Role of hydrogen sulfide in portal hypertension and esophagogastric junction vascular disease

Wang, Chao; Han, Juan; Liang, Xiao; Jin, Chang'e; Li, Miaosi; Yang, Zhaohui

doi:10.3748/wjg.v20.i4.1079

Cited by 32 publications

(33 citation statements)

References 18 publications

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“…In patients with grade 2 and 3 hypertension, plasma H 2 S concentrations were found to be lower than in subjects with normal BP (Sun et al ., ). In patients with portal hypertension, endogenous H 2 S levels have been reported to be lower than in healthy controls; and an inverse relationship was seen between disease severity and lower plasma H 2 S levels, the latter being inversely correlated with portal vein diameters and Child‐Pugh score (Wang et al ., ). In patients with pulmonary hypertension (PHT), levels of H 2 S and expression of CSE have been found to be reduced; based on evaluation of the receiver‐operating characteristic curve, CSE had the most significant sensitivity and specificity to predict dynamic PHT (Sun et al ., ).…”

Section: Deficiency Of H2s Production and Hypertension Developmentmentioning

confidence: 97%

Emerging role of hydrogen sulfide in hypertension and related cardiovascular diseases

Meng

Xie

et al. 2014

British J Pharmacology

105

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Hydrogen sulfide (H2S) has traditionally been viewed as a highly toxic gas; however, recent studies have implicated H2S as a third member of the gasotransmitter family, exhibiting properties similar to NO and carbon monoxide. Accumulating evidence has suggested that H2S influences a wide range of physiological and pathological processes, among which blood vessel relaxation, cardioprotection and atherosclerosis have been particularly studied. In the cardiovascular system, H2S production is predominantly catalyzed by cystathionine γ-lyase (CSE). Decreased endogenous H2S levels have been found in hypertensive patients and animals, and CSE −/− mice develop hypertension with age, suggesting that a deficiency in H2S contributes importantly to BP regulation. H2S supplementation attenuates hypertension in different hypertensive animal models. The mechanism by which H2S was originally proposed to attenuate hypertension was by virtue of its action on vascular tone, which may be related to effects on different ion channels. Both H2S and NO cause vasodilatation and there is cross-talk between these two molecules to regulate BP. Suppression of oxidative stress may also contribute to antihypertensive effects of H2S. This review also summarizes the state of research on H2S and hypertension in China. A better understanding of the role of H2S in hypertension and related cardiovascular diseases will allow novel strategies to be devised for their treatment. LINKED ARTICLESThis article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10. 1111/bph.2015.172.issue-23 Abbreviation 2K1C, two-kidney-one-clip; Ang II; angiotensin II; AOA, aminooxyacetic acid; AT1 receptor, angiotensin II type 1 receptor; CBS, cystathionine-β-synthase; CO, carbon monoxide; CSE, cystathionine-γ-lyase; DBP, diastolic BP; eNOS, endothelial NOS; H2S, hydrogen sulfide; I/R, ischaemia/reperfusion; L-NAME, N G -nitro-l-arginine methyl ester; MAP, mean arterial pressure; MPST, 3-mercaptopyruvate sulfurtransferase; MWT, medial wall thickness; PAAT, pulmonary arterial acceleration time; PAG; DL-propargylglycine; PHT, pulmonary hypertension; RVET, right ventricular ejection time; RVH, right ventricular hypertrophy; SBP, systolic BP; SHR, spontaneously hypertensive rat; SMCs, smooth muscle cells; VEGFR-1, soluble fms-like tyrosine kinase 1; VD, vas deferens IntroductionIn recent years, the 'gasotransmitters' NO, carbon monoxide (CO) and hydrogen sulfide (H2S) have been the object of intense research (Papapetropoulos et al., 2014). In the last two decades, NO has been extensively studied; and in more recent times, the importance of H2S in cardiovascular regulation has become increasingly apparent (Polhemus and Lefer, 2014). Until the H2S content within the brain was first measured in postmortem studies in 1989, H2S was traditionally viewed as a highly toxic gas devoid of beneficial biological or physiological functions (Goodwin et al., 1989). Subsequently, H2S quic...

