Protective effects of acarbose against vascular endothelial dysfunction through inhibiting Nox4/NLRP3 inflammasome pathway in diabetic rats

Li, Xiao-Xue; Ling, Sunkai; Hu, Mingyue; Ma, Yu; Li, Yuan; Huang, Peilin

doi:10.1016/j.freeradbiomed.2019.09.015

Cited by 41 publications

(36 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…•− , which contributes to blocking NLRP3 inflammasome activation 100 . Furthermore, the reduced expression of NLRP3 inflammasome is also involved in the amelioration of vascular hyperpermeability by acarbose, which is attributed to the enhanced expression of junction protein ZO-1 and VE cadherin 100 .…”

Section: Hypoglycemic Agentsmentioning

confidence: 99%

“…Acarbose, a well-known α-glucosidase inhibitor, is a postprandial acting antidiabetic drug. It has been reported that acarbose has protective effects against vascular endothelial dysfunction by inhibiting the production of NOX4 oxidase-dependent O 2 •− , which contributes to blocking NLRP3 inflammasome activation 100 . Furthermore, the reduced expression of NLRP3 inflammasome is also involved in the amelioration of vascular hyperpermeability by acarbose, which is attributed to the enhanced expression of junction protein ZO-1 and VE cadherin 100 .…”

Section: Clinical Drugs and Nlrp3 Inflammasome And Endothelial Dysfunmentioning

confidence: 99%

See 1 more Smart Citation

NLRP3 inflammasome in endothelial dysfunction

et al. 2020

View full text Add to dashboard Cite

Inflammasomes are a class of cytosolic protein complexes. They act as cytosolic innate immune signal receptors to sense pathogens and initiate inflammatory responses under physiological and pathological conditions. The NLR-family pyrin domain-containing protein 3 (NLRP3) inflammasome is the most characteristic multimeric protein complex. Its activation triggers the cleavage of pro-interleukin (IL)-1β and pro-IL-18, which are mediated by caspase-1, and secretes mature forms of these mediators from cells to promote the further inflammatory process and oxidative stress. Simultaneously, cells undergo pro-inflammatory programmed cell death, termed pyroptosis. The danger signals for activating NLRP3 inflammasome are very extensive, especially reactive oxygen species (ROS), which act as an intermediate trigger to activate NLRP3 inflammasome, exacerbating subsequent inflammatory cascades and cell damage. Vascular endothelium at the site of inflammation is actively involved in the regulation of inflammation progression with important implications for cardiovascular homeostasis as a dynamically adaptable interface. Endothelial dysfunction is a hallmark and predictor for cardiovascular ailments or adverse cardiovascular events, such as coronary artery disease, diabetes mellitus, hypertension, and hypercholesterolemia. The loss of proper endothelial function may lead to tissue swelling, chronic inflammation, and the formation of thrombi. As such, elimination of endothelial cell inflammation or activation is of clinical relevance. In this review, we provided a comprehensive perspective on the pivotal role of NLRP3 inflammasome activation in aggravating oxidative stress and endothelial dysfunction and the possible underlying mechanisms. Furthermore, we highlighted the contribution of noncoding RNAs to NLRP3 inflammasome activation-associated endothelial dysfunction, and outlined potential clinical drugs targeting NLRP3 inflammasome involved in endothelial dysfunction. Collectively, this summary provides recent developments and perspectives on how NLRP3 inflammasome interferes with endothelial dysfunction and the potential research value of NLRP3 inflammasome as a potential mediator of endothelial dysfunction.

show abstract

Section: Hypoglycemic Agentsmentioning

confidence: 99%

Section: Clinical Drugs and Nlrp3 Inflammasome And Endothelial Dysfunmentioning

confidence: 99%

NLRP3 inflammasome in endothelial dysfunction

et al. 2020

View full text Add to dashboard Cite

show abstract

“…It increases permeability of human dermal microvascular endothelial cells by changing their cell junctions or cytoskeleton organization (Clark et al, 2007). Endothelial cells form tight barriers through tight junctions in a process regulated by the protein ZO-1 (Tornavaca et al, 2015), and VE-cadherin is an adhesion protein specifically located at tight junctions (Li et al, 2019). F-actin is the main cytoskeletal protein involved in cellular contraction, which is important for maintaining normal morphology and function (Deng et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of p38 MAPK Mitigates Lung Ischemia Reperfusion Injury by Reducing Blood–Air Barrier Hyperpermeability

