Re-evaluation of dietary interventions in rheumatoid arthritis: can we improve patient conversations around food choices?

Rheumatoid arthritis (RA) is one of over 100 different types of autoimmune conditions. In RA, the cells of the immune system attack the tissue lining the joints, triggering inflammation. A large body of research suggests that the underlying trigger(s) of RA are unique to an individual.

Microbial disruption in the gut promotes cerebral endothelial dysfunction.

Cerebrovascular disease is a group of conditions characterized by disorders of the cerebral vessels. Endothelial dysfunction renders the vasculature at risk of impaired blood flow and increases the potential of developing cerebrovascular disease. The gut microbiota has been recently identified as a possible risk factor of cerebrovascular disease.

Rapamycin induces the expression of heme oxygenase-1 and peroxyredoxin-1 in normal hepatocytes but not in tumorigenic liver cells.

Rapamycin (sirolimus) is employed as an immunosuppressant following liver transplant, to inhibit the re-growth of cancer cells following liver resection for hepatocellular carcinoma (HCC), and for the treatment of advanced HCC. Rapamycin also induces the expression of antioxidant enzymes in the liver, suggesting that pretreatment with the drug could provide a potential strategy to reduce ischemia reperfusion injury following liver surgery. The aim of this study was to further investigate the actions of rapamycin in inducing expression of the antioxidant enzymes heme oxygenase-1 (HO-1) and peroxiredoxin-1 (Prx-1) in normal liver and in tumorigenic liver cells.

Evidence that decreased expression of sinusoidal bile acid transporters accounts for the inhibition by rapamycin of bile flow recovery following liver ischemia.

Rapamycin is employed as an immunosuppressant following organ transplant and, in patients with hepatocellular carcinoma, to inhibit cancer cell regrowth following liver surgery. Preconditioning the liver with rapamycin to induce the expression of antioxidant enzymes is a potential strategy to reduce ischemia reperfusion (IR) injury. However, pre-treatment with rapamycin inhibits bile flow, especially following ischemia.

Relationship between Vascular Resistance and Sympathetic Nerve Fiber Density in Arterial Vessels in Children With Sleep Disordered Breathing.

Background: Sleep disordered breathing in children is associated with increased blood flow velocity and sympathetic overactivity. Sympathetic overactivity results in peripheral vasoconstriction and reduced systemic vascular compliance, which increases blood flow velocity during systole. Augmented blood flow velocity is recognized to promote vascular remodeling.

Proteomic analysis reveals downregulation of housekeeping proteins in the diabetic vascular proteome.

Aims: Type 2 diabetes (T2D) increases the risk of death associated with cardiovascular complications. However, a complete understanding of protein changes within the diabetic vasculature is still lacking.

Methods: Herein, we utilized mass spectrometry to perform vascular and urinary proteome analysis using a rat model of high-fat feeding and low-dose streptozotocin to simulate late-stage T2D.

Differential Telomere Shortening in Blood versus Arteries in an Animal Model of Type 2 Diabetes.

Vascular dysfunction is an early feature of diabetic vascular disease, due to increased oxidative stress and reduced nitric oxide (NO) bioavailability. This can lead to endothelial cell senescence and clinical complications such as stroke. Cells can become senescent by shortened telomeres and oxidative stress is known to accelerate telomere attrition.

Compromised endothelium-dependent hyperpolarization-mediated dilations can be rescued by NS309 in obese Zucker rats.

Objective: NO and a non-NO/prostacyclin EDH mechanism are major contributors of vascular tone and cerebral blood flow. However, the effect of metabolic syndrome on EDH-mediated responses in cerebral vessels remains unknown and may offer another avenue for therapeutic targeting. The purpose of this study was to investigate EDH-dependent responses in cerebral arteries during metabolic syndrome.

Sirtuin 1 is upregulated in young obese Zucker rat cerebral arteries.

Many diseases, including metabolic syndrome, are characterised by endothelial dysfunction mediated by reduced nitric oxide bioavailability and oxidative stress. Sirtuin 1 is a protein deacetylase that targets endothelial nitric oxide synthase resulting in enhanced nitric oxide bioavailability. Although it has been highlighted as a potential therapeutic target, we still have no understanding of vascular SIRT1 changes during obesity.

Regulation of cerebral vascular function by sirtuin 1.

Objective: Endothelial dysfunction, associated with reduced nitric oxide bioavailability and oxidative stress, is a common feature of vascular-related diseases. Sirtuin 1 (SIRT1) is a protein deacetylase that has been shown to target endothelial nitric oxide synthase in large arteries and is protective during oxidative stress. However, within resistance-sized vessels, the expression and functional effects of SIRT1 remain unknown.

Pannexin protein expression in the rat middle cerebral artery.

Background: Connexin proteins are well known to participate in cell-to-cell communication within the cerebral vasculature. Pannexins are a recently discovered family of proteins that could potentially be involved in cell-to-cell communication. Herein, we sought to determine whether pannexins are expressed in rat middle cerebral artery (MCA).

Myoendothelial gap junction frequency does not account for sex differences in EDHF responses in rat MCA.

Previous findings from our laboratory have shown that dilations to endothelium-derived hyperpolarizing factor (EDHF) in rat middle cerebral artery (MCA) are less in females compared to males. Myoendothelial gap junctions (MEGJs) appear to mediate the transfer of hyperpolarization between endothelium and smooth muscle in males. In the present study, we hypothesized that MEGJs are the site along the EDHF pathway which is compromised in female rat MCA.

DCEBIO-mediated dilations are attenuated in the female rat middle cerebral artery.

Background: Unlike in peripheral vessels, the endothelium-derived hyperpolarizing factor (EDHF)-mediated component to P2Y(2) receptor-mediated dilations is significantly attenuated in the middle cerebral artery (MCA) of female rats compared to male rats. One aspect to the EDHF phenomenon is activation of the intermediate calcium-sensitive potassium (IK(Ca)) channels located on the endothelium. In an attempt to pinpoint the site along the EDHF pathway that is compromised in females, we tested the hypothesis that direct activation of IK(Ca) channels with DCEBIO would elicit attenuated hyperpolarization in the endothelium and smooth muscle of females compared to males.

Impaired cAMP signaling does not account for the attenuated EDHF-mediated dilations in female rat middle cerebral artery.

Dilations to endothelium-derived hyperpolarizing factor (EDHF) are significantly attenuated in the middle cerebral artery (MCA) isolated from female compared to male rats. Since gap junctions appear to be involved in the EDHF pathway and cAMP has been shown to enhance gap junction permeability, we tested the hypothesis that elevation of cAMP would enhance EDHF-mediated dilations in female rat MCA. Vascular diameter was measured in perfused MCA segments using videomicroscopy in the presence and absence of IBMX, an inhibitor of cAMP phosphodiesterase.

Endothelium-dependent vasodilation of cerebral arteries is altered with simulated microgravity through nitric oxide synthase and EDHF mechanisms.

Cephalic elevations in arterial pressure associated with microgravity and prolonged bed rest alter cerebrovascular autoregulation in humans. Using the head-down tail-suspended (HDT) rat to chronically induce headward fluid shifts and elevate cerebral artery pressure, previous work has likewise shown cerebral perfusion to be diminished. The purpose of this study was to test the hypothesis that 2 wk of HDT reduces cerebral artery vasodilation.

Evidence for the involvement of myoendothelial gap junctions in EDHF-mediated relaxation in the rat middle cerebral artery.

The mechanisms underlying endothelium-dependent hyperpolarizing factor (EDHF) in the middle cerebral artery (MCA) remain largely unresolved. In particular, very little is known regarding the way in which the signal is transmitted from endothelium to smooth muscle. The present study tested the hypothesis that direct communication via myoendothelial gap junctions contributes to the EDHF response in the male rat MCA.