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At least 1,081 records · Page 60Linked to original sources
PubMed2002

Lymphocytic infundibulo- neurohypophysitis with hypothalamic and optic pathway involvement: report of a case and review of the literature.

BACKGROUND: Lymphocytic adenohypohysitis and lymphocytic infundibulo-neurohypophysitis are rare auto-immune mediated diseases of the anterior and posterior pituitary, respectively. The former usually manifests as insufficiency of anterior pituitary hormone secretion, associated in many patients with disturbances of vision. The latter presents as diabetes insipidus of central origin. They present most commonly in pregnant or postpartum females. There have been infrequent reports in females with no association with pregnancy, and in males. CASE DESCRIPTION: We present a nulliparous female with central diabetes insipidus, pan-hypopituitarism, and severely impaired vision. Magnetic resonance imaging demonstrated a large mass involving the hypothalamus, infundibulum, optic nerves, chiasm, and tracts. At operation, the optic pathways were found to be grossly involved in the inflammatory mass. Histological examination of a biopsy demonstrated a nonspecific, mixed inflammatory infiltrate, composed predominantly of lymphocytes and plasma cells. She responded dramatically to treatment with dexamethasone, with disappearance of the mass on serial imaging studies and improvement in vision. In addition, she received hormone replacement therapy. CONCLUSION: We present a case of lymphocytic infundibulo-neurohypophysitis unique in the degree of optic pathway inflammatory involvement, with a documented response to steroids.

Adrenocorticotropic Hormone↗
PubMed2006

The inhibition of LPS-induced production of inflammatory cytokines by HSP70 involves inactivation of the NF-kappaB pathway but not the MAPK pathways.

The objective of this study was to evaluate the negative regulatory role of heat shock protein 70 (HSP70) on endotoxin-induced activation of inflammatory cytokine signaling pathways in a macrophage cell line. Our studies show that elevation of HSP70 either by activation of the heat shock response (HSR) or through forced expression of the hsp70.1 gene downregulates cytokine expression. Our experiments showed that activation of the HSR and HSP70 overexpression could inhibit LPS-mediated expression of the proinflammatory cytokines TNF-alpha and IL-1 at the mRNA and protein levels. We also investigated the effects of HSP70 elevation on signaling pathways downstream of LPS and its receptors, including the NF-kappaB and mitogen-activated protein kinase (MAPK) pathways. The effects of HSP70 on cytokine expression were correlated with its effects on activation of NF-kappaB, a known activator of the tnfalpha and Il-1 genes. Overexpression of HSP70 inhibited the nuclear translocation of p65, the transcriptionally active component of the NF-kappaB complex, and prevented the degradation of IkappaBalpha, the regulator of NF-kappaB activity. However, HSP70 elevation did not markedly inhibit signaling through the MAPK arm of the LPS-induced pathway, suggesting that the effects of HSP70 are mediated primarily through the NF-kappaB cascade. Our experiments therefore suggested that elevated levels of HSP70 inhibit LPS-induced production of inflammatory cytokines by a mechanisms involving inactivation of NF-kappaB but cast doubt on significant role for the MAPK pathway in these effects.

Active Transport, Cell Nucleus↗
PubMed2003

Bacterial lipopolysaccharide directly induces angiogenesis through TRAF6-mediated activation of NF-kappaB and c-Jun N-terminal kinase.

The intracellular pathways by which inflammatory mediators transmit their angiogenic signals is not well studied. The effects of a potent inflammatory mediator, bacterial lipopolysaccharide (LPS), are transmitted through Toll-like receptors (TLRs). A major, although not exclusive, LPS/TLR intracellular signaling pathway is routed through TNF (tumor necrosis factor) receptor associated factor 6 (TRAF6). In this report we demonstrate that LPS directly stimulates endothelial sprouting in vitro. By blocking TRAF6 activity using retroviral expression of a dominant-negative TRAF6 in endothelial cells, we show that TRAF6 is absolutely required for the LPS-initiated angiogenic response in vitro and in vivo. Inhibition of either c-Jun N-terminal kinase (JNK) activity or nuclear factor kappaB (NF-kappaB) activity, downstream of TRAF6, is sufficient to inhibit LPS-induced endothelial sprouting. In contrast, only inhibition of NF-kappaB, but not JNK, activity blocks basic fibroblast growth factor (bFGF)-induced angiogenesis. Our findings thus demonstrate a direct endothelial-stimulatory role of LPS in initiating angiogenesis through activation of TRAF6-dependent signaling pathways.