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Section: Deficiency Of H2s Production and Hypertension Developmentmentioning

confidence: 97%

Emerging role of hydrogen sulfide in hypertension and related cardiovascular diseases

Meng

Xie

et al. 2014

British J Pharmacology

105

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“…Moreover, cirrhotic livers lack H 2 S and its generating enzyme cystathionase (CSE) expressed in HSCs. 156,157 Interestingly, exogenous H 2 S reduces portal perfusion pressure and inhibits CCl4-induced hepatic fibrosis. 157,158 FXR is able to stimulate CSE expression.…”

Section: Fxr Ligand Promote H 2 S-mediated Sinusoidal Vasodilationmentioning

confidence: 99%

“…145,159 Notably H 2 S also causes apoptosis of activated HSCs. 147,156,158 However, the activation of CSE might be also comediated rather by G protein-coupled bile acid receptor 1 (GPBAR1) than by FXR, a receptor for secondary bile acids which is coactivated by OCA and likely steroidal FXR agonists. 160,161…”

Section: Fxr Ligand Promote H 2 S-mediated Sinusoidal Vasodilationmentioning

confidence: 99%

Vascular Targets for the Treatment of Portal Hypertension

et al. 2019

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Portal hypertension is the main driver for severe complications in patients with liver cirrhosis. With improved understanding of molecular pathways that promote hepatic vascular remodeling, vasoconstriction, and sinusoidal capillarization potential vascular targets for the treatment of portal hypertension have been identified. Inhibition of vascular endothelial and platelet-derived growth factors–driven angiogenesis has been shown to reduce portal pressure and decrease hepatic inflammation. Angiopoietin/Tie signaling represents additional promising vascular targets in liver disease. The eNOS-NO-sGC-cGMP pathway modulates sinusoidal vasoconstriction and capillarization. Nuclear farnesoid X receptor (FXR) agonists decrease intrahepatic vascular resistance by inhibition of fibrogenesis and sinusoidal remodeling. Statins ameliorate endothelial dysfunction, decrease portal pressure, and reduce fibrogenesis. Anticoagulation with low-molecular heparin or anti-Xa inhibitors improved portal hypertension by deactivation of hepatic stellate cells and potentially via reduction of sinusoidal microthrombosis. This review summarizes important vascular targets for treatment of portal hypertension that have shown promising results in experimental studies.

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“…The deficiency in endogenous CBS/H 2 S or CSE/H 2 S system is responsible for fibrosis [ 8 , 19 ]. Downregulation of CBS and CSE expression/activity and decreased plasma H 2 S levels were observed in patients with hepatocirrhosis [ 20 – 23 ]. And animal models of various organ fibrosis demonstrated the significant decrease of the endogenous H 2 S level in plasma and tissues and the H 2 S-producing enzymes, whereas the administration exogenous H 2 S could inhibit the fibrosis development [ 9 , 13 , 15 , 18 , 19 , 24 , 25 ].…”

Section: Altered Endogenous H 2 S/its Produmentioning

confidence: 99%

“…The metabolic levels of H 2 S and its producing enzymes were observed to change in human hepatic fibrosis and cirrhosis, as well as in animal and cellular models of hepatic fibrosis [ 11 , 13 , 20 , 23 , 38 , 41 ]. In patients with cirrhosis-induced portal hypertension, plasma H 2 S levels were significantly lower than healthy controls and correlated inversely with the disease severity by Child-Pugh score (42.6 ± 4.7 μ mol/L, 33.5 ± 7.7 μ mol/L, and 22.2 ± 7.9 μ mol/L in group Child-Pugh score of A, B, and C, resp., but 43.5 ± 6.2 μ mol/L in control group) [ 20 ]. This decrease stemmed from a reduction of CBS and CSE expression/activity [ 21 – 23 , 42 ].…”

Section: Altered Endogenous H 2 S/its Produmentioning

confidence: 99%

Hydrogen Sulfide as a Potential Therapeutic Target in Fibrosis

Zhang

Pan

Zhou

et al. 2015

Oxidative Medicine and Cellular Longevity

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Hydrogen sulfide (H2S), produced endogenously by the activation of two major H2S-generating enzymes (cystathionine β-synthase and cystathionine γ-lyase), plays important regulatory roles in different physiologic and pathologic conditions. The abnormal metabolism of H2S is associated with fibrosis pathogenesis, causing damage in structure and function of different organs. A number of in vivo and in vitro studies have shown that both endogenous H2S level and the expressions of H2S-generating enzymes in plasma and tissues are significantly downregulated during fibrosis. Supplement with exogenous H2S mitigates the severity of fibrosis in various experimental animal models. The protective role of H2S in the development of fibrosis is primarily attributed to its antioxidation, antiapoptosis, anti-inflammation, proangiogenesis, and inhibition of fibroblasts activities. Future studies might focus on the potential to intervene fibrosis by targeting the pathway of endogenous H2S-producing enzymes and H2S itself.

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Role of hydrogen sulfide in portal hypertension and esophagogastric junction vascular disease

Abstract: H₂S prevents vascular restructuring caused by excessive proliferation of smooth muscle cells via apoptosis induction, which helps to maintain normal vascular structures.

Cited by 32 publications

References 18 publications

Emerging role of hydrogen sulfide in hypertension and related cardiovascular diseases

Emerging role of hydrogen sulfide in hypertension and related cardiovascular diseases

Vascular Targets for the Treatment of Portal Hypertension

Hydrogen Sulfide as a Potential Therapeutic Target in Fibrosis

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