Sustained retention of tetradecylthioacetic acid after local delivery reduces angioplasty-induced coronary stenosis in the minipig

Pettersen, Reidar J.; Muna, Ziad A.; Kuiper, Karel Kier-Jan; Svendsen, Einar; Müller, Fredrik; Aukrust, Pål; Berge, Rolf K.; Nordrehaug, Jan Erik

doi:10.1016/s0008-6363(01)00404-7

Cited by 11 publications

(7 citation statements)

References 42 publications

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“…Indeed, we found a significant 98% increased transcription of IL10 . Hence, indicating that TTA increases expression of IL10 in poly(I:C) activated macrophages, similar to the effects reported from human PBMCs stimulated with TTA [49,50]. …”

Section: Discussionsupporting

confidence: 84%

Anti-inflammatory effects of tetradecylthioacetic acid (TTA) in macrophage-like cells from Atlantic salmon (Salmo salar L.)

Grammes

Takle

2011

BMC Immunol

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BackgroundCommercial Atlantic salmon is fed diets with high fat levels to promote fast and cost-effective growth. To avoid negative impact of obesity, food additives that stimulate fat metabolism and immune function are of high interest. TTA, tetradecylthioacetic acid, is a synthetic fatty acid that stimulates mitochondrial β-oxidation most likely by activation of peroxysome proliferator-activated receptors (PPARs). PPARs are important transcription factors regulating multiple functions including fat metabolism and immune responses. Atlantic salmon experiments have shown that TTA supplemented diets significantly reduce mortality during natural outbreaks of viral diseases, suggesting a modulatory role of the immune system.ResultsTo gain new insights into TTA effects on the Atlantic salmon immune system, a factorial, high-throughput microarray experiment was conducted using a 44K oligo nucleotide salmon microarray SIQ2.0 and the Atlantic salmon macrophage-like cell line ASK. The experiment was used to determine the transcriptional effects of TTA, the effects of TTA in poly(I:C) elicited cells and the effects of pretreating the cells with TTA. The expression patterns revealed that a large proportion of genes regulated by TTA were related to lipid metabolism and increased mitochondrial β-oxidation. In addition we found that for a subset of genes TTA antagonized the transcriptional effects of poly(I:C). This, together with the results from qRT-PCR showing an increased transcription of anti-inflammatory IL10 by TTA, indicates anti-inflammatory effects.ConclusionsWe demonstrate that TTA has significant effects on macrophage-like salmon cells that are challenged by the artificial dsRNA poly(I:C). The immune stimulatory effect of TTA in macrophages involves increased lipid metabolism and suppressed inflammatory status. Thus, suggesting that TTA directs the macrophage-like cells towards alternative, anti-inflammatory, activation. This has positive implications for TTA as a feed additive.

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Section: Discussionsupporting

confidence: 84%

Anti-inflammatory effects of tetradecylthioacetic acid (TTA) in macrophage-like cells from Atlantic salmon (Salmo salar L.)

Grammes

Takle

2011

BMC Immunol

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Section: Discussionmentioning

confidence: 95%

“…37 We have previously shown that TTA reduces restenosis in pigs. 37 Selenium is a stronger reducing agent than sulfur, and our data indicate that TSA may reduce the degree of coronary artery intimal thickening in pigs undergoing PCI. These findings suggest that the antioxidant, antiinflammatory, and hypolipidemic properties of TSA may not merely be an in vitro phenomenon, but could induce antiproliferative effects after PCI in vivo.…”

Section: Discussionmentioning

confidence: 95%

Tetradecylselenoacetic Acid, a PPAR Ligand With Antioxidant, Antiinflammatory, and Hypolipidemic Properties

