Heat shock protein 90 is responsible for hyperdynamic circulation in portal hypertensive rats

Ai, Jian-hua; Yang, Zhen; Qiu, Fa-Zu; Zhu, Tong

doi:10.3748/wjg.v9.i11.2544

Cited by 6 publications

(5 citation statements)

References 32 publications

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“…[27] In the present study, animals subjected to the same experimental model had increased expression of HSP90 when compared with controls (Fig. 1), which demonstrates the influence of this chaperone in the eNOS activation pathway and confirms previous results published by Ai et al, [28] in which HSP90 was overexpressed in the endothelium of mesenteric vessels in PPVL animals. HSP90 in PH exerts an agonist effect on NO production and vasodilation via eNOS.…”

Section: Discussionsupporting

confidence: 91%

Synergistic Antioxidant and Anti-Inflammatory Action of N-Acetylcysteine In Portal Hypertensive Gastropathy in Rats

Marques¹

2022

Hepatology Forum

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Background and Aim: Portal hypertension (PH) is a syndrome associated with cirrhosis and characterized by a progressive increase in portal pressure, with consequent compensatory vascular dilation. Gastric vascular changes associated with oxidative and nitrosative stress characterize the clinical presentation of portal hypertensive gastropathy (PHG). In addition, the inflammatory process is considered an aggravating factor for severity by contributing to gastric tissue injury. The aim of this study was to investigate the synergistic anti-inflammatory and antioxidant action of N-acetylcysteine (NAC) in the stomach of rats with PH. Materials and Methods:Eighteen Wistar male rats were used in this experimental protocol and were divided into three groups with six in each group: sham-operated (SO), partial portal vein ligation (PPVL), and PPVL + NAC. Treatment with NAC at a dose of 10 mg/kg (i.p.) was initiated on day 8 after surgery and continued for 7 days. We evaluated the expression of iNOS, NQO-1, HSP-90, and SOD by Western blot, as well as nuclear factor-kappa B (NF-κB) and tumor necrosis factor (TNF)-α staining by immunohistochemistry, in the rat stomach. Results:The PPVL group exhibited increased expression of HSP-90, iNOS, SOD, and NQO-1 when compared with controls. NAC reduced the expression of all studied proteins. Similarly, NF-κB and TNF-α staining was increased in PPVL animals versus controls and reduced in PPVL + NAC versus PPVL animals, respectively. Conclusion:These results suggest the effectiveness of NAC as a dual anti-inflammatory and antioxidant in animals with experimental PHG induced by partial ligation of the portal vein.

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Section: Discussionsupporting

confidence: 91%

Synergistic Antioxidant and Anti-Inflammatory Action of N-Acetylcysteine In Portal Hypertensive Gastropathy in Rats

Marques¹

2022

Hepatology Forum

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“…(Piech et al, 2003). Moreover, endothelial hsp90 expression (Ai et al, 2003), NOS activity and NO production (Shah et al, 1999) are increased in mesenteric vascular beds of rats with portal hypertension. Hsp90 overexpression has also been observed in cerebral microvessels of spontaneously hypertensive rats (Zhou et al, 2005).…”

Section: Endothelial Nitric Oxide and Hypertensionmentioning

confidence: 99%

Endothelial nitric oxide (NO) and its pathophysiologic regulation

Chatterjee¹,

Catravas²

2008

Vascular Pharmacology

212

163

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Nitric oxide (NO) is a gaseous lipophilic free radical generated by three distinct isoforms of nitric oxide synthases (NOS), type 1 or neuronal (nNOS), type 2 or inducible (iNOS) and type 3 or endothelial NOS (eNOS). Expression of eNOS is altered in many types of cardiovascular disease, such as atherosclerosis, diabetes and hypertension. The ubiquitous chaperone heat shock protein 90 (hsp90) associates with NOS and is important for its proper folding and function. Current studies point toward a therapeutic potential by modulating hsp90-NOS association in various vascular diseases. Here we review the transcriptional regulation of endothelial NOS and factors affecting eNOS activity and function, as well as the important vascular pathologies associated with altered NOS function, focusing on the regulatory role of hsp90 and other factors in NO-associated pathogenesis of these diseases. Keywords nitric oxide; hsp90; cardiovascular disease Transcriptional and post-transcriptional regulation of eNOS in endothelial cellsEndothelial cells have a constitutive expression of eNOS and like other constitutively expressed proteins, the eNOS promoter lacks the typical TATA box. Instead, it has other multiple cisregulatory DNA sequences like SP-1, GATA, activator protein-1, activator protein-2, nuclear factor-1, sheer stress response elements and sterol-regulatory elements (Marsden et al., 1993). The presence of these consensus sites is consistent with evidence showing that levels of eNOS transcripts are elevated by sheer stress (Davis et al., 2001;Woodman et al., 2005), exercise (Sessa et al., 1994;Yang et al., 2002) and hypoxia (Le Cras et al., 1996). Regulation of eNOS transcription by estrogens is still a matter of debate (Arnal et al., 1996;Kleinert et al., 1998), however, estradiol relaxes rat aortic segments via endothelium-dependent andindependent mechanisms involving the NO-cGMP signaling system (Abou-Mohamed et al., 2003). Both lipopolysaccharide (Arriero et al., 2000) and tumor necrosis factor-α (Yoshizumi et al., 1993) decrease eNOS gene expression by reducing the stability of eNOS mRNAs. Basal human eNOS transcription is controlled by two regulatory regions, the positive regulatory Address correspondence to: Dr. John D. Catravas Vascular Biology Center Medical College of Georgia Augusta, GA 30912-2500 USA e-mail: jcatrava@mcg.edu tel: +1-706-721-6338 fax: +1-706-721-9799. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errorsmaybe discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Searles, 2006). Moreover, these regions also contain differentially methylated nucleotides that restrict eNOS transcription largely in vascular endothel...

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“…Another mediator with eNOS-activating properties is heat shock protein 90 (Hsp90). Upregulation of Hsp90 and increased interaction of eNOS with Hsp90 contributes to the elevation in NOS activity in mesenteric vessels of PVL rats 66 67…”

Section: Mechanisms Of Vascular Hypocontractility and Vasodilation Inmentioning

confidence: 99%

Mechanisms of extrahepatic vasodilation in portal hypertension

Hennenberg

Trebicka

Sauerbruch

et al. 2008

Gut

148

161

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In liver cirrhosis, abnormal persistent extrahepatic vasodilation leads to hyperdynamic circulatory dysfunction which essentially contributes to portal hypertension. Since portal hypertension is a major factor in the development of complications in cirrhosis, the mechanisms underlying this vasodilation are of paramount interest. Extensive studies performed in cirrhotic patients and animals revealed that this vasodilation is associated on the one hand with enhanced formation of vasodilators, and on the other hand with vascular hyporesponsiveness to vasoconstrictors. The latter phenomenon has been termed "vascular hypocontractility". It is caused by a combination of different mechanisms and factors described in this review.

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Heat shock protein 90 is responsible for hyperdynamic circulation in portal hypertensive rats

Cited by 6 publications

References 32 publications

Synergistic Antioxidant and Anti-Inflammatory Action of N-Acetylcysteine In Portal Hypertensive Gastropathy in Rats

Synergistic Antioxidant and Anti-Inflammatory Action of N-Acetylcysteine In Portal Hypertensive Gastropathy in Rats

Endothelial nitric oxide (NO) and its pathophysiologic regulation

Mechanisms of extrahepatic vasodilation in portal hypertension

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