onto nitrocellulose membranes. The blots were blocked in 5% BSA in TBST solution (10 mM Tris-HCl, pH 7.4, 150 mM NaCl, 0.1% Tween-20) for 30 min at room temperature, followed by incubation for 1 h at room temperature in 1% BSA in TBST solution containing monoclonal anti-CSE antibody (1:4,000, Cat. no. H00001434-M01; Abnova, Taipei, Taiwan). Following incubation with horseradish peroxidase-conjugated secondary antibodies (1:5,000, Cat. no. DkxMu-003-DHRPX), the membranes were washed and developed using an enhanced chemiluminescence kit. Anti-β-actin was routinely blotted and used as a protein loading control. The quantification of band intensity upon western blot analysis was conducted using NIH Image software (ProteinSimple, Santa Clara, CA, USA).

Statistical analysis

All data are presented as the means ± standard deviation (SD). Statistical analysis was performed using one-way ANOVA. The Student-Newman-Keuls test was used for comparisons between groups. A value of P<0.05 was considered to indicate a statistically significant difference.

Results

High glucose reduces the production of H2S in HUVECs

The effects of high glucose on the production of H2S in HUVECs were investigated. As shown in Fig. 1, treatment with high glucose concentrations (25 mmol/l) for 48 h significantly reduced the production of H2S compared with treatment with low glucose (5.5 mmol/l).

High glucose suppresses the expression of CSE in HUVECs

To elucidate the mechanisms responsible for the inhibition of H2S production by high glucose, further experiments were conducted to determine the effects of high glucose on the expression of CSE. As shown in Fig. 2B, treatment of the HUVECs with high glucose (25 mmol/l) did not significantly alter the CSE mRNA levels compared to treatment with low glucose (5 mmol/l). By contrast, compared to treatment with 5.5 mmol/l glucose, treatment with 25 mmol/l glucose significantly inhibited the CSE protein expression in a time-dependent manner (Fig. 2A and C).

Exogenous H2S inhibits the high glucose-induced secretion of ET-1 by HUVECs

As shown in Fig. 3, treatment with 25 mmol/l glucose significantly increased the level of ET-1 following 24 and 48 h of treatment. Pre-treatment for 30 min with 50 μmol/l NaHS inhibited the high glucose-induced secretion of ET-1 at each time point.

Effects of NaHS on CSE protein expression in HUVECs

To determine whether NaHS has an effect on CSE expression, the HUVECs were cultured in 5.5 mmol/l or 25 mmol/l glucose, and treated with 50 or 100 μmol/l NaHS for 48 h. The CSE protein levels were then determined by western blot analysis. As shown in Fig. 4, treatment with 25 mmol/l glucose for 48 h significantly reduced CSE protein expression. This response was significantly attenuated by NaHS at both concentrations examined (50 and 100 μmol/l). However, NaHS at these concentrations showed no evident effect on the basal CSE protein expression in the cells cultured under normal glucose conditions (5.5 mmol/l).

Discussion

As a novel gasotransmitter, H2S has been demonstrated to play important roles in the pathophysiology of several biological systems. In particular, H2S has been investigated extensively in the cardiovascular system. The association between H2S and hypertension was firstly investigated in a study on hypertensive rats (24). In that study, the authors demonstrated that in the hypertensive rats, the level of endogenous H2S was reduced and that exogenous H2S effectively prevented the development of hypertension (24). In the nervous system, H2S has been demonstrated to protect neurons from apoptosis by increasing the production of the antioxidant, glutathione, thus reducing the toxic effects induced by glutamic acid (25). In addition, H2S has been shown to play important roles in the digestive system (26,27) and the respiratory system (2830). To date, little is known however about the role of H2S in diabetes-associated vascular complications. In the present study, the effects of high glucose on the production of H2S in HUVECs were investigated, as well as the effects of exogenous H2S on the secretion of ET-1.

A previous study demonstrated that a decrease in the plasma levels of H2S correlated with coronary heart disease (CHD) risk factors, such as smoking, hypertension and high blood glucose levels (31). The direct association between H2S and high blood glucose levels, however, remains unclear. In the present study, treatment with high glucose reduced the production of H2S in the HUVECs. In the vascular system, CSE is the primary enzyme responsible for H2S production (6). To investigate the mechanisms through which high glucose reduces the production of H2S, CSE protein expression and mRNA levels were analyzed by western blot analysis and real-time RT-PCR, respectively in the current model. The results revealed that high glucose significantly reduced CSE protein expression in the HUVECs, whereas the CSE mRNA expression was not affected. The precise mechanisms involved however are unclear and require further investigation.