Dyrøy

Røst

Pettersen

et al. 2007

ATVB

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Objective-Antioxidants protect against oxidative stress and inflammation, which, in combination with hyperlipidemia, are important mediators of atherogenesis. Here we present a selenium-substituted fatty acid, tetradecylselenoacetic acid (TSA), which is hypothesized to have antioxidant, antiinflammatory, and hypolipidemic properties. Methods and Results-We show that TSA exerts antioxidant properties by delaying the onset of oxidation of human low density lipoprotein (LDL), by reducing the uptake of oxidized LDL in murine macrophages, and by increasing the mRNA level of superoxide dismutase in rat liver. TSA also showed antiinflammatory effects by suppressing the release of interleukin (IL)-2 and -4, and by increasing the release of IL-10 in human blood leukocytes. In addition, TSA decreased the plasma triacylglycerol level and increased the mitochondrial fatty acid ␤-oxidation in rat liver. In pigs, TSA seemed to reduce coronary artery intimal thickening after percutaneous coronary intervention. In HepG2 cells TSA activated all peroxisome proliferator-activated receptors (PPARs) in a dose-dependent manner. Conclusions-Our data suggest that TSA exert potent antioxidant, antiinflammatory, and hypolipidemic properties, potentially involving PPAR-related mechanisms. Based on these effects, it is tempting to hypothesize that TSA could be an interesting antiatherogenic approach to atherosclerotic disorders. A therosclerosis is regarded as an inflammatory disorder of the vascular wall, where multiple factors contribute to a persistent and self-perpetual inflammation within the atherosclerotic lesions. [1][2][3][4][5] There is also a consensus that atherosclerosis represents a state of elevated oxidative stress characterized by lipid and protein oxidation in the vascular wall. 6 Enhanced inflammation and oxidative stress seem to represent a vicious circle in atherogenesis, and therapeutic options directed against these processes seems like a reasonable approach in the management of atherosclerotic disorders.We have previously shown that tetradecylthioacetic acid (TTA), a modified fatty acid with a sulfur atom in the third position of the carbon backbone, promotes mitochondrial and peroxisomal proliferation, and decreases serum lipid levels in animal models. 7-9 TTA also shows antioxidant effects in vitro 10 and encompasses antiinflammatory properties in human leukocytes. 11 The pleiotropic effects of TTA seem to involve activation of peroxisome proliferator-activated receptors (PPARs), 12,13 which are receptors that serves as an important link between lipid metabolism and inflammation. 14 -17 Tetradecylselenoacetic acid (TSA) is a novel fatty acid which in comparison to TTA has a selenium atom instead of a sulfur atom in third position of the carbon backbone. As with TTA, 18 this modification makes TSA resistant to fatty acid ␤-oxidation. A previous in vitro study has demonstrated that TSA is a stronger antioxidant than TTA. 19 Based on these findings and its relation to TTA, we hypothesized that TSA also exerts poten...

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“…TTA inhibits proliferation of smooth muscle cells and has the ability to attenuate TNFα-mediated endothelial cell activity involving both PPARα-dependent and –independent pathways [16]. As previously reported, TTA was taken up in the arterial wall [18]. Thus, its anti-atherosclerotic effect could be a direct action on the vascular cells with anti-inflammatory and antioxidative effects, at least partly related to its effect of the local fatty acid composition.…”

Section: Discussionmentioning

confidence: 97%

“…The anti-inflammatory effects of TTA appear to involve both PPARα-dependent and –independent pathways [16]. Finally, TTA is found to be present in the coronary wall [18], suggesting a potential for a direct effect on coronary atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

An Immunomodulating Fatty Acid Analogue Targeting Mitochondria Exerts Anti-Atherosclerotic Effect beyond Plasma Cholesterol-Lowering Activity in apoE-/- Mice

et al. 2013

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Tetradecylthioacetic acid (TTA) is a hypolipidemic antioxidant with immunomodulating properties involving activation of peroxisome proliferator-activated receptors (PPARs) and proliferation of mitochondria. This study aimed to penetrate the effect of TTA on the development of atherosclerotic lesions in apolipoprotein (apo)-E-/- mice fed a high-fat diet containing 0.3% TTA for 12 weeks. These mice displayed a significantly less atherosclerotic development vs control. Plasma cholesterol was increased by TTA administration and triacylglycerol (TAG) levels in plasma and liver were decreased by TTA supplementation, the latter, probably due to increased mitochondrial fatty acid oxidation and reduced lipogenesis. TTA administration also changed the fatty acid composition in the heart, and the amount of arachidonic acid (ARA) and eicosapentaenoic acid (EPA) was reduced and increased, respectively. The heart mRNA expression of inducible nitric oxidase (NOS)-2 was decreased in TTA-treated mice, whereas the mRNA level of catalase was increased. Finally, reduced plasma levels of inflammatory mediators as IL-1α, IL-6, IL-17, TNF-α and IFN-γ were detected in TTA-treated mice. These data show that TTA reduces atherosclerosis in apoE-/- mice and modulates risk factors related to atherosclerotic disorders. TTA probably acts at both systemic and vascular levels in a manner independent of changes in plasma cholesterol, and triggers TAG catabolism through improved mitochondrial function.

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Sustained retention of tetradecylthioacetic acid after local delivery reduces angioplasty-induced coronary stenosis in the minipig

Cited by 11 publications

References 42 publications

Anti-inflammatory effects of tetradecylthioacetic acid (TTA) in macrophage-like cells from Atlantic salmon (Salmo salar L.)

Anti-inflammatory effects of tetradecylthioacetic acid (TTA) in macrophage-like cells from Atlantic salmon (Salmo salar L.)

Tetradecylselenoacetic Acid, a PPAR Ligand With Antioxidant, Antiinflammatory, and Hypolipidemic Properties

An Immunomodulating Fatty Acid Analogue Targeting Mitochondria Exerts Anti-Atherosclerotic Effect beyond Plasma Cholesterol-Lowering Activity in apoE-/- Mice

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