Transcriptome Analysis Revealed Inflammation Is Involved in the Impairment of Human Umbilical Vein Endothelial Cells Induced by Post-hemorrhagic Shock Mesenteric Lymph

Wang, Qi; Chi, Zhenfen; Wei, Di; Zhao, Zhen-Ao; Zhang, Hong; Zhang, Limin; Liu, Yan-Xu; Kang, An-Ling; Zhao, Meng; Wang, Peng; Nie, Linghu; Niu, Chun‐Yu; Zhao, Zi‐Gang

doi:10.3389/fimmu.2020.01717

Cited by 7 publications

(6 citation statements)

References 54 publications

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“…After SGB treatment or not, rats were anesthetized with pentobarbital sodium for the establishment of a hemorrhagic shock model and the collection of mesenteric lymph according to our previous study (Zhao et al, 2012 ; Wang et al, 2020 ). In brief, rats received an acute hemorrhage (40 ± 2 mmHg of mean artery pressure for 60 min) and resuscitation with shed whole blood and Ringer's solution at a 1:1 ratio.…”

Section: Methodsmentioning

confidence: 99%

Autophagy Is Involved in Stellate Ganglion Block Reversing Posthemorrhagic Shock Mesenteric Lymph-Mediated Vascular Hyporeactivity

Wang

Zhao

et al. 2021

Front. Physiol.

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Objective: The aim of this study was to clarify the role of autophagy in stellate ganglion block (SGB) reversing posthemorrhagic shock mesenteric lymph (PHSML)-mediated vascular hyporeactivity.Methods: Hemorrhagic shock model in conscious rats was employed to observe the effects of SGB (0.2 ml of 0.25% ropivacaine hydrochloride hydrate) and autophagy inhibitor 3-methyladenine (3-MA; 30 mg/kg) on the vascular reactivity of second-order rat mesenteric arteries in vitro, while the effects of PHSML (1 ml/kg) and autophagy agonist rapamycin (Rapa, 10 mg/kg) on the beneficial effect of SGB were investigated. The cellular viability, contractility, and autophagy-related protein expressions in vascular smooth muscle cells (VSMCs) were detected following treatments of PHSML, PHSML obtained from the rats that underwent hemorrhagic shock plus SGB (PHSML-SGB), and PHSML plus 3-MA (5 mM), respectively.Results: Hemorrhagic shock significantly decreased the vascular reactivity to gradient norepinephrine (NE), which is reversed by the SGB treatment and 3-MA administration. On the contrary, PHSML intravenous infusion and Rapa administration inhibited the vascular contractile responses in rats that underwent hemorrhagic shock plus SGB treatment. PHSML treatment significantly inhibited the cellular viability and contractility in VSMCs, increased the expressions of LC3-II and Beclin 1, and decreased the expression of p62, along with opposite appearances in these indices following PHSML-SGB treatment. In addition, 3-MA counteracted the adverse roles of PHSML in these indices in VSMCs.Conclusion: SGB inhibits PHSML-mediated vascular hyporeactivity by reducing the excessive autophagy in VSMCs.

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Section: Methodsmentioning

confidence: 99%

Autophagy Is Involved in Stellate Ganglion Block Reversing Posthemorrhagic Shock Mesenteric Lymph-Mediated Vascular Hyporeactivity

Wang

Zhao

et al. 2021

Front. Physiol.

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“…Under inhalation anesthesia with 2% isoflurane (Shenzhen Ruiwald Life Technology Co., Ltd., Shenzhen, China) by the inhalation anesthesia machine for small animals (MATRX VMR; Midmark Corporation, Dayton, OH), before the surgical and hemorrhage procedures, either the authentic or sham SGB procedures were performed according to previous reports, with minor alterations (12,(15)(16)(17). After hemorrhagic shock (40 mm Hg for 90 min, followed by resuscitation with shed whole blood and equal Ringer's solution), the PHSML and PHSML-SGB were harvested from rats under anesthetic conditions (18)(19)(20).…”

Section: Experimental Design and Protocolsmentioning

confidence: 99%

STELLATE GANGLION BLOCK REVERSES PHSML-INDUCED VASCULAR HYPOREACTIVITY THROUGH INHIBITING AUTOPHAGY-MEDIATED PHENOTYPIC TRANSFORMATION OF VSMCs

Li,

Du,

Zhao

et al. 2023

Shock

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Post-hemorrhagic shock mesenteric lymph (PHSML) return-contributed excessive autophagy of vascular smooth muscle cells (VSMCs) is involved in vascular hypo-reactivity, which is inhibited by stellate ganglion block (SGB) treatment. The contractile phenotype of VSMCs transforms into a synthetic phenotype after stimulation with excessive autophagy. Therefore, we hypothesized that SGB ameliorates PHSML-induced vascular hypo-reactivity by inhibiting autophagy-mediated phenotypic transformation of VSMCs. To substantiate this hypothesis, a hemorrhagic shock model in conscious rats was employed to observe the effects of SGB intervention or intravenous infusion of the autophagy inhibitor 3-MA on intestinal blood flow and the expression of autophagy- and phenotype-defining proteins in mesenteric secondary artery tissues. We also investigated the effects of intraperitoneal administration of PHSML intravenous infusion and the autophagy agonist rapamycin (RAPA) on the beneficial effect of SGB. The results showed that hemorrhagic shock decreased intestinal blood flow and enhanced the expression of LC3 II/I, Beclin1, and matrix metalloproteinase 2, which were reversed by SGB or 3-MA treatment. In contrast, RAPA and PHSML administration abolished the beneficial effects of SGB. Furthermore, the effects of PHSML or PHSML obtained from rats treated with SGB (PHSML-SGB) on cellular contractility, autophagy, and VSMC phenotype were explored. Meanwhile, the effects of 3-MA on PHSML and RAPA on PHSML-SGB were observed. The results showed that PHSML, but not PHSML-SGB, incubation decreased VSMCs contractility and induced autophagy activation and phenotype transformation. Importantly, 3-MA administration reversed the adverse effects of PHSML, and RAPA treatment attenuated the effects of PHSML-SGB incubation on VSMCs. Taken together, the protective effect of SGB on vascular reactivity is achieved by inhibiting excessive autophagy-mediated phenotypic transformation of VSMCs to maintain their contractile phenotype.