Animals↗
PubMed2006

Phenolic-rich fraction from Rhus verniciflua Stokes (RVS) suppress inflammatory response via NF-kappaB and JNK pathway in lipopolysaccharide-induced RAW 264.7 macrophages.

The effects of phenolic-rich fraction (PRF) from Rhus verniciflua Stokes (Anacardiaceae) on the activities of cellular signaling molecules that mediate inflammatory responses in LPS-induced RAW 264.7 macrophages were investigated. At various concentrations of PRF significantly inhibited NO, PGE(2) and TNF-alpha production in LPS-induced RAW 264.7 macrophage cells. The PRF also significantly inhibited iNOS and COX-2 protein expression in LPS-induced RAW 264.7 macrophage in a concentration-dependent manner. Transcription factor NF-kappaB plays a key role for the inducible expression of genes mediating proinflammatory effects and here, we show that PRF can inhibit the induction of NF-kappaB activity. The PRF effectively inhibited the iNOS and COX-2 protein expression through suppression of phospho-JNK1/2 activation. Study using PDA HPLC has found that the PRF contains several low molecular compounds (i.e. p-coumaric acid, fustin, kaempferol-3-O-glucoside, sulfuretin, butein, kaempferol). Our results indicate that the anti-inflammatory properties of PRF might result from the inhibition of pro-inflammatory mediators (e.g., NO, PGE(2) and TNF-alpha) by suppression of such signaling pathways as NF-kappaB and JNK1/2.

Animals↗
PubMed2004

The impact of the inflammatory response on coagulation.

Inflammation contributions to the thrombotic response involve both cellular and humoral modulation. Inflammation impacts the initiation, propagation and the inhibitory phases of blood coagulation. Inflammatory mediators like endotoxin and tumor necrosis factor alpha (TNF alpha) elicit the expression of tissue factor on blood cells. Under normal circumstance, negatively charged membrane surfaces are limiting so that, even if some activated coagulation factors are generated, propagation of the coagulant stimulus is minimal. Complement activation, however, or exposure of collagen in combination with thrombin, provides a potent stimulus eliciting the exposure of negatively charged phospholipid membrane surfaces. Natural anticoagulant mechanisms limit the thrombotic response, but these pathways are depressed by inflammatory mediators. The protein C pathway is one of the major targets. Thrombomodulin and the endothelial cell protein C receptor are both required for optimal protein C activation, but both are down regulated by inflammatory mediators. Furthermore, free protein S levels often decrease resulting in impaired anticoagulant function of the activated protein C that is generated. In addition, anti-phospholipid antibodies severely impair the protein C pathway further inhibiting this pathway in inflammatory states associated with auto-immunity. In addition to shifting the hemostatic system in favor of clot formation, inflammation elevates the levels of plasminogen activator inhibitor thereby decreasing fibrinolytic activity. The procoagulant impact of inflammation can also be seen at the cellular level. Inflammatory mediators like interleukin 6 can increase both platelet count and their responsiveness to agonists like thrombin. All of these events tend to shift the hemostatic balance in favor of clot formation.

Animals↗
PubMed2005

Two-way interactions between inflammation and coagulation.

Activation of inflammatory and coagulation pathways is important in the pathogenesis of vascular disease. There is ample evidence that extensive cross-talk between these two systems exists, whereby inflammation not only leads to activation of coagulation, but coagulation also markedly affects inflammatory activity. The main interfaces linking coagulation and inflammation are the tissue factor pathway, thrombin, the protein C system and the fibrinolytic (or plasminogen-plasmin) system. Proinflammatory cytokines and chemokines can affect all these coagulation mechanisms, and vice versa, activated coagulation proteases and physiological anticoagulants or components of the plasminogen-plasmin system can modulate inflammation by specific cell receptors. The intricate relationship between inflammation and coagulation may not only be relevant for vascular thrombotic disease but also has major consequences in the pathogenesis of microvascular failure and subsequent multiple organ failure in the setting of severe infection. This review focuses on the present understanding of the bidirectional relationship between inflammation and coagulation.

Antigens↗
PubMed1984

Activation of a 15-lipoxygenase/leukotriene pathway in human polymorphonuclear leukocytes by the anti-inflammatory agent ibuprofen.

