Decreased Vascular Endothelial Growth Factor Expression Is Associated With Cell Apoptosis in Low-Dose Aspirin-Induced Gastric Mucosal Injury

Cheng, Yiyun; Jia, Lin; Liu, Jinhong; Wang, Yali; Yan, Wei; Zhang, Mingkui

doi:10.1097/maj.0000000000000409

Cited by 10 publications

(3 citation statements)

References 32 publications

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“…The underlying mechanisms of NSAID-induced GI ulcers are not fully understood; however, they likely involve endoplasmic reticulum (ER)/mitochondrial stress and mucinous epithelia-microvascular barrier breakdown (Hawkey, 1996; Wolfe and Singh, 1999; Cheng et al, 2015). The effects of NSAIDs/aspirin on enterocytes and on vascular endothelial cells in the lamina propria are considered toxic/pathogenic based to the findings of i) the relatively high concentrations (mM) of conjugated NSAIDs through the enterohepatic circulation (Seitz and Boelsterli, 1998; Treinen-Moslen and Kanz, 2006), ii) direct toxic effects on intestinal mucosal epithelial and endothelial cells (break down the mucosal-vascular barrier), iii) effects on mitochondria (Somasundaram et al, 1997) and ER stress (Tsutsumi et al, 2004), and iv) mucosal injury related to active inflammation.…”

Section: Seh Inhibition Increases Eets Promotes Ulcer Healing and Imentioning

confidence: 99%

Epoxy-Oxylipins and Soluble Epoxide Hydrolase Metabolic Pathway as Targets for NSAID-Induced Gastroenteropathy and Inflammation-Associated Carcinogenesis

et al. 2019

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Polyunsaturated fatty acids (PUFAs) including epoxide-modified ω-3 and ω-6 fatty acids are made via oxidation to create highly polarized carbon-oxygen bonds crucial to their function as signaling molecules. A critical PUFA, arachidonic acid (ARA), is metabolized to a diverse set of lipids signaling molecules through cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 epoxygenase, or cytochrome P450 hydroxylase; however, the majority of ARA is metabolized into anti-inflammatory epoxides via cytochrome P450 enzymes. These short-lived epoxide lipids are rapidly metabolized or inactivated by the soluble epoxide hydrolase (sEH) into diol-containing products. sEH inhibition or knockout has been a practical approach to study the biology of the epoxide lipids, and has been shown to effectively treat inflammatory conditions in the preclinical models including gastrointestinal ulcers and colitis by shifting oxylipins to epoxide profiles, inhibiting inflammatory cell infiltration and activation, and enhancing epithelial cell defense via increased mucin production, thus providing further evidence for the role of sEH as a pro-inflammatory protein. Non-steroidal anti-inflammatory drugs (NSAIDs) with COX-inhibitor activity are among the most commonly used analgesics and have demonstrated applications in the management of cardiovascular disease and intriguingly cancer. Major side effects of NSAIDs however are gastrointestinal ulcers which frequently precludes their long-term application. In this review, we hope to bridge the gap between NSAID toxicity and sEH-mediated metabolic pathways to focus on the role of epoxy fatty acid metabolic pathway of PUFAs in NSAIDS-ulcer formation and healing as well as inflammation-related carcinogenesis. Specifically we address the potential application of sEH inhibition to enhance ulcer healing at the site of inflammation via their activity on altered lipid signaling, mitochondrial function, and diminished reactive oxygen species, and further discuss the significance of dual COX and sEH inhibitor in anti-inflammation and carcinogenesis.

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Section: Seh Inhibition Increases Eets Promotes Ulcer Healing and Imentioning

confidence: 99%

Epoxy-Oxylipins and Soluble Epoxide Hydrolase Metabolic Pathway as Targets for NSAID-Induced Gastroenteropathy and Inflammation-Associated Carcinogenesis

et al. 2019

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“…Developing extensive collateral circulation in ischemic myocardium is a promising therapy for treating IHD. Even though antiplatelet agent and statin are cornerstones for treating IHD, however, previous clinical studies showed that statin and aspirin was effective in decreasing VEGF levels and have no effects on promoting angiogenesis (Dworacka et al, 2014;Cheng et al, 2015). Recently, animal studies showed that VEFG for therapeutic angiogenesis could promotes collateral circulation in mouse heart by recruiting endothelial progenitor cells, and subsequently rescue myocardial tissue after an ischemic insult (Mallick et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Growth factor for therapeutic angiogenesis in ischemic heart disease: A meta-analysis of randomized controlled trials

Tan

Long

et al. 2022

Front. Cell Dev. Biol.