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“…However, the mechanisms of disorder of cellular immune function induced by hemorrhagic shock are not fully understood. It is widely believed that PHSML reflux due to impaired mesenteric barrier and dysfunctional mesenteric lymph node in the body after hemorrhagic shock is strongly associated with distal tissue damage and decrease host resistance to microbial infection (11,(32)(33)(34). It has been reported that after mesenteric lymph node structure and function are damaged, the Th1/Th2 subsets of CD4 + T cells are dysregulated, and the proliferation and of CD4 + T cells are interrupted, thus leading to immune imbalance in the body (35)(36)(37).…”

Section: Effect Of Tlr2/tlr4-mediated Tipe2 On the Levels Of Cytokine...mentioning

confidence: 99%

“…Recent studies have found that the return of the posthemorrhagic shock mesenteric lymph (PHSML) as toxic product into the circulation is a key mechanism for multi-organ failure and organic immune dysfunction (11)(12)(13). Studies have shown that the PHSML causes multiple organ damage by elevating large amounts of cytokines (14).…”

Section: Introductionmentioning

confidence: 99%

TLR2/TLR4-Enhanced TIPE2 Expression Is Involved in Post-Hemorrhagic Shock Mesenteric Lymph-Induced Activation of CD4+T Cells

Jiang

Zhao

et al. 2022

Front. Immunol.

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PurposePost hemorrhagic shock mesenteric lymph (PHSML) return contributes to CD4+ T cell dysfunction, which leads to immune dysfunction and uncontrolled inflammatory response. Tumor necrosis factor α induced protein 8 like-2 (TIPE2) is one of the essential proteins to maintain the immune homeostasis. This study investigated the role of TIPE2 in regulation of CD4+ T lymphocyte function in interaction of PHSML and TLR2/TLR4.MethodsThe splenic CD4+ T cells were isolated from various mice (WT, TLR2-/-, TLR4-/-) by immunomagnetic beads, and stimulated with PHSML, normal lymphatic fluid (NML), respectively. Application of TIPE2-carrying interfering fragments of lentivirus were transfected to WT, TLR4-/-, and TLR2-/- CD4+ T cells, respectively. After interference of TIPE2, they were stimulated with PHSML and NML for the examinations of TIPE2, TLR2, and TLR4 mRNA expressions, proliferation, activation molecules on surface, and cytokine secretion function.ResultsPHSML stimulation significantly upregulated TIPE2, TLR2, and TLR4 mRNA expressions, decreased proliferation, CD25 expression, and IFN-γ secretion, and increased the secretion ability of IL-4 in WT CD4+ T cells. TIPE2 silencing enhanced proliferative capacity, upregulated CD25 expression, and increased IFNγ secretion in CD4+ T cells. PHSML stimulated TLR2-/-CD4+ T or TLR4-/-CD4+ T cells of which TIPE2 were silenced. TLR2 or TLR4 knockout attenuated PHSML-induced CD4+ T cells dysfunction; PHSML stimulation of silent TIPE2-expressing TLR2-/-CD4+ T or TLR4-/-CD4+ T revealed that the coexistence of low TIPE2 expression with lack of TLR2 or TLR4 eliminated this beneficial effect.ConclusionTIPE2 improves the PHSML-mediated CD4+T cells dysfunction by regulating TLR2/TLR4 pathway, providing a new intervention target following hemorrhagic shock-induced immune dysfunction.

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Transcriptome Analysis Revealed Inflammation Is Involved in the Impairment of Human Umbilical Vein Endothelial Cells Induced by Post-hemorrhagic Shock Mesenteric Lymph

Cited by 7 publications

References 54 publications

Autophagy Is Involved in Stellate Ganglion Block Reversing Posthemorrhagic Shock Mesenteric Lymph-Mediated Vascular Hyporeactivity

Autophagy Is Involved in Stellate Ganglion Block Reversing Posthemorrhagic Shock Mesenteric Lymph-Mediated Vascular Hyporeactivity

STELLATE GANGLION BLOCK REVERSES PHSML-INDUCED VASCULAR HYPOREACTIVITY THROUGH INHIBITING AUTOPHAGY-MEDIATED PHENOTYPIC TRANSFORMATION OF VSMCs

TLR2/TLR4-Enhanced TIPE2 Expression Is Involved in Post-Hemorrhagic Shock Mesenteric Lymph-Induced Activation of CD4+T Cells

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