Atorvastatin affects TLR4 clustering via lipid raft modulation

Chansrichavala, Praveen; Chantharaksri, Udom; Sritara, Piyamitr; Ngaosuwankul, Nathamon; Chaiyaroj, Sansanee C.

doi:10.1016/j.intimp.2010.04.027

Cited by 35 publications

(25 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(ii) Lipid rafts/caveolae are cell‐surface platforms in vascular cells for Toll‐like receptor 4 (TLR4) signaling and other signals which are involved in mediating vascular inflammation during atherogenesis [Villacorta et al, ; Sorci‐Thomas and Thomas, ]. Statins may exert their anti‐inflammatory pleiotropic effects by lowering levels of 7‐DHC, decreasing lipid rafts/caveolae, thus diminishing inflammatory signaling mediated by lipid rafts/caveolae in vascular cells [Chansrichavala et al, ]. (iii) Endothelial dysfunction is an early manifestation of ASCVD.…”

Section: Discussionmentioning

confidence: 99%

“…inflammation during atherogenesis [Villacorta et al, 2013;Sorci-Thomas and Thomas, 2016]. Statins may exert their antiinflammatory pleiotropic effects by lowering levels of 7-DHC, decreasing lipid rafts/caveolae, thus diminishing inflammatory signaling mediated by lipid rafts/caveolae in vascular cells [Chansrichavala et al, 2010]. (iii) Endothelial dysfunction is an early manifestation of ASCVD.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

7‐Dehydrocholesterol (7‐DHC), But Not Cholesterol, Causes Suppression of Canonical TGF‐β Signaling and Is Likely Involved in the Development of Atherosclerotic Cardiovascular Disease (ASCVD)

Huang

Liu

Chen

et al. 2016

J of Cellular Biochemistry

View full text Add to dashboard Cite

For several decades, cholesterol has been thought to cause ASCVD. Limiting dietary cholesterol intake has been recommended to reduce the risk of the disease. However, several recent epidemiological studies do not support a relationship between dietary cholesterol and/or blood cholesterol and ASCVD. Consequently, the role of cholesterol in atherogenesis is now uncertain. Much evidence indicates that TGF-β, an anti-inflammatory cytokine, protects against ASCVD and that suppression of canonical TGF-β signaling (Smad2-dependent) is involved in atherogenesis. We had hypothesized that cholesterol causes ASCVD by suppressing canonical TGF-β signaling in vascular endothelium. To test this hypothesis, we determine the effects of cholesterol, 7-dehydrocholesterol (7-DHC; the biosynthetic precursor of cholesterol), and other sterols on canonical TGF-β signaling. We use Mv1Lu cells (a model cell system for studying TGF-β activity) stably expressing the Smad2-dependent luciferase reporter gene. We demonstrate that 7-DHC (but not cholesterol or other sterols) effectively suppresses the TGF-β-stimulated luciferase activity. We also demonstrate that 7-DHC suppresses TGF-β-stimulated luciferase activity by promoting lipid raft/caveolae formation and subsequently recruiting cell-surface TGF-β receptors from non-lipid raft microdomains to lipid rafts/caveolae where TGF-β receptors become inactive in transducing canonical signaling and undergo rapid degradation upon TGF-β binding. We determine this by cell-surface 125I-TGF-β-cross-linking and sucrose density gradient ultracentrifugation. We further demonstrate that methyl-β-cyclodextrin (MβCD), a sterol-chelating agent, reverses 7-DHC-induced suppression of TGF-β-stimulated luciferase activity by extrusion of 7-DHC from resident lipid rafts/caveolae. These results suggest that 7-DHC, but not cholesterol, promotes lipid raft/caveolae formation, leading to suppression of canonical TGF-β signaling and atherogenesis. J. Cell. Biochem. 118: 1387–1400, 2017. © 2016 Wiley Periodicals, Inc.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

7‐Dehydrocholesterol (7‐DHC), But Not Cholesterol, Causes Suppression of Canonical TGF‐β Signaling and Is Likely Involved in the Development of Atherosclerotic Cardiovascular Disease (ASCVD)

Huang

Liu

Chen

et al. 2016

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…Atorvastatin is known to affect LPS indirectly by causing impaired TLR4 recruitment into the lipid raft, thereby affecting anti-inflammatory responses. 164 In a small study, optimized BP control with antihypertensive agents decreases endotoxin levels. 165 The mechanism of this beneficial effect is unknown.…”

Section: Miscellaneousmentioning

confidence: 99%

The Gut Microbiome, Kidney Disease, and Targeted Interventions

Ramezani

Raj

2014

Journal of the American Society of Nephrology

587

498

View full text Add to dashboard Cite

The human gut harbors .100 trillion microbial cells, which influence the nutrition, metabolism, physiology, and immune function of the host. Here, we review the quantitative and qualitative changes in gut microbiota of patients with CKD that lead to disturbance of this symbiotic relationship, how this may contribute to the progression of CKD, and targeted interventions to re-establish symbiosis. Endotoxin derived from gut bacteria incites a powerful inflammatory response in the host organism. Furthermore, protein fermentation by gut microbiota generates myriad toxic metabolites, including p-cresol and indoxyl sulfate. Disruption of gut barrier function in CKD allows translocation of endotoxin and bacterial metabolites to the systemic circulation, which contributes to uremic toxicity, inflammation, progression of CKD, and associated cardiovascular disease. Several targeted interventions that aim to re-establish intestinal symbiosis, neutralize bacterial endotoxins, or adsorb gut-derived uremic toxins have been developed. Indeed, animal and human studies suggest that prebiotics and probiotics may have therapeutic roles in maintaining a metabolically-balanced gut microbiota and reducing progression of CKD and uremia-associated complications. We propose that further research should focus on using this highly efficient metabolic machinery to alleviate uremic symptoms.

show abstract

“…Atorvastatin reduced the expression of TLR4 protein and mRNA and inhibited NF-kB activation in atherosclerotic plaques (Fang et al, 2014). Investigating the effects of anti-inflammatory effects of atorvastatin in murine pro-B cell lines, previous studies showed atorvastatin did not exert its inhibitory effect via TLR4 receptor-ligand binding mechanism, but instead, it impaired TLR4 recruitment into the lipid raft (Chansrichavala et al, 2010). Furthermore, atorvastatin inhibited NF-kB activation by stabilizing IkBa and inactivating ERK phosphorylation and reducing LPSinduced TLR4 mRNA expression in human umbilical vein endothelial cells .…”

Section: A Toll-like Receptor Signaling Inhibitionmentioning

confidence: 99%