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Nathan Goodyear

Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk - 0 views

  • Weight gain has been associated with a higher gut permeability
  • a high-fat diet promotes LPS absorption
  • higher concentrations of fatty acids impair intestinal barrier integrity
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  • The starting point for innate immunity activation is the recognition of conserved structures of bacteria, viruses, and fungal components through pattern-recognition receptors
  • TLRs are PRRs that recognize microbe-associated molecular patterns
  • TLRs are transmembrane proteins containing extracellular domains rich in leucine repeat sequences and a cytosolic domain homologous to the IL1 receptor intracellular domain
  • The major proinflammatory mediators produced by the TLR4 activation in response to endotoxin (LPS) are TNFα, IL1β and IL6, which are also elevated in obese and insulin-resistant patients
  • Obesity, high-fat diet, diabetes, and NAFLD are associated with higher gut permeability leading to metabolic endotoxemia.
  • Probiotics, prebiotics, and antibiotic treatment can reduce LPS absorption
  • LPS promotes hepatic insulin resistance, hypertriglyceridemia, hepatic triglyceride accumulation, and secretion of pro-inflammatory cytokines promoting the progression of fatty liver disease.
  • In the endothelium, LPS induces the expression of pro-inflammatory, chemotactic, and adhesion molecules, which promotes atherosclerosis development and progression.
  • In the adipose tissue, LPS induces adipogenesis, insulin resistance, macrophage infiltration, oxidative stress, and release of pro-inflammatory cytokines and chemokines.
  • the gut microbiota has been recently proposed to be an environmental factor involved in the control of body weight and energy homeostasis by modulating plasma LPS levels
  • dietary fats alone might not be sufficient to cause overweight and obesity, suggesting that a bacterially related factor might be responsible for high-fat diet-induced obesity.
  • This was accompanied in high-fat-fed mice by a change in gut microbiota composition, with reduction in Bifidobacterium and Eubacterium spp.
  • n humans, it was also shown that meals with high-fat and high-carbohydrate content (fast-food style western diet) were able to decrease bifidobacteria levels and increase intestinal permeability and LPS concentrations
  • it was demonstrated that, more than the fat amount, its composition was a critical modulator of ME (Laugerette et al. 2012). Very recently, Mani et al. (2013) demonstrated that LPS concentration was increased by a meal rich in saturated fatty acids (SFA), while decreased after a meal rich in n-3 polyunsaturated fatty acids (n-3 PUFA).
  • this effect seems to be due to the fact that some SFA (e.g., lauric and mystiric acids) are part of the lipid-A component of LPS and also to n-3 PUFA's role on reducing LPS potency when substituting SFA in lipid-A
  • these experimental results suggest a pivotal role of CD14-mediated TLR4 activation in the development of LPS-mediated nutritional changes.
  • This suggests a link between gut microbiota, western diet, and obesity and indicates that gut microbiota manipulation can beneficially affect the host's weight and adiposity.
  • endotoxemia was independently associated with energy intake but not fat intake in a multivariate analysis
  • in vitro that endotoxemia activates pro-inflammatory cytokine/chemokine production via NFκB and MAPK signaling in preadipocytes and decreased peroxisome proliferator-activated receptor γ activity and insulin responsiveness in adipocytes.
  • T2DM patients have mean values of LPS that are 76% higher than healthy controls
  • LPS-induced release of glucagon, GH and cortisol, which inhibit glucose uptake, both peripheral and hepatic
  • LPSs also seem to induce ROS-mediated apoptosis in pancreatic cells
  • Recent evidence has been linking ME with dyslipidemia, increased intrahepatic triglycerides, development, and progression of alcoholic and nonalcoholic fatty liver disease
  • The hepatocytes, rather than hepatic macrophages, are the cells responsible for its clearance, being ultimately excreted in bile
  • All the subclasses of plasma lipoproteins can bind and neutralize the toxic effects of LPS, both in vitro (Eichbaum et al. 1991) and in vivo (Harris et al. 1990), and this phenomenon seems to be dependent on the number of phospholipids in the lipoprotein surface (Levels et al. 2001). LDL seems to be involved in LPS clearance, but this antiatherogenic effect is outweighed by its proatherogenic features
  • LPS produces hypertriglyceridemia by several mechanisms, depending on LPS concentration. In animal models, low-dose LPS increases hepatic lipoprotein (such as VLDL) synthesis, whereas high-dose LPS decreases lipoprotein catabolism
  • When a dose of LPS similar to that observed in ME was infused in humans, a 2.5-fold increase in endothelial lipase was observed, with consequent reduction in total and HDL. This mechanism may explain low HDL levels in ‘ME’ and other inflammatory conditions such as obesity and metabolic syndrome
  • It is known that the high-fat diet and the ‘ME’ increase intrahepatic triglyceride accumulation, thus synergistically contributing to the development and progression of alcoholic and NAFLD, from the initial stages characterized by intrahepatic triglyceride accumulation up to chronic inflammation (nonalcoholic steatohepatitis), fibrosis, and cirrhosis
  • On the other hand, LPS activates Kupffer cells leading to an increased production of ROS and pro-inflammatory cytokines like TNFα
  • high-fat diet mice presented with ME, which positively and significantly correlated with plasminogen activator inhibitor (PAI-1), IL1, TNFα, STAMP2, NADPHox, MCP-1, and F4/80 (a specific marker of mature macrophages) mRNAs
  • prebiotic administration reduces intestinal permeability to LPS in obese mice and is associated with decreased systemic inflammation when compared with controls
  • Cani et al. also found that high-fat diet mice presented with not only ME but also higher levels of inflammatory markers, oxidative stress, and macrophage infiltration markers
  • This suggests that important links between gut microbiota, ME, inflammation, and oxidative stress are implicated in a high-fat diet situation
  • high-fat feeding is associated with adipose tissue macrophage infiltration (F4/80-positive cells) and increased levels of chemokine MCP-1, suggesting a strong link between ME, proinflammatory status, oxidative stress, and, lately, increased CV risk
  • LPS has been shown to promote atherosclerosis
  • markers of systemic inflammation such as circulating bacterial endotoxin were elevated in patients with chronic infections and were strong predictors of increased atherosclerotic risk
  • As a TLR4 ligand, LPS has been suggested to induce atherosclerosis development and progression, via a TLR4-mediated inflammatory state.
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    Very nice updated review on Metabolic endotoxemia
Nathan Goodyear