ET-1 is one of the most potent endogenous vasoconstrictors released by endothelial cells (32). The balance between NO and ET-1 plays an essential role in the maintenance of vascular tone. It is known that the effects of ET-1 are mediated by a G-protein coupled receptor (33). In response to various endothelial injuries, the release of ET-1 is increased. Consequently, the level of ET-1 is recognized as an indicator of endothelial dysfunction (34). In addition, it has been shown that ET-1 expression is upregulated by high blood glucose levels (35,36). In accordance with the above observations, the present study demonstrated that high glucose increased thee secretion of ET-1 from primary HUVECs.

In the present study, the high glucose-induced secretion of ET-1 coincided with the reduced CSE protein expression and the reduced generation of H2S. Therefore, the effects of H2S on the release of ET-1 in HUVEcs were investigated. NaHS is a widely used source of exogenous H2S. When dissolved in solution, NaHS rapidly dissociates to Na+ and HS. Following this, HS associates with H+ to produce H2S (37). Our results demonstrated that NaHS, as a donor of exogenous H2S, significantly inhibited the high glucose-induced release of ET-1 by HUVECs, consistent with the results of previous studies (38,39). Taken together, these data suggest that H2S may be an upstream regulator of ET-1. In addition to direct conversion into H2S, it has been suggested that NaHS may also indirectly influence the endogenous generation of H2S. In guinea pigs with allergic rhinitis (AR), NaHS was shown to increase CSE expression and H2S production (40). In cultured rat vascular smooth muscle cells, methylglyoxal (MG), an intermediate of glucose metabolism, decreased cellular H2S levels by downregulating CSE protein expression (41). At the same time, NaHS prevented the reduction in CSE protein expression by reducing the cellular MG levels (41). In the present study, NaHS prevented the high glucose-induced downregulation of CSE expression, but did not affect CSE protein expression under normal glucose conditions. These results suggest that NaHS may indirectly influence the production of H2S by regulating CSE protein expression in a high glucose environment.

In conclusion, the results of the present study suggest that the induction of ET-1 secretion by high glucose may be partially mediated through the downregulation of CSE protein expression and thereby, the reduction of the production of H2S. This study also raises the possibility of the use of NaHS as a potential therapeutic agent for diabetic vascular complications. Additional studies are required to confirm these findings in vivo.

Acknowledgments

The present study was supported by the National Natural Science Foundation of China (30971408).

References

1 

Grundy SM, Howard B, Smith S Jr, Eckel R, Redberg R and Bonow RO: Prevention Conference VI: Diabetes and Cardiovascular Disease: executive summary: conference proceeding for healthcare professionals from a special writing group of the American Heart Association. Circulation. 105:2231–2239. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Guangda X and Yuhua W: Apolipoprotein e4 allele and endothelium-dependent arterial dilation in Type 2 diabetes mellitus without angiopathy. Diabetologia. 46:514–519. 2003.PubMed/NCBI

3 

Lüscher TF and Vanhoutte PM: The Endothelium: Modulator of Cardiovascular Function. CRC Press; Boca Raton, FL: pp. 1–228. 1990

4 

Kharitonov VG, Sharma VS, Pilz RB, Magde D and Koesling D: Basis of guanylate cyclase activation by carbon monoxide. Proc Natl Acad Sci USA. 92:2568–2571. 1995. View Article : Google Scholar : PubMed/NCBI

5 

Yet SF, Tian R, Layne MD, et al: Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice. Circ Res. 89:168–173. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Wang R: Two’s company, three’s a crowd: can H S be the third endogenous gaseous transmitter? FASEB J. 16:17922–1798. 2002. View Article : Google Scholar

7 

Warenycia MW, Goodwin LR, Benishin CG, et al: Acute hydrogen sulfide poisoning. Demonstration of selective uptake of sulfide by the brainstem by measurement of brain sulfide levels. Biochem Pharmacol. 38:973–981. 1989. View Article : Google Scholar : PubMed/NCBI

8 

Abe K and Kimura H: The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci. 16:1066–1071. 1996.PubMed/NCBI