et al. 2020

View full text Add to dashboard Cite

Background: Lung ischemia reperfusion injury (LIRI) is a complex pathophysiological process activated by lung transplantation and acute lung injury. The p38 mitogen-activated protein kinase (MAPK) is involved in breakdown of the endothelial barrier during LIRI, but the mechanism is still unclear. Therefore, we investigated the function of p38 MAPK in LIRI in vivo and in vitro.Methods: Sprague–Dawley rats were subjected to ischemia reperfusion with or without pretreatment with a p38 MAPK inhibitor. Lung injury was assessed using hematoxylin and eosin staining, and pulmonary blood–air barrier permeability was evaluated using Evans blue staining. A rat pulmonary microvascular endothelial cell line was infected with lentiviral expressing short hairpin (sh)RNA targeting p38 MAPK and then cells were subjected to oxygen/glucose deprivation and reoxygenation (OGD/R). Markers of endothelial destruction were measured by western blot and immunofluorescence.Results:In vivo LIRI models showed structural changes indicative of lung injury and hyperpermeability of the blood–air barrier. Inhibiting p38 MAPK mitigated these effects. Oxygen/glucose deprivation and reoxygenation promoted hyperpermeability of the endothelial barrier in vitro, but knockdown of p38 MAPK attenuated cell injury; maintained endothelial barrier integrity; and partially reversed injury-induced downregulation of permeability protein AQP1, endothelial protective protein eNOS, and junction proteins ZO-1 and VE-cadherin while downregulating ICAM-1, a protein involved in destroying the endothelial barrier, and ET-1, a protein involved in endothelial dysfunction.Conclusion: Inhibition of p38 MAPK alleviates LIRI by decreasing blood–air hyperpermeability. Blocking p38 MAPK may be an effective treatment against acute lung injury.

show abstract

“…In addition, carotid atherosclerosis was positively associated with plasma levels of IL-1β in DM subjects [ 56 ]. Similarly, another study found that high glucose induced the assembly and activation of NLRP3 inflammasome in rat endothelial cells, an effect that could be reverted by blocking NADPH oxidases 4-dependent ROS generation [ 57 ]. In addition to hyperglycemia-induced ROS overproduction, oxidized LDLs (oxLDLs) [ 58 ] and high mobility group box Protein 1 [ 59 ], two well-known agonist ligands of the receptor of AGEs (RAGE) [ 60 , 61 ], have been involved in the activation of NLRP3 that accompanies the atherosclerotic process.…”

Section: Diabetic Cardiovascular Diseasementioning

confidence: 99%

The Inflammasome in Chronic Complications of Diabetes and Related Metabolic Disorders

Menini

Iacobini

Vitale

et al. 2020

Cells

View full text Add to dashboard Cite

Diabetes mellitus (DM) ranks seventh as a cause of death worldwide. Chronic complications, including cardiovascular, renal, and eye disease, as well as DM-associated non-alcoholic fatty liver disease (NAFLD) account for most of the morbidity and premature mortality in DM. Despite continuous improvements in the management of late complications of DM, significant gaps remain. Therefore, searching for additional strategies to prevent these serious DM-related conditions is of the utmost importance. DM is characterized by a state of low-grade chronic inflammation, which is critical in the progression of complications. Recent clinical trials indicate that targeting the prototypic pro-inflammatory cytokine interleukin-1β (IL-1 β) improves the outcomes of cardiovascular disease, which is the first cause of death in DM patients. Together with IL-18, IL-1β is processed and secreted by the inflammasomes, a class of multiprotein complexes that coordinate inflammatory responses. Several DM-related metabolic factors, including reactive oxygen species, glyco/lipoxidation end products, and cholesterol crystals, have been involved in the pathogenesis of diabetic kidney disease, and diabetic retinopathy, and in the promoting effect of DM on the onset and progression of atherosclerosis and NAFLD. These metabolic factors are also well-established danger signals capable of regulating inflammasome activity. In addition to presenting the current state of knowledge, this review discusses how the mechanistic understanding of inflammasome regulation by metabolic danger signals may hopefully lead to novel therapeutic strategies targeting inflammation for a more effective treatment of diabetic complications.

show abstract

Protective effects of acarbose against vascular endothelial dysfunction through inhibiting Nox4/NLRP3 inflammasome pathway in diabetic rats

Cited by 41 publications

References 48 publications

NLRP3 inflammasome in endothelial dysfunction

NLRP3 inflammasome in endothelial dysfunction

Inhibition of p38 MAPK Mitigates Lung Ischemia Reperfusion Injury by Reducing Blood–Air Barrier Hyperpermeability

The Inflammasome in Chronic Complications of Diabetes and Related Metabolic Disorders

Contact Info

Product

Resources

About