Frontiers | Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of... - 0 views

  • lipopolysaccharides (LPS), either alone or in combination, have indicated that when compared, bacterial LPSs exhibit the strongest induction of pro-inflammatory signaling in human neuronal–glial cells in primary coculture of any single inducer, and different LPS extracts from different gastrointestinal (GI)-tract resident Gram-negative bacteria appeared to have different pro-inflammatory potential
  • powerful inducer of the NF-κB
  • In both neocortex and hippocampus, LPS has been detected to range from a ~7- to ~21-fold increase abundance in AD brain
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  • Major Gram-negative bacilli of the human GI-tract, such as the abundant B. fragilis and Escherichia coli (E. coli), are capable of discharging a remarkably complex assortment of pro-inflammatory neurotoxins
  • (i) bacterial amyloids (10, 21); (ii) endotoxins and exotoxins (5, 12); (iii) LPS (12, 18); and (iv) small non-coding RNAs (sncRNAs)
  • integral components of the outer leaflet of the outer membrane of Gram-negative bacteria, LPS
  • LPS, the major molecular component of the outer membrane of Gram-negative bacteria normally serves as a physical barrier providing the bacteria protection from its surroundings
  • LPS is also recognized by the immune system as a marker for the detection of bacterial pathogen invasion and responsible for the development of inflammatory response is perhaps the most potent stimulator and trigger of inflammation known
  • AD-affected brains have remarkably large loads of bacterial-derived toxins compared to controls. The transfer of noxious, pro-inflammatory molecules from the GI-tract microbiome to the CNS may be increasingly important during the course of aging when both the GI-tract and blood–brain barriers become significantly more permeable
  • first evidence of a perinuclear association of LPS with AD brain cell nuclei
  • LPS-mediated stimulation of chronic inflammation, beta-amyloid accumulation, and episodic memory decline in murine models of AD (39, 40) and a biophysical association of LPS with amyloid deposits and blood vessels in human AD patients
  • Strong adherence of LPS to the nuclear periphery has recently been shown to inhibit nuclear maturation and function that may impair or block export of mRNA signals from brain cell nuclei, a highly active organelle with extremely high rates of transcription, mRNA processing, and export into the cytoplasm
  • LPS may be further injurious to the nuclear membrane just as LPS contributes to cerebrovascular endothelial cell membrane injury
  • high intake of dietary fiber is a strong inhibitor of B. fragilis abundance and proliferation in the intact human GI-tract and as such is a potent inhibitor of the neurotoxic B. fragilis-derived amyloids, LPS, enterotoxins, and sncRNAs.
  • GI-tract microbiome-derived LPS may be an important initiator and/or significant contributor to inflammatory degeneration in the AD CNS
  • LPS has been recently localized to the same anatomical regions involved in AD-type neuropathology
  • a known pro-inflammatory transcription factor complex that triggers the expression of pathogenic pathways involved in neurodegenerative inflammation
  • pro-inflammatory amyloids, endo- and exotoxins, LPSs, and sncRNAs but also serve as potent sources of membrane-disrupting agents
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    LPS links gut to inflammation in Alzheimer's disease
Nathan Goodyear

