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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New horizons in frailty: the contingent, the existential and the clinical

In the past decade, frailty research has focused on refinement of biomedical tools and operationalisations, potentially introducing a reductionist approach. This article suggests that a new horizon in frailty lies in a more holistic approach to health and illness in old age. This would build on approaches that view healthy ageing in terms of functionality, in the sense of intrinsic capacity in interplay with social environment, whilst also emphasising positive attributes. Within this framework, frailty is conceptualised as originating as much in the social as in the biological domain; as co-existing with positive attributes and resilience, and as situated on a continuum with health and illness. Relatedly, social science-based studies involving interviews with, and observations of, frail, older people indicate that the social and biographical context in which frailty arises might be more impactful on the subsequent frailty trajectory than the health crisis which precipitates it. For these reasons, the article suggests that interpretive methodologies, derived from the social sciences and humanities, will be of particular use to the geriatrician in understanding health, illness and frailty from the perspective of the older person. These may be included in a toolkit with the purpose of identifying how biological and social factors jointly underpin the fluctuations of frailty and in designing interventions accordingly. Such an approach will bring clinical approaches closer to the views and experiences of older people who live with frailty, as well as to the holistic traditions of geriatric medicine itself

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

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Endothelium-derived Vasoactive Factors and Hypertension: Possible Roles in Pathogenesis and as Treatment Targets

Endothelial cells regulate vascular tone by releasing various contracting and relaxing factors including nitric oxide (NO), arachidonic acid metabolites (derived from cyclooxygenases, lipoxygenases, and cytochrome P450 monooxygenases), reactive oxygen species, and vasoactive peptides. Additionally, another pathway associated with the hyperpolarization of the underlying smooth muscle cells plays a predominant role in resistance arteries. Endothelial dysfunction is a multifaceted disorder, which has been associated with hypertension of diverse etiologies, involving not only alterations of the L-arginine NO-synthase–soluble guanylyl cyclase pathway but also reduced endothelium-dependent hyperpolarizations and enhanced production of contracting factors, particularly vasoconstrictor prostanoids. This brief review highlights these different endothelial pathways as potential drug targets for novel treatments in hypertension and the associated endothelial dