The endothelial saga: The past, the present, the future

Endothelium-dependent changes in vasomotor tone, whether evoked by vasoactive agents or physical forces, are recognized as essential for the local hemodynamic control in various normal and pathological circumstances. They are based on a complex signaling network within the vascular wall. In recent years, substantial efforts have been made to analyze how such signals are generated and used in the endothelium-dependent control of vascular smooth muscle. The underlying mechanisms vary with species, age, sex, hormonal status, vascular bed studied, caliber of the blood vessels, triggering stimuli, pre-existing vascular tone, oxidative stress, and pathology. Such aspects and many others will be addressed specifically by the authors contributing to this volume. © 2010 Springer-Verlag.postprin

CDK5-mediated phosphorylation of SIRT1 at serine 47 contributes to the development of endothelial senescence

ISA 2012 Monday AbstractsPoster Session 1 – Vascular Biology of Atherosclerosis: Poster no. 98: Monday abstract no. 206BACKGROUND: Senescence of endothelial cells precedes the occurrence of vascular dysfunction and promotes the development of atherosclerosis. SIRT1 is a NAD-dependent deacetylase possessing anti-aging activities. In senescent endothelial cells, both the activity and expression level of SIRT1 are decreased. However, mechanisms underlying this down-regulation of SIRT1 are largely uncharacterized. The present study evaluated the regulation and role of ...postprintThe 16th International Symposium on Atherosclerosis (ISA2012), Sydney, Australia, 25-29 March 2012. In ISA2012 Monday Abstract

Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium

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Disruption of COX-2 and eNOS does not confer protection from cardiovascular failure in lipopolysaccharide-treated conscious mice and isolated vascular rings

It was hypothesized that a serial stimulation of vascular cyclooxygenase-2 (COX-2) with subsequent activation of endothelial nitric oxide synthase (eNOS) is responsible for decrease in blood pressure, cardiac performance, and vascular reactivity in endotoxemia caused by LPS. The hypothesis was tested in catheterized, conscious, freely moving, wild-type mice and mice (C57BL/6J background) with targeted deletion of COX-2 and eNOS that were given an intravenous LPS bolus (2 mg/kg, 055:B5). In vitro studies were performed on murine aorta rings. LPS caused a concomitant decrease in mean arterial blood pressure (MAP) and heart rate (HR) that was significant after 3 h and was sustained throughout the experiment (8 h). The LPS-induced changes in MAP and HR were not different from control in COX-2−/− and eNOS−/− mice. A prostacyclin receptor antagonist (BR5064) blocked the hypotensive effect of a prostacyclin agonist (beraprost), but did not attenuate the LPS-induced decrease in MAP and HR. LPS decreased eNOS and neuronal NOS mRNA abundances in several organs, while inducible NOS mRNA was enhanced. In aortic rings, LPS suppressed α1-adrenoceptor-mediated vascular tone. Inhibition of COX-2 activity (NS 398), disruption of COX-2, endothelium removal, or eNOS deletion (eNOS−/−) did not improve vascular reactivity after LPS, while the NO synthase blockers 1400W and NG-nitro-l-arginine methyl ester prevented loss of tone. COX-2 and eNOS activities are not necessary for LPS-induced decreases in blood pressure, heart rate, and vascular reactivity. Inducible NOS activity appears crucial. COX-2 and eNOS are not obvious therapeutic targets for cardiovascular rescue during gram-negative endotoxemic shock. </jats:p

Deamidated lipocalin-2 induces endothelial dysfunction and hypertension in dietary obese mice

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Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus

Age, ageing and subjective wellbeing in later life

Objectives. This paper examines age-related changes in subjective wellbeing in later life using multiple measures that cover eudemonic, evaluative and affectivedimensions of wellbeing.Method. Using data from five waves of the English Longitudinal Study of Ageing(2002-2011), we fit multilevel linear growth curve models to examine the crosssectional effects of age and the longitudinal effects of ageing on quality of life,depressive symptomatology and life satisfaction in later life.Results. Older individuals are shown to have a better subjective wellbeing than those that are younger for each wellbeing measure, except at the oldest age for quality of life. Nonetheless, deterioration in wellbeing is greater at older ages, even when adjusting for age-related changes in later life, including widowhood, retirement and declining health.Discussion. The results suggest that although older people enjoy higher levels ofsubjective wellbeing than their younger counterparts, they experience sharper declines, especially at the oldest ages. The findings also demonstrate the importance of taking into account the multidimensionality of subjective wellbeing to determine the point at which age deterioration begins to occur across different measures