Chronic exposure to Low dose bacterial lipopolysaccharide inhibits leptin signaling in ... - 0 views

  • Obesity and models of obesity induced by ingestion of HF-diet in rodents are associated with chronically elevated circulating levels of LPS
  • chronic low-dose administration of LPS induces leptin-resistance in vagal afferent neurons and abolition of CCK-induced inhibition of food intake
  • HF fat feeding has been shown to enhance gastrointestinal permeability promoting the translocation of LPS to the circulation
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  • LPS leads to an increase in SOCS3 expression [20]. SOCS3 is a negative regulator of leptin signaling
  • We observed a significant increase in energy intake in the LPS-treated rats
  • the data provides a mechanism linking changes in gut microbiota induced by ingestion of HF diets to dysregulation of food intake and body weight
  • SOCS3 is an important mechanism by which leptin resistance develops in vagal afferent neurons and coincides with the onset of hyperphagia
  • Chronic low-dose LPS treatment induced TLR4 activation and MyD88 signaling in vagal afferent neurons, associated with increased SOCS3 expression and reduced leptin-signaling, characterized by the absence of leptin-induced pSTAT3.
  • We demonstrate that this chronic low dose LPS is sufficient to induce leptin–resistance in vagal afferent neurons, reduced sensitivity to the satiating effects of CCK, and loss of vagal afferent plasticity
  • it suggests that the increase in food intake and body weight we observed at week 6 in the LPS treated rats may be caused by LPS-induced leptin resistance.
  • chronic LPS treatment of mice for four weeks increased body weight
  • chronic LPS treatment of mice for four weeks increased subcutaneous fat
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    Very interesting study.  High fat diet in rats induced gut flora change that resulted in LPS which induced appetite through leptin resistance and reduced cholecystokinin signaling.
Nathan Goodyear

Lipoprotein(a) as a cardiovascular risk factor: current status - 0 views

  • Lipoprotein(a) is a plasma lipoprotein consisting of a cholesterol-rich LDL particle with one molecule of apolipoprotein B100 and an additional protein, apolipoprotein(a)
  • Elevated Lp(a) levels can potentially increase the risk of CVD (i) via prothrombotic/anti-fibrinolytic effects as apolipoprotein(a) possesses structural homology with plasminogen and plasmin but has no fibrinolytic activity and (ii) via accelerated atherogenesis as a result of intimal deposition of Lp(a) cholesterol, or both
  • evidence suggests that apolipoprotein(a) adducts extracellularly and covalently to apolipoprotein B100-containing lipoproteins, predominantly LDL
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  • Lp(a) is relatively refractory to both lifestyle and drug intervention.
  • Other agents reported to decrease Lp(a) to a minor degree (<10%) include aspirin, l-carnitine, ascorbic acid combined with l-lysine, calcium antagonists, angiotensin-converting enzyme inhibitors, androgens, oestrogen, and its replacements (e.g. tibolone), anti-estrogens (e.g. tamoxifen), and thyroxine replacement in hypothyroid subjects
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    full article on the previously posted abstract on Lp(a).  
Nathan Goodyear

Lipoprotein(a), Hormone Replacement Therapy and Risk of Future Cardiovascular Events - 0 views

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    study finds HT reduced Lp(a) in women and reduced the Lp(a) association with CVD.  Women not on HT in this study had higher Lp(a) versus those on HT.
Nathan Goodyear

Plant-Based Nutritional Supplementation Attenuates LPS-Induced Low-Grade Systemic Activ... - 0 views

  • consumption of this particular diet for at least a 2-month period helped to reduce the outcomes of both acute and chronic inflammation induced by LPS.
  • chronic inflammation compromised both glucose and insulin tolerance, which is normally seen in certain chronic metabolic diseases
  • LPS resulted in an increase in neopterin levels, which is a marker for immune system activation
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  • diet enriched in fruits and vegetables (and consequently phytochemicals) was able to reverse the process and maintain and even elevate insulin sensitivity and glucose tolerance
  • LPS-mediated effects are related to an increase in TLR4 levels that triggers the activation of nuclear factor-kB (NF-kB), a transcription factor that activates a cascade of inflammatory mediators [41]. These factors control the transcription of inflammatory mediators, such as IL-1β, IL-6, TNF-α, TNF-β, INF-α, INFβ, INF-γ
  • Inflammation can alter insulin action and give rise to diabetes and obesity by blocking insulin receptor downstream events, impairing insulin receptor substrate 1 (IRS-1) activation and phosphatidylinositol 3-kinase-dependent (PI3K) pathways, therefore compromising insulin signaling
  • systemic inflammation (generated by LPS) also increased neopterin levels in the urine and resulted in altered neuronal activity by decreasing dopamine (DA) metabolism
  • an increase in neopterin levels has been recognized a sensitive biomarker for immune system activation
  • Our experiments denoted that these diets were able to diminish inflammatory mediators and oxidative damage
Nathan Goodyear

Targeting gut microbiota in obesity: effects of prebiotics and probiotics : Article : N... - 0 views

  • gut microbes have a role in the host's metabolic homeostasis
  • lipopolysaccharide (LPS)
  • Associations between circulating LPS level, consumption of a high-fat diet and the presence of obesity and type 2 diabetes mellitus have been confirmed in humans
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  • associations have been proposed between high-fat diet, metabolic endotoxemia and levels of inflammatory markers (TLRs and SOCS3) in mononuclear cells
  • A link between energy intake (high-fat diet) and metabolic endotoxemia has also been described
  • high-fat diet induces metabolic endotoxemia in healthy individuals.
  • metabolic endotoxemia is associated with systemic and adipose tissue inflammation in pregnant women with obesity
  • A growing amount of evidence indicates that changes in the integrity of the intestinal barrier occur both in the proximal and the distal part of the gut, which can contribute to the entrance of LPS into the systemic circulation
  • intestinal endocannabinoid system
  • The low-grade systemic inflammation that characterizes the obese phenotype is controlled by peptides that are produced in the gut. These peptides are influenced by the presence or absence of the gut microbiota
  • these findings suggest that the gut microbiota modulates the biological systems that regulate the availability of nutrients, energy storage, fat mass development and inflammation in the host, which are all components of the obese phenotype
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    good look of how the the gut health, or lack there of, can influence energy homeostasis and contribute to obesity.  This article points to the presence of LPS playing a role in metabolic endotoxemia.  It does discuss the importance of the microbiota and their possible role in the low-grade systemic inflammation condition that is obesity.
Nathan Goodyear

Plasma lipoproteins are important components of the immune system - Han - 2010 - Microb... - 0 views

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    Is all cholesterol bad?  Of course not.  We have got to get away from the linear thinking that plagues medicine.  This article proposes and supports  a protective claim of lipoproteins: VLDL, LDL, Lp(a), and HDL.  Even shown to protect against bacterial, viral, LPS, and parasitic infectious damage.
Nathan Goodyear

Effects of lowering elevated LDL cholesterol on the car... [JAMA. 1995] - PubMed - NCBI - 0 views

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    Lp(a) is a distinct lipoprotein from from LDL.  An Lp(a) is a distinct cardiovascular  biomarker risk.
Nathan Goodyear

Gut Endotoxin Leading to a Decline IN Gonadal function (GELDING) - a novel theory for t... - 0 views

  • GELDING theory (Gut Endotoxin Leading to a Decline IN Gonadal function)
  • trans-mucosal passage of bacterial lipopolysaccharide (LPS) from the gut lumen into the circulation is a key inflammatory trigger underlying male hypogonadism
  • Obesity and a high fat/high calorie diet are both reported to result in changes to gut bacteria and intestinal wall permeability, leading to the passage of bacterial endotoxin (lipopolysaccharide- LPS) from within the gut lumen into the circulation (metabolic endotoxaemia), where it initiates systemic inflammation.
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  • Endotoxin is known to reduce testosterone production by the testis, both by direct inhibition of Leydig cell steroidogenic pathways and indirectly by reducing pituitary LH drive, thereby also leading to a decline in sperm production.
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    Ever heard of the GELDING theory?  This involves the link between LPS endotoxin from the gut and low Testosterone in obese men.
Nathan Goodyear

ScienceDirect - Atherosclerosis : Lipoprotein(a) associated with coronary artery diseas... - 0 views

  • elevated Lp(a) was associated with a significantly increased risk of CAD in men and women
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    elevated Lp(a) associated with a significant increased risk of CAD in both men and women
Nathan Goodyear

Testosterone: a vascular hormone in health and disease - 0 views

  • Testosterone has beneficial effects on several cardiovascular risk factors, which include cholesterol, endothelial dysfunction and inflammation
  • In clinical studies, acute and chronic testosterone administration increases coronary artery diameter and flow, improves cardiac ischaemia and symptoms in men with chronic stable angina and reduces peripheral vascular resistance in chronic heart failure.
  • testosterone is an L-calcium channel blocker and induces potassium channel activation in vascular smooth muscle cells
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  • Animal studies have consistently demonstrated that testosterone is atheroprotective, whereas testosterone deficiency promotes the early stages of atherogenesis
  • there is no compelling evidence that testosterone replacement to levels within the normal healthy range contributes adversely to the pathogenesis of CVD (Carson & Rosano 2011) or prostate cancer (Morgentaler & Schulman 2009)
  • bidirectional effect between decreased testosterone concentrations and disease pathology exists as concomitant cardiovascular risk factors (including inflammation, obesity and insulin resistance) are known to reduce testosterone levels and that testosterone confers beneficial effects on these cardiovascular risk factors
  • Achieving a normal physiological testosterone concentration through the administration of testosterone replacement therapy (TRT) has been shown to improve risk factors for atherosclerosis including reducing central adiposity and insulin resistance and improving lipid profiles (in particular, lowering cholesterol), clotting and inflammatory profiles and vascular function
  • It is well known that impaired erectile function and CVD are closely related in that ED can be the first clinical manifestation of atherosclerosis often preceding a cardiovascular event by 3–5 years
  • no decrease in the response (i.e. no tachyphylaxis) of testosterone and that patient benefit persists in the long term.
  • free testosterone levels within the physiological range, has been shown to result in a marked increase in both flow- and nitroglycerin-mediated brachial artery vasodilation in men with CAD
  • Clinical studies, however, have revealed either small reductions of 2–3 mm in diastolic pressure or no significant effects when testosterone is replaced within normal physiological limits in humans
  • Endothelium-independent mechanisms of testosterone are considered to occur primarily via the inhibition of voltage-operated Ca2+ channels (VOCCs) and/or activation of K+ channels (KCs) on smooth muscle cells (SMCs)
  • Testosterone shares the same molecular binding site as nifedipine
  • Testosterone increases the expression of endothelial nitric oxide synthase (eNOS) and enhances nitric oxide (NO) production
  • Testosterone also inhibited the Ca2+ influx response to PGF2α
  • one of the major actions of testosterone is on NO and its signalling pathways
  • In addition to direct effects on NOS expression, testosterone may also affect phosphodiesterase type 5 (PDE5 (PDE5A)) gene expression, an enzyme controlling the degradation of cGMP, which acts as a vasodilatory second messenger
  • the significance of the action of testosterone on VSMC apoptosis and proliferation in atherosclerosis is difficult to delineate and may be dependent upon the stage of plaque development
  • Several human studies have shown that carotid IMT (CIMT) and aortic calcification negatively correlate with serum testosterone
  • t long-term testosterone treatment reduced CIMT in men with low testosterone levels and angina
  • neither intracellular nor membrane-associated ARs are required for the rapid vasodilator effect
  • acute responses appear to be AR independent, long-term AR-mediated effects on the vasculature have also been described, primarily in the context of vascular tone regulation via the modulation of gene transcription
  • Testosterone and DHT increased the expression of eNOS in HUVECs
  • oestrogens have been shown to activate eNOS and stimulate NO production in an ERα-dependent manner
  • Several studies, however, have demonstrated that the vasodilatory actions of testosterone are not reduced by aromatase inhibition
  • non-aromatisable DHT elicited similar vasodilation to testosterone treatment in arterial smooth muscle
  • increased endothelial NOS (eNOS) expression and phosphorylation were observed in testosterone- and DHT-treated human umbilical vein endothelial cells
  • Androgen deprivation leads to a reduction in neuronal NOS expression associated with a decrease of intracavernosal pressure in penile arteries during erection, an effect that is promptly reversed by androgen replacement therapy
  • Observational evidence suggests that several pro-inflammatory cytokines (including interleukin 1β (IL1β), IL6, tumour necrosis factor α (TNFα), and highly sensitive CRP) and serum testosterone levels are inversely associated in patients with CAD, T2DM and/or hypogonadism
  • patients with the highest IL1β concentrations had lower endogenous testosterone levels
  • TRT has been reported to significantly reduce TNFα and elevate the circulating anti-inflammatory IL10 in hypogonadal men with CVD
  • testosterone treatment to normalise levels in hypogonadal men with the MetS resulted in a significant reduction in the circulating CRP, IL1β and TNFα, with a trend towards lower IL6 compared with placebo
  • parenteral testosterone undecanoate, CRP decreased significantly in hypogonadal elderly men
  • Higher levels of serum adiponectin have been shown to lower cardiovascular risk
  • Research suggests that the expression of VCAM-1, as induced by pro-inflammatory cytokines such as TNFα or interferon γ (IFNγ (IFNG)) in endothelial cells, can be attenuated by treatment with testosterone
  • Testosterone also inhibits the production of pro-inflammatory cytokines such as IL6, IL1β and TNFα in a range of cell types including human endothelial cells
  • decreased inflammatory response to TNFα and lipopolysaccharide (LPS) in human endothelial cells when treated with DHT
  • The key to unravelling the link between testosterone and its role in atherosclerosis may lay in the understanding of testosterone signalling and the cross-talk between receptors and intracellular events that result in pro- and/or anti-inflammatory actions in athero-sensitive cells.
  • testosterone functions through the AR to modulate adhesion molecule expression
  • pre-treatment with DHT reduced the cytokine-stimulated inflammatory response
  • DHT inhibited NFκB activation
  • DHT could inhibit an LPS-induced upregulation of MCP1
  • Both NFκB and AR act at the transcriptional level and have been experimentally found to be antagonistic to each other
  • As the AR and NFκB are mutual antagonists, their interaction and influence on functions can be bidirectional, with inflammatory agents that activate NFκB interfering with normal androgen signalling as well as the AR interrupting NFκB inflammatory transcription
  • prolonged exposure of vascular cells to the inflammatory activation of NFκB associated with atherosclerosis may reduce or alter any potentially protective effects of testosterone
  • DHT and IFNγ also modulate each other's signalling through interaction at the transcriptional level, suggesting that androgens down-regulate IFN-induced genes
  • (Simoncini et al. 2000a,b). Norata et al. (2010) suggest that part of the testosterone-mediated atheroprotective effects could depend on ER activation mediated by the testosterone/DHT 3β-derivative, 3β-Adiol
  • TNFα-induced induction of ICAM-1, VCAM-1 and E-selectin as well as MCP1 and IL6 was significantly reduced by a pre-incubation with 3β-Adiol in HUVECs
  • 3β-Adiol also reduced LPS-induced gene expression of IL6, TNFα, cyclooxygenase 2 (COX2 (PTGS2)), CD40, CX3CR1, plasminogen activator inhibitor-1, MMP9, resistin, pentraxin-3 and MCP1 in the monocytic cell line U937 (Norata et al. 2010)
  • This study suggests that testosterone metabolites, other than those generated through aromatisation, could exert anti-inflammatory effects that are mediated by ER activation.
  • The authors suggest that DHT differentially effects COX2 levels under physiological and pathophysiological conditions in human coronary artery smooth muscle cells and via AR-dependent and -independent mechanisms influenced by the physiological state of the cell
  • There are, however, a number of systematic meta-analyses of clinical trials of TRT that have not demonstrated an increased risk of adverse cardiovascular events or mortality
  • The TOM trial, which was designed to investigate the effect of TRT on frailty in elderly men, was terminated prematurely as a result of an increased incidence of cardiovascular-related events after 6 months in the treatment arm
  • trials of TRT in men with either chronic stable angina or chronic cardiac failure have also found no increase in either cardiovascular events or mortality in studies up to 12 months
  • Evidence may therefore suggest that low testosterone levels and testosterone levels above the normal range have an adverse effect on CVD, whereas testosterone levels titrated to within the mid- to upper-normal range have at least a neutral effect or, taking into account the knowledge of the beneficial effects of testosterone on a series of cardiovascular risk factors, there may possibly be a cardioprotective action
  • The effect of testosterone on human vascular function is a complex issue and may be dependent upon the underlying androgen and/or disease status.
  • the majority of studies suggest that testosterone may display both acute and chronic vasodilatory effects upon various vascular beds at both physiological and supraphysiological concentrations and via endothelium-dependent and -independent mechanisms
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    Good deep look into the testosterone and CVD link.
Nathan Goodyear

Curcumin abrogates LPS-induced proinflammatory cytokines in RAW 264.7 macrophages. Evid... - 0 views

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    Curcumin is a potent inhibitor of LPS induced inflammation in cell line. Particularily, PGE2, IL-6, and TNF-alpha were inhibited in a dose dependent manner form 5microM to 30 microM.
Nathan Goodyear

Purple Carrot Anthocyanins Decrease LPS Stimulated Nitric Oxide Production - 0 views

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    Anthocyanins decrease LPS stimulated NO production in a dose dependent manner.
Nathan Goodyear

Metformin Inhibits the Production of Reactive Oxygen Species from NADH:Ubiqui... - 0 views

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    Metformin inhibits LPS induced IL-1beta stimulation.  Interesting that metformin is a inhibitor of complex I in the electron transport chain.
Nathan Goodyear

UCL Discovery - EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: Ev... - 0 views

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    Omega 3, DHA and EPA, reduce LPS stimulated inflammation via PPAR gamma activation.
Nathan Goodyear

EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: Evidence... - 0 views

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    Omega 3 essential fatty acids, specifically EPA and DHA, decrease LPS activation of NF-kappaB via PPAR-gamma activation.
Nathan Goodyear

Inhibition of nitric oxide and inflammatory cytokines in LPS-stimulated murine macropha... - 0 views

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    In addition to quercetin, resveratrol and pterostilbene inhibit LPS stimulated cytokine production.
Nathan Goodyear

Abstract 3608: Lipoprotein (a) Cholesterol, But Not Lp(a) Mass, Is An Independent Predi... - 0 views

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    Lipoprotein (a) cholesterol is a better predictor of CAD and CVD events than Lipoprotein (a) mass.
Nathan Goodyear

American College of Cardiology Foundation | Journal of the American College of Cardiolo... - 0 views

  • Lp(a) is a circulating lipoprotein composed of liver-derived apo(a) covalently bound to apoB, which is similar in lipid composition to apoB of LDL
  • multiple studies have shown that elevated Lp(a) levels are independently and linearly predictive of future CVD
  • higher levels were continuously related to risk of myocardial infarction.
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    good discussion of Lipoprotein(a) and its associated cardiovascular risk.
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