Human peripheral blood polymorphonuclear leukocytes (PMNs) metabolized [14C]arachidonic acid predominantly by lipoxygenase pathways. The major products were 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) and 15-HETE. These and other lipoxygenase products, including their derived leukotrienes, have been implicated as mediators of inflammatory and allergic reactions. In human platelets, the nonsteroidal anti-inflammatory drug ibuprofen inhibited production of the cyclooxygenase product thromboxane B2 (I50 = 65 microM), whereas the lipoxygenase product 12-HETE was not appreciably affected even at 5 mM ibuprofen. The 5-lipoxygenase of human PMNs (measured by 5-HETE formation) was inhibited by ibuprofen but was about six times less sensitive (I50 = 420 microM) than the platelet cyclooxygenase. The unexpected observation was made that the human PMN 15-lipoxygenase/leukotriene pathway was selectively activated by 1-5 mM ibuprofen. Metabolites were identified by ultraviolet spectroscopy, by radioimmunoassay, or by retention times on high pressure liquid chromatography in comparison with authentic standards. The major product was 15-HETE; and in all of 19 donors tested, 15-HETE formation was stimulated up to 20-fold by 5 mM ibuprofen. Other identified products included 12-HETE and 15- and 12-hydroperoxyeicosatetraenoic acid. Activation of the 15-lipoxygenase by ibuprofen occurred within 1 min and was readily reversible. The effects of aspirin, indomethacin, and ibuprofen on the PMN 15-lipoxygenase were compared in six donors. Ibuprofen produced an average 9-fold stimulation of the enzyme, whereas aspirin and indomethacin resulted in an average 1.5- and 2-fold enhancement, respectively.

Arachidonate Lipoxygenases↗
PubMed2007

The regulation of the inflammatory response through nuclear factor-kappab pathway by angiotensin IV extends the role of the renin angiotensin system in cardiovascular diseases.

The renin angiotensin system (RAS) participates in the pathogenesis of cardiovascular diseases. Although angiotensin II has been considered the effector peptide of RAS, accumulating evidence shows that other RAS peptides also posses important functions, some of them involved in cardiovascular pathology. Many studies support the importance of N-terminal angiotensin degradation product, angiotensin IV (AngIV), in the fields of cognition, renal metabolism, and pathophysiologic conditions. The novel data discussed here show that AngIV could contribute to cardiovascular damage. Angiotensin IV can be generated by degradation of angiotensin II, by aminopeptidase (AP) N, or by other proteases, which could be activated during tissue damage, suggesting that elevated AngIV levels can be found in pathologic conditions. Angiotensin IV binds to a specific receptor, AT(4), which has recently been identified as an insulin-regulated AP. In vascular cells, correspondence between AT(4) binding sites and insulin-regulated AP has been described. Angiotensin IV regulates cell growth in cardiac fibroblasts, endothelial cells, and vascular smooth muscle cells (VSMCs). In VSMC, AngIV, through AT(4), independently of AT(1) and AT(2) receptors, activates the nuclear factor-kappaB pathway and up-regulates several nuclear factor-kappaB-related genes, including the monocyte chemokine monocyte chemoattractant protein-1, the adhesion molecule intercellular adhesion molecule-1, and the cytokines interleukin 6 and tumor necrosis factor alpha. These data indicate that AngIV could be involved in the vascular inflammatory response. Thus, in endothelial cells and VSMC, AngIV up-regulates plasminogen activator inhibitor-1 expression and could participate in thrombus formation. These results reveal novel concepts of RAS in the cardiovascular system, suggesting that AngIV could play an active role in vascular diseases.

Angiotensin II↗
PubMed2002

Methamphetamine-induced TNF-alpha gene expression and activation of AP-1 in discrete regions of mouse brain: potential role of reactive oxygen intermediates and lipid peroxidation.

Cellular and molecular mechanisms of methamphetamine (METH)-induced neurotoxicity may involve alterations of cellular redox status and induction of inflammatory genes. To study this hypothesis, molecular signaling pathways of METH-induced inflammatory responses via activation of redox-sensitive transcription factors were investigated in discrete regions (corpus striatum, frontal cortex, and hippocampus) of mouse brain. Intraperitoneal injection of METH at a dose of 10 mg/kg body weight resulted in a significant increase in oxidative stress, as measured by 2,7-dichlorofluorescein (DCF) fluorescence assay, thiobarbituric acid-reactive substances (TBARS), and total glutathione levels. Glutathione peroxidase activity was also significantly increased after METH exposure. In addition, DNA binding activity of activator protein-1 (AP-1), a redox-responsive transcription factor, was increased in all studied brain regions in response to METH treatment. Because AP-1 is known to regulate expression of inflammatory genes, levels of TNF-alpha mRNA were also studied. Expression of the tumor necrosis factor-alpha (TNF-alpha) gene was induced 3 h after METH injection and remained elevated for up to 6 h of METH exposure. In addition, stimulation of the TNF-alpha gene was associated with increased TNF-a protein production in the frontal cortex. These results suggest that METH-induced disturbances in cellular redox status and that activation of AP-1 can play a critical role in signaling pathways leading to upregulation of inflammatory genes in vivo. Furthermore, these data provide evidence for the role of oxidative stress in the neurotoxic effects of METH.

Animals↗
PubMed2002

Activation of nuclear orphan receptor NURR1 transcription by NF-kappa B and cyclic adenosine 5'-monophosphate response element-binding protein in rheumatoid arthritis synovial tissue.

Modulation of the NURR subfamily of nuclear receptors may be an important mechanism regulating pathways associated with inflammatory joint disease. We examined the signaling mechanisms through which inflammatory mediators, produced by rheumatoid arthritis (RA) synovial tissue, contribute to the regulation of the NURR subfamily. Markedly enhanced expression of NURR1 is observed in synovial tissue of patients with RA compared with normal subjects. Modulation by proinflammatory mediators in primary RA and normal synoviocytes shows that PGE(2), IL-1beta, and TNF-alpha markedly enhance NURR1 mRNA and protein levels in contrast to other subfamily members, NUR77 and NOR-1. We have established that transcriptional activation of the NURR1 gene by IL-1beta and TNF-alpha requires a proximal promoter region that contains a consensus NF-kappaB DNA-binding motif. IL-1beta- and TNF-alpha-induced NF-kappaB binding to this site is due predominantly to p65-p50 heterodimer and p50 homodimer subunit protein complexes. We further demonstrate a direct CREB-1-dependent regulation by PGE(2) situated at promoter region -171/-163. Moreover, analyses confirm the presence of CREB-1 and NF-kappaB p50 and p65 subunit binding to the NURR1 promoter under basal conditions in freshly explanted RA synovial tissue. In summary, enhanced NF-kappaB- and CREB-1-binding activity on the NURR1 promoter by inflammatory mediators delineates novel mechanisms in the regulation of NURR1 transcription. PGE(2)-, TNF-alpha-, and IL-1beta-dependent stimulation of the NURR1 gene implies that NURR1 induction represents a point of convergence of at least two distinct signaling pathways, suggesting an important common role for this transcription factor in mediating multiple inflammatory signals.

Arthritis, Rheumatoid↗
PubMed2026

Corticosteroids in ARDS: old controversies, new insights, and future directions.

Corticosteroids modulate key inflammatory and fibroproliferative pathways involved in ARDS through genomic and non-genomic glucocorticoid receptor signaling. Advances in ARDS pathophysiology have highlighted the importance of timing, inflammatory burden, and host response in determining treatment efficacy. Clinical evidence supports corticosteroid use in moderate-to-severe ARDS, particularly in COVID-19 ARDS and severe community-acquired pneumonia, with reductions in mortality and duration of mechanical ventilation. However, treatment effects remain heterogeneous across etiologies and biological subphenotypes. Recent identification of hyperinflammatory and hypoinflammatory ARDS phenotypes suggests that corticosteroid responsiveness is not uniform. Hyperinflammatory phenotypes and septic ARDS appear more likely to benefit, whereas evidence remains limited or conflicting in influenza-associated and non-septic ARDS. Long-term effects and adverse outcomes, including metabolic complications and ICU-acquired weakness, remain insufficiently characterized. Future research is increasingly focused on precision medicine approaches integrating biomarkers, adaptive platform trials, and phenotype-guided strategies. Emerging developments include lung-targeted corticosteroid delivery systems and selective glucocorticoid receptor modulators designed to improve efficacy while reducing systemic toxicity. Corticosteroids should therefore be considered a context-dependent therapy whose benefit is influenced by etiology, disease stage, inflammatory phenotype, and timing of administration.

Humans↗
PubMed2002

Opposite effects of galectin-1 on alternative metabolic pathways of L-arginine in resident, inflammatory, and activated macrophages.

Recent evidence has implicated galectins and their carbohydrate ligands as master regulators of the inflammatory response. Galectin-1, a member of this family, has shown specific anti-inflammatory and immunoregulatory effects. To gain insight into the potential mechanisms involved in these effects, we investigated the effects of galectin-1 in L-arginine metabolism of peritoneal rat macrophages. Pretreatment of macrophages with galectin-1 resulted in a dose- and time-dependent inhibition of lipopolysaccharide-induced nitric oxide (NO) production, accompanied by a decrease in inducible nitric oxide synthase (iNOS) expression (the classic pathway of L-arginine). On the other hand, galectin-1 favored the balance toward activation of L-arginase, the alternative metabolic pathway of L-arginine. Inhibition of NO production was not the result of increased macrophage apoptosis because addition of this beta-galactoside-binding protein to macrophages under the same experimental conditions did not affect the apoptotic threshold of these cells. To understand how endogenous galectin-1 is regulated in macrophages under inflammatory stress, we finally explored the ultrastructural distribution, expression, and secretion of galectin-1 in resident, inflammatory, and activated macrophages. This study provides an alternative cellular mechanism based on the modulation of L-arginine metabolism to understand the molecular basis of the anti-inflammatory properties displayed by this carbohydrate-binding protein.

Animals↗
PubMed2006

Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages.

OBJECTIVE: Previous studies demonstrated that obese adipose tissue is characterized by increased infiltration of macrophages, suggesting that they might represent an important source of inflammation. Using an in vitro coculture system composed of 3T3-L1 adipocytes and RAW264 macrophages, we previously demonstrated that saturated fatty acids (FAs) and tumor necrosis factor (TNF)-alpha derived from adipocytes and macrophages, respectively, play a major role in the coculture-induced inflammatory changes. METHODS AND RESULTS: Coculture of adipocytes and macrophages resulted in the activation of nuclear factor-kappaB (NF-kappaB), a primary regulator of inflammatory responses, in both cell types. Pharmacological inhibition of NF-kappaB markedly suppressed the coculture-induced production of proinflammatory cytokines and adipocyte lipolysis. Peritoneal macrophages obtained from Toll-like receptor 4 (TLR4) mutant mice exhibited marked attenuation of TNFalpha production in response to saturated FAs. Notably, coculture of hypertrophied adipocytes and TLR4-mutant macrophages resulted in marked inhibition of proinflammatory cytokine production and adipocyte lipolysis. We also observed that endogenous FAs, which are released from adipocytes via the beta3-adrenergic stimulation, resulted in the activation of the TLR4/NF-kappaB pathway. CONCLUSIONS: These findings suggest that saturated FAs, which are released in large quantities from hypertrophied adipocytes via the macrophage-induced adipocyte lipolysis, serve as a naturally occurring ligand for TLR4, thereby inducing the inflammatory changes in both adipocytes and macrophages through NF-kappaB activation.

Adipocytes↗
PubMed2006

PPARs and other nuclear receptors in inflammation.

Inflammation is a central component of several chronic human diseases, including atherosclerosis and type 2 diabetes. Several nuclear receptors repress inflammatory responses, but their molecular mechanisms remain poorly understood. The nuclear receptor superfamily is composed of transcription factors that have emerged as key regulators of inflammation and lipid homeostasis. These include the glucocorticoid receptor, which inhibits inflammatory programs of gene expression in response to natural corticosteroids and synthetic anti-inflammatory ligands such as dexamethasone. In addition, peroxisome proliferator-activated receptors and liverXreceptors, in response to endogenous eicosanoids and oxysterols, respectively, modulate transcriptional pathways involved in inflammatory responses and lipid homeostasis.

Animals↗
PubMed2005

Peroxisome proliferator-activated receptors and inflammation.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptors family. PPARs are a family of 3 ligand-activated transcription factors: PPARalpha (NR1C1), PPARbeta/delta (NUC1; NR1C2), and PPARgamma (NR1C3). PPARalpha, -beta/delta, and -gamma are encoded by different genes but show substantial amino acid similarity, especially within the DNA and ligand binding domains. All PPARs act as heterodimers with the 9-cis-retinoic acid receptors (retinoid X receptor; RXRs) and play important roles in the regulation of metabolic pathways, including those of lipid of biosynthesis and glucose metabolism, as well as in a variety of cell differentiation, proliferation, and apoptosis pathways. Recently, there has been a great deal of interest in the involvement of PPARs in inflammatory processes. PPAR ligands, in particular those of PPARalpha and PPARgamma, inhibit the activation of inflammatory gene expression and can negatively interfere with pro-inflammatory transcription factor signaling pathways in vascular and inflammatory cells. Furthermore, PPAR levels are differentially regulated in a variety of inflammatory disorders in man, where ligands appear to be promising new therapies.

Animals↗
PubMed1983

Anaphylactic release of a prekallikrein activator from human lung in vitro.

We have demonstrated the in vitro IgE-mediated release of a prekallikrein activator from human lung. The lung prekallikrein activator was partially purified by sequential chromatography on sulfopropyl-Sephadex, DEAE-Sephacel, and Sepharose 6B. Purified human prekallikrein was converted to its active form (kallikrein) by the lung protease. The generated kallikrein was shown to be biologically active; that is, it generates bradykinin from purified human high-molecular weight kininogen and also cleaves benzoyl-propyl-phenyl-arginyl-p-nitroanilide, a known synthetic substrate of kallikrein. The lung prekallikrein activator differs from the known physiologic activators of prekallikrein (the activated forms of Hageman factor) with respect to: (a) size (it has a mol wt of approximately 175,000); (b) synthetic substrate specificity (D-propyl/phenyl/arginyl-p-nitroanilide is a substrate for the activated forms of Hageman factor, but not the lung protease); (c) antigenic specificity (an anti-Hageman factor immunoadsorbent column did not remove significant amounts of the lung protease, while it removed most of the activity of activated Hageman factor fragments); and (d) inhibition profile (the lung proteases was not inhibited by corn trypsin inhibitor). This prekallikrein activator provides a physiologic mechanism by which prekallikrein can be directly activated during IgE-mediated reactions of the lung. While the role of this lung prekallikrein activator in immediate hypersensitivity reactions and in other inflammatory processes is not clear, it does represent a first and important interface between IgE-mediated reactions and the Hageman factor-dependent pathways of the inflammatory response.

Anaphylaxis↗
PubMed1999

[Expression and its clinical significance of tissue factor pathway inhibitor and antithrombin-III in patients with hepatic inflammatory diseases].

OBJECTIVE: To investigate the change and clinical significance of tissue factor pathway inhibitor (TFPI) and antithrombin-III (AT-III) in the plasma of patients with hepatic inflammatory disease (HID). METHODS: The plasma levels and activation of TFPI and AT-III in patients with HID (Group I, n = 82) were compared to that in healthy people (Group II as control, n = 30). RESULTS: The plasma level of TFPI:Ag in Group I was higher (P < 0.05) and its activation was also increased dramatically (P < 0.01), the level of AT-III: A was lower in patients with chronic hepatitis B (P < 0.05) and no difference was found in other indices between the two groups. CONCLUSIONS: The elevation of TFPI:Ag and TFPI:A in hepatic inflammatory diseases is an indication of inflammation, and hepatic tissue injury in broad, the lower level of AT-III liver secretions.

Adult↗
PubMed2006

Trans fatty acids - effects on systemic inflammation and endothelial function.

Consumption of trans fatty acids (TFA) predicts higher risk of coronary heart disease, sudden death, and possibly diabetes mellitus. These associations are greater than would be predicted by effects of TFA on serum lipoproteins alone. Systemic inflammation and endothelial dysfunction may be involved in the pathogenesis of atherosclerosis, acute coronary syndromes, sudden death, insulin resistance, dyslipidemia, and heart failure. Evidence from both observational and experimental studies indicates that TFA are pro-inflammatory. Limited evidence suggests that pro-inflammatory effects may be stronger for trans isomers of linoleic acid (trans-C18:2) and oleic acid (trans-C18:1), rather than of palmitoleic acid (trans-C16:1), but further study of potential isomer-specific effects is needed. TFA also appear to induce endothelial dysfunction. The mechanisms underlying these effects are not well-established, but may involve TFA incorporation into endothelial cell, monocyte/macrophage, or adipocyte cell membranes (affecting membrane signaling pathway relating to inflammation) or ligand-dependent effects on peroxisome proliferator-activated receptor (PPAR) or retinoid X receptor (RXR) pathways. Activation of inflammatory responses and endothelial dysfunction may represent important mediating pathways between TFA consumption and risk of coronary heart disease, sudden death, and diabetes. Further study is indicated to define these effects of TFA and the implications of such effects for cardiovascular health.

Atherosclerosis↗