9 

Hosoki R, Matsuki N and Kimura H: The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem Biophys Res Commun. 237:527–531. 1997. View Article : Google Scholar : PubMed/NCBI

10 

Shibuya N, Tanaka M, Yoshida M, et al: 3-Mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain. Antioxid Redox Signal. 11:703–714. 2009. View Article : Google Scholar

11 

Zhao W, Zhang J, Lu Y and Wang R: The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener. EMBO J. 20:6008–6016. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Cheng Y, Ndisang JF, Tang G, Cao K and Wang R: Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats. Am J Physiol Heart Circ Physiol. 287:H2316–H2323. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Zhao W and Wang R: H2S-induced vasorelaxation and underlying cellular and molecular mechanisms. Am J Physiol Heart Circ Physiol. 283:H474–H480. 2002.PubMed/NCBI

14 

Yang G, Wu L, Jiang B, et al: H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gammalyase. Science. 322:587–590. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Johansen D, Ytrehus K and Baxter GF: Exogenous hydrogen sulfide (H2S) protects against regional myocardial ischemia-reperfusion injury - Evidence for a role of K ATP channels. Basic Res Cardiol. 101:53–60. 2006. View Article : Google Scholar

16 

Kimura H, Nagai Y, Umemura K and Kimura Y: Physiological roles of hydrogen sulfide: synaptic modulation, neuroprotection, and smooth muscle relaxation. Antioxid Redox Signal. 7:795–803. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Jha S, Calvert JW, Duranski MR, Ramachandran A and Lefer DJ: Hydrogen sulfide attenuates hepatic ischemia-reperfusion injury: role of antioxidant and antiapoptotic signaling. Am J Physiol Heart Circ Physiol. 295:H801–H806. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Tripatara P, Patel NS, Collino M, et al: Generation of endogenous hydrogen sulfide by cystathionine gamma-lyase limits renal ischemia/reperfusion injury and dysfunction. Lab Invest. 88:1038–1048. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Fu Z, Liu X, Geng B, Fang L and Tang C: Hydrogen sulfide protects rat lung from ischemia-reperfusion injury. Life Sci. 82:1196–1202. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Brancaleone V, Roviezzo F, Vellecco V, De Gruttola L, Bucci M and Cirino G: Biosynthesis of H2S is impaired in non-obese diabetic (NOD) mice. Br J Pharmacol. 155:673–680. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Whiteman M, Gooding KM, Whatmore JL, et al: Adiposity is a major determinant of plasma levels of the novel vasodilator hydrogen sulphide. Diabetologia. 53:1722–1726. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Li L, Bhatia M, Zhu YZ, et al: Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse. FASEB. 19:1196–1198. 2005.

23 

Lee M, Schwab C, Yu S, McGeer E and McGeer PL: Astrocytes produce the antiinflammatory and neuroprotective agent hydrogen sulfide. Neurobiol Aging. 30:1523–1534. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Zhong G, Chen F, Cheng Y, Tang C and Du J: The role of hydrogen sulfide generation in the pathogenesis of hypertension in rats induced by inhibition of nitric oxide synthase. J Hypertens. 21:1879–1885. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Kimura Y and Kimura H: Hydrogen sulfide protects neurons from oxidative stress. FASEB J. 18:1165–1167. 2004.PubMed/NCBI

26 

Perini R, Fiorucci S and Wallace JL: Mechanisms of nonsteroidal anti-inflammatory drug-induced gastrointestinal injury and repair: a window of opportunity for cyclooxygenase-inhibiting nitric oxide donors. Can J Gastroenterol. 18:229–236. 2004.PubMed/NCBI

27 

Fiorucci S, Antonelli E, Distrutti E, et al: Inhibition of hydrogen sulfide generation contributes to gastric injury caused by anti-inflammatory nonsteroidal drugs. Gastroenterology. 129:1210–1224. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Li T, Zhao B, Wang C, et al: Regulatory effects of hydrogen sulfide on IL-6, IL-8 and IL-10 levels in the plasma and pulmonary tissue of rats with acute lung injury. Exp Biol Med. 233:1081–1087. 2008. View Article : Google Scholar