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Aim: This study was designed to systematically evaluate the effects of growth factor (GF) for therapeutic angiogenesis on ischemic heart disease (IHD) by pooling the results of randomized controlled trials (RCTs).Methods and Results: PubMed, EMBASE, and CENTRAL databases were searched from inception to October 2022. RCTs, investigating the effects of GF therapy on IHD, were included. The risk bias of included study was assessed according to Cochrane tool. Weighted mean difference (WMD), calculated with fixed effect model or random effect model, was used to evaluate the effects of GF therapy on left ventricular ejection fraction (LVEF) and Canadian Cardiovascular Society (CCS) angina class. Relative risk (RR) was used to evaluate the effects of GF therapy on all-cause mortality, major adverse cardiovascular events (MACE) and revascularization. Meta-analysis, meta-regression analysis and publication bias analysis were performed by RevMan 5.3 or Stata 15.1 software. Twenty-nine studies involving 2899 IHD patients (1,577 patients in GF group and 1,322 patients in control group) were included. Compared with the control group, GF therapy did not reduce all-cause mortality (RR: 0.82; 95% CI: 0.54–1.24; p = 0.341), MACE [(RR: 0.83; 95% CI: 0.61–1.12; p = 0.227), revascularization (RR: 1.27, 95% CI: 0.82–1.96, p = 0.290) and CCS angina class (WMD: −0.08, 95% CI: −0.36 to 0.20, p = 0.560). However, GF therapy could increase LVEF during short-term follow-up (<1 year).Conclusion: GF for therapeutic angiogenesis was beneficial for increasing LVEF during short-term follow-up (<1 year), however, the therapy was not efficacious in decreasing all-cause mortality, MACE and revascularization.

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“…Elevation of gastric mucosal injury and reduction of the expression level of vascular endothelial growth factor in gastric mucosa biopsy samples of 136 subjects at age 60 to 80 years taking 100 mg/d of aspirin have been observed in comparison with that of 48 age-matched healthy subjects[24]. The results suggest that the elderly are sensitive to aspirin-induced gastric injury.…”

Section: Effects Of Aspirin Use On the Elderlymentioning

confidence: 99%

Clinical use of low-dose aspirin for elders and sensitive subjects

Zhang

Fang

Chen

2019

WJCC

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The use of low-dose aspirin (LDA) has been a common preventive measure to reduce the risk of cardiovascular events. This is attributed to aspirin’s ability to inhibit platelet activation. On the other hand, the use of LDA in human subjects has been associated with the development of gastrointestinal injuries like ulcer and bleeding, especially for those sensitive subjects such as elder human subjects. This opinion review will summarize the recent clinical reports regarding the use of LDA and the development of gastrointestinal conditions in China. Based on these reports, it seems that the use of LDA is commonly associated with gastrointestinal injuries, and stopping its use leads to recovery in elderly subjects. Therefore, we would like to suggest that gastroduodenal health and conditions should be seriously taken into consideration when LDA is recommended to the elderly, or other alternative means to reduce the risk of cardiovascular events such as nutritional interventions should be suggested.

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Decreased Vascular Endothelial Growth Factor Expression Is Associated With Cell Apoptosis in Low-Dose Aspirin-Induced Gastric Mucosal Injury

Cited by 10 publications

References 32 publications

Epoxy-Oxylipins and Soluble Epoxide Hydrolase Metabolic Pathway as Targets for NSAID-Induced Gastroenteropathy and Inflammation-Associated Carcinogenesis

Epoxy-Oxylipins and Soluble Epoxide Hydrolase Metabolic Pathway as Targets for NSAID-Induced Gastroenteropathy and Inflammation-Associated Carcinogenesis

Growth factor for therapeutic angiogenesis in ischemic heart disease: A meta-analysis of randomized controlled trials

Clinical use of low-dose aspirin for elders and sensitive subjects

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