Role for Sterol Regulatory Element-Binding Protein in Activation of Endothelial Cells by Phospholipid Oxidation Products

Yeh, Michael W.; Cole, Amy L.; Choi, J.; Liu, Yi; Tulchinsky, Dmitry; Qiao, Jian-Hua; Fishbein, Michael C.; Dooley, Alek N.; Hovnanian, Talin; Mouilleseaux, Kevin; Vora, Devendra K.; Yang, Wen-Pin; Gargalovic, Peter S.; Kirchgessner, Todd G.; Shyy, John Y.‐J.; Berliner, Judith A.

doi:10.1161/01.res.0000146030.53089.18

Cited by 91 publications

(95 citation statements)

References 50 publications

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“…Consistent with in vitro studies indicating that oxPAPC induces cytokine production through a sterolregulatory element binding protein (SREBP)-mediated mechanism (39,40), renal SREBP-1c mRNA levels increased dramatically in mice fed the Western diet, compared with the same mice on a chow diet (22). The increased SREBP-1c mRNA levels were associated with a significant increase in renal triglyceride levels.…”

supporting

confidence: 78%

Anti-inflammatory apoA-I-mimetic peptides bind oxidized lipids with much higher affinity than human apoA-I

Lenten

Wagner

Jung

et al. 2008

Journal of Lipid Research

185

207

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4F is an anti-inflammatory, apolipoprotein A-I (apoA-I)-mimetic peptide that is active in vivo at nanomolar concentrations in the presence of a large molar excess of apoA-I. Physiologic concentrations (?35 mM) of human apoA-I did not inhibit the production of LDL-induced monocyte chemotactic activity by human aortic endothelial cell cultures, but adding nanomolar concentrations of 4F in the presence of ?35 mM apoA-I significantly reduced this inflammatory response. We analyzed lipid binding by surface plasmon resonance. The anti-inflammatory 4F peptide bound oxidized lipids with much higher affinity than did apoA-I.

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supporting

confidence: 78%

Anti-inflammatory apoA-I-mimetic peptides bind oxidized lipids with much higher affinity than human apoA-I

Lenten

Wagner

Jung

et al. 2008

Journal of Lipid Research

185

207

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“…This pathway directly regulates IL-8 transcription through binding to a novel gamma-interferon activation sequence (GAS) element in the IL-8 promoter. The sustained regulation of IL-8 transcription was found to be mediated by cholesterol depletion and the activation of the uncoupled eNOS/SREBP pathway 28,29 , which is sustained for up to 16 hours after Ox-PAPC treatment in HAEC. Increased binding of SREBP to an SRE element in the IL-8 promoter was also demonstrated.…”

Section: Chemokine Expressionmentioning

confidence: 96%

Endothelial cell regulation by phospholipid oxidation products

Berliner

Gharavi

2008

Free Radical Biology and Medicine

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Oxidized phospholipids accumulate in atherosclerotic lesions, on lipoproteins, in other states of chronic inflammation, on apoptotic cells, necrotic cells and cells exposed to oxidative stress. These lipids regulate the transcription of over 1000 gene, regulating many endothelial functions, by activating several different cell surface receptors and multiple signaling pathways. These lipids also have important effects not involving transcription that regulate cell junctions and leukocyte binding. Thus these lipids are potent regulators of endothelial cell function with broad effects comparable in extent but differing from those of cytokines.

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“…Oxidized phospholipids have been identified as potent mediators of inflammation (8,9). Berliner and colleagues have reported that oxidized phospholipids induce cytokine production in endothelial cells through induction of SREBP (10) via an endothelial nitric oxide synthase (eNOS)-mediated mechanism (11).…”

Section: /2mentioning

confidence: 99%

D-4F reduces EO6 immunoreactivity, SREBP-1c mRNA levels, and renal inflammation in LDL receptor-null mice fed a Western diet

Buga

Frank

Mottino

et al. 2008

Journal of Lipid Research

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LDL receptor-null (LDLR 2/2 ) mice on a Western diet (WD) develop endothelial dysfunction and atherosclerosis, which are improved by the apolipoprotein A-I (apoA-I) mimetic peptide D-4F. Focusing on the kidney, LDLR 2/2 mice were fed a WD with D-4F or the inactive control peptide scrambled D-4F (ScD-4F) added to their drinking water. The control mice (ScD-4F) developed glomerular changes, increased immunostaining for MCP-1/CCL2 chemokine, increased macrophage CD68 and F4/80 antigens, and increased oxidized phospholipids recognized by the EO6 monoclonal antibody in both glomerular and tublointerstitial areas. All of these parameters were significantly reduced by D-4F treatment, approaching levels found in wildtype C57BL/6J or LDLR 2/2 mice fed a chow diet. Sterolregulatory element binding protein-1c (SREBP-1c) mRNA levels and triglyceride levels were elevated in the kidneys of the control mice (ScD-4F) fed the WD compared with C57BL/6J and LDLR 2/2 mice on chow (P , 0.001 and P , 0.001, respectively) and compared with D-4F-treated mice on the WD (P , 0.01). There was no significant difference in plasma lipids, lipoproteins, glucose, blood pressure, or renal apoB levels between D-4F-and ScD-4F-treated mice. We conclude that D-4F reduced renal oxidized phospholipids, resulting in lower expression of SREBP-1c, which, in turn, resulted in lower triglyceride content and reduced renal inflammation. ) mice has been shown to induce atherosclerosis, endothelial dysfunction, and inflammation of brain arterioles associated with cognitive dysfunction, all of which have been reported to be significantly ameliorated by treatment with the oral apolipoprotein A-I (apoA-I) mimetic peptide D-4F without a change in plasma lipid levels or blood pressure (1-3).In addition to hyperlipidemia, feeding a WD to LDLR 2/2 mice results in insulin resistance and elevated plasma glucose levels (4, 5). A major problem facing Western societies is an increase in chronic renal disease that appears to be associated with dyslipidemia and diabetes in addition to hypertension (6). Dyslipidemia has been emphasized as a factor that can exacerbate hypertension-induced renal damage as well as a factor that by itself may have adverse effects on the kidney (6). Diet-induced obesity in C57BL/6J mice has been reported to cause lipid accumulation in kidneys and glomerulosclerosis via a sterol-regulatory element binding protein 1c (SREBP-1c)-dependent pathway (7). Oxidized phospholipids have been identified as potent mediators of inflammation (8,9). Berliner and colleagues have reported that oxidized phospholipids induce cytokine production in endothelial cells through induction of SREBP (10) via an endothelial nitric oxide synthase (eNOS)-mediated mechanism (11).Pritchard and colleagues reported that the apoA-I mimetic peptide L-4F (identical to D-4F except that the peptide is synthesized from L-amino acids) restored the balance between nitric oxide and superoxide anion production by eNOS in LDL-treated endothelial cells in culture (12). Injection of ...

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Role for Sterol Regulatory Element-Binding Protein in Activation of Endothelial Cells by Phospholipid Oxidation Products

Cited by 91 publications

References 50 publications

Anti-inflammatory apoA-I-mimetic peptides bind oxidized lipids with much higher affinity than human apoA-I

Anti-inflammatory apoA-I-mimetic peptides bind oxidized lipids with much higher affinity than human apoA-I

Endothelial cell regulation by phospholipid oxidation products

D-4F reduces EO6 immunoreactivity, SREBP-1c mRNA levels, and renal inflammation in LDL receptor-null mice fed a Western diet

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