29 

Fang L, Li H, Tang C, Geng B, Qi Y and Liu X: Hydrogen sulfide attenuates the pathogenesis of pulmonary fibrosis induced by bleomycin in rats. Can J Physiol Pharmacol. 87:531–538. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Chen YH, Yao WZ, Geng B, et al: Endogenous hydrogen sulfide in patients with COPD. Chest. 128:3205–3211. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Jiang HL, Wu HC, Li ZL, Geng B and Tang CS: Changes of the new gaseous transmitter H S in patients with coronary heart disease. Di Yi Jun Yi Da Xue Xue Bao. 25:951–954. 2005.In Chinese. PubMed/NCBI

32 

Chester AH: Endothelin-1 and the aortic valve. Curr Vasc Pharmacol. 3:353–357. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Yanagisawa M, Kurihara H, Kimura S, et al: A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 332:411–415. 1988. View Article : Google Scholar : PubMed/NCBI

34 

Quiñones MJ and Nicholas SB: Insulin resistance and the endothelium. Curr Diab Rep. 5:246–253. 2005. View Article : Google Scholar : PubMed/NCBI

35 

DeLoach S, Huan Y, Daskalakis C and Falkner B: Endothelin-1 response to glucose and insulin among African Americans. J Am Soc Hypertens. 4:227–235. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Liu J, Wei S, Tian L, Yan L, Guo Q and Ma X: Effects of endomorphins on human umbilical vein endothelial cells under high glucose. Peptides. 32:86–92. 2011. View Article : Google Scholar

37 

Beauchamp RO Jr, Bus JS, Popp JA, Boreiko CJ and Andjelkovich DA: A critical review of the literature on hydrogen sulfide toxicity. Crit Rev Toxicol. 13:25–97. 1984. View Article : Google Scholar : PubMed/NCBI

38 

Li XH, Du JB and Tang CS: Impact of hydrogen sulfide donor on pulmonary vascular structure and vasoactive peptides in rats with pulmonary hypertension induced by high pulmonary blood flow. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 28:159–163. 2006.In Chinese. PubMed/NCBI

39 

Li X, Du J, Jin H, Geng B and Tang C: Sodium hydrosulfide alleviates pulmonary artery collagen remodeling in rats with high pulmonary blood flow. Heart Vessels. 23:409–419. 2008. View Article : Google Scholar : PubMed/NCBI

40 

Shaoqing Y, Ruxin Z, Yinjian C, Jianqiu C, Zhiqiang Y and Genhong L: Down-regulation of endogenous hydrogen sulphide pathway in nasal mucosa of allergic rhinitis in guinea pigs. Allergol Immunopathol. 37:180–187. 2009. View Article : Google Scholar

41 

Chang T, Untereiner A, Liu J and Wu L: Interaction of methylglyoxal and hydrogen sulfide in rat vascular smooth muscle cells. Antioxid Redox Signal. 12:1093–1100. 2010. View Article : Google Scholar

Related Articles

Journal Cover

March-2015
Volume 35 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Guan Q, Liu W, Liu Y, Fan Y, Wang X, Yu C, Zhang Y, Wang S, Liu J, Zhao J, Zhao J, et al: High glucose induces the release of endothelin-1 through the inhibition of hydrogen sulfide production in HUVECs. Int J Mol Med 35: 810-814, 2015
APA
Guan, Q., Liu, W., Liu, Y., Fan, Y., Wang, X., Yu, C. ... Gao, L. (2015). High glucose induces the release of endothelin-1 through the inhibition of hydrogen sulfide production in HUVECs. International Journal of Molecular Medicine, 35, 810-814. https://doi.org/10.3892/ijmm.2014.2059
MLA
Guan, Q., Liu, W., Liu, Y., Fan, Y., Wang, X., Yu, C., Zhang, Y., Wang, S., Liu, J., Zhao, J., Gao, L."High glucose induces the release of endothelin-1 through the inhibition of hydrogen sulfide production in HUVECs". International Journal of Molecular Medicine 35.3 (2015): 810-814.
Chicago
Guan, Q., Liu, W., Liu, Y., Fan, Y., Wang, X., Yu, C., Zhang, Y., Wang, S., Liu, J., Zhao, J., Gao, L."High glucose induces the release of endothelin-1 through the inhibition of hydrogen sulfide production in HUVECs". International Journal of Molecular Medicine 35, no. 3 (2015): 810-814. https://doi.org/10.3892/ijmm.2014.2059