CD36 signaling in vascular redox stress

Yang, Moua; Silverstein, Roy L.

doi:10.1016/j.freeradbiomed.2019.02.021

Cited by 48 publications

(33 citation statements)

References 105 publications

(133 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD36 is a multifunctional scavenger receptor, amongst other entities for oxidized phospholipids [25]. It is expressed in many cell types including enterocytes, myocytes, macrophages, endothelial cells, and platelets, and is of particular importance in the context of the effects of dyslipidaemia on inflammation and cardiovascular health [26] (see Section 5).…”

Section: Ffa Metabolism In Healthy Tissuesmentioning

confidence: 99%

Changes in Plasma Free Fatty Acids Associated with Type-2 Diabetes

2019

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2DM) is associated with increased total plasma free fatty acid (FFA) concentrations and an elevated risk of cardiovascular disease. The exact mechanisms by which the plasma FFA profile of subjects with T2DM changes is unclear, but it is thought that dietary fats and changes to lipid metabolism are likely to contribute. Therefore, establishing the changes in concentrations of specific FFAs in an individual’s plasma is important. Each type of FFA has different effects on physiological processes, including the regulation of lipolysis and lipogenesis in adipose tissue, inflammation, endocrine signalling and the composition and properties of cellular membranes. Alterations in such processes due to altered plasma FFA concentrations/profiles can potentially result in the development of insulin resistance and coagulatory defects. Finally, fibrates and statins, lipid-regulating drugs prescribed to subjects with T2DM, are also thought to exert part of their beneficial effects by impacting on plasma FFA concentrations. Thus, it is also interesting to consider their effects on the concentration of FFAs in plasma. Collectively, we review how FFAs are altered in T2DM and explore the likely downstream physiological and pathological implications of such changes.

show abstract

Section: Ffa Metabolism In Healthy Tissuesmentioning

confidence: 99%

Changes in Plasma Free Fatty Acids Associated with Type-2 Diabetes

2019

View full text Add to dashboard Cite

show abstract

“…CD36 is a multifunctional receptor that binds a variety of ligands [ 16 ]. It is expressed in many cell types, including macrophages, adipocytes, endothelial cells, and epithelial cells, and plays an essential role in many different biological processes [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Role of ASM/Cer/TXNIP signaling module in the NLRP3 inflammasome activation

et al. 2021

View full text Add to dashboard Cite

Background This study aimed to explore the effects of ceramide (Cer) on NLRP3 inflammasome activation and their underlying mechanisms. Methods Lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced NLRP3 inflammasome activation in J774A.1 cells and THP-1 macrophages was used as an in vitro model of inflammation. Western blotting and real-time PCR (RT-PCR) were used to detect the protein and mRNA levels, respectively. IL-1β and IL-18 levels were measured by ELISA. ASM assay kit and immunofluorescence were used to detect ASM activity and Cer content. Results Imipramine, a well-known inhibitor of ASM, significantly inhibited LPS/ATP-induced activity of ASM and the consequent accumulation of Cer. Additionally, imipramine suppressed the LPS/ATP-induced expression of thioredoxin interacting protein (TXNIP), NLRP3, caspase-1, IL-1β, and IL-18 at the protein and mRNA level. Interestingly verapamil, a TXNIP inhibitor, suppressed LPS/ATP-induced activation of TXNIP/NLRP3 inflammasome but did not affect LPS/ATP-induced ASM activation and Cer formation. TXNIP siRNA and verapamil inhibited C2-Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome. In addition, the pretreatment of cells with sulfo-N-succinimidyl oleate (SSO), an irreversible inhibitor of the scavenger receptor CD36, blocked Cer-induced upregulation of nuclear factor-κB (NF-κB) activity, TXNIP expression, and NLRP3 inflammasome activation. Inhibition of NF-κB activation by SN50 prevented Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome but did not affect CD36 expression. Conclusion This study demonstrated that the ASM/Cer/TXNIP signaling pathway is involved in NLRP3 inflammasome activation. The results documented that the CD36-dependent NF-κB-TXNIP signaling pathway plays an essential role in the Cer-induced activation of NLRP3 inflammasomes in macrophages.

show abstract

“…Furthermore, DKO platelets under metabolic stress have increased mitochondrial dysfunction, resulting in increased calpain activation and phosphatidylserine exposure, 8 which might also contribute to increased procoagulant platelet formation in DKO platelets. An interesting player in all of these processes is the scavenging receptor CD36 and its downstream effector ERK5, which is a redox sensor 31 . Signaling through this pathway by various agents has been shown to potentiate GPVI‐mediated signaling and subsequent procoagulant platelet formation 31 .…”

Section: Discussionmentioning

confidence: 99%

“…An interesting player in all of these processes is the scavenging receptor CD36 and its downstream effector ERK5, which is a redox sensor. 31 Signaling through this pathway by various agents has been shown to potentiate GPVI-mediated signaling and subsequent procoagulant platelet formation. 31 We hypothesize the increase in procoagulant platelets drives the increase in injurious platelet-neutrophil interactions in the hyperglycemic stroke brain.…”

Section: Discussionmentioning

confidence: 99%

“…31 Signaling through this pathway by various agents has been shown to potentiate GPVI-mediated signaling and subsequent procoagulant platelet formation. 31 We hypothesize the increase in procoagulant platelets drives the increase in injurious platelet-neutrophil interactions in the hyperglycemic stroke brain. However, future research is warranted to investigate how procoagulant platelets formation is altered in the setting of diabetes and stroke and whether targeting procoagulant platelet formation confers protection from ischemic stroke brain injury under hyperglycemic conditions.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Hyperglycemia exacerbates ischemic stroke outcome independent of platelet glucose uptake

Denorme

Portier

Kosaka

et al. 2021

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Objective Hyperglycemia is a common comorbidity for ischemic stroke and is associated with worsened neurological outcomes. Platelets are central mediators of ischemic stroke and hyperglycemia mediates platelet hyperactivity. In this study, we investigated the contribution of platelet glucose metabolism to ischemic stroke. Methods Mice lacking both Glut1 and Glut3 specifically in platelets (DKO) and their littermate controls (WT) were subjected to 1‐hour transient middle cerebral artery occlusion under normoglycemic and streptozotocin‐induced hyperglycemic conditions after which stroke outcomes, platelet activation, and platelet‐neutrophil aggregate (PNA) formation were examined. Results Under normoglycemic conditions, DKO mice were protected from ischemic stroke with smaller brain infarct volumes and improved cerebral blood flow. In addition, DKO mice had reduced platelet activation, PNA, and cerebral neutrophil recruitment after stroke. Hyperglycemia significantly increased infarct size and cerebral Evans blue extravasation and worsened neurological outcomes and cerebral blood flow in both WT and DKO mice, abolishing the protective effect witnessed under normoglycemic conditions. Flow cytometric analysis after stroke demonstrated increased platelet activation and neutrophil trafficking to the brain, independent of platelet glucose metabolism. Finally, platelets from healthy DKO mice were unable to become procoagulant upon dual agonist stimulation. Conversely, hyperglycemia increased platelet mitochondrial reactive oxygen species production which potentiated procoagulant platelet formation in WT mice and restored procoagulant platelet formation in DKO mice. Conclusion Hyperglycemia aggravates ischemic stroke outcome independent of platelet glucose uptake. Furthermore, we demonstrated that hyperglycemia primes procoagulant platelet formation. This underlines the therapeutic potential for strategies targeting procoagulant platelet formation for the treatment of acute ischemic stroke.

show abstract

CD36 signaling in vascular redox stress

Cited by 48 publications

References 105 publications

Changes in Plasma Free Fatty Acids Associated with Type-2 Diabetes

Changes in Plasma Free Fatty Acids Associated with Type-2 Diabetes

Role of ASM/Cer/TXNIP signaling module in the NLRP3 inflammasome activation

Hyperglycemia exacerbates ischemic stroke outcome independent of platelet glucose uptake

Contact Info

Product

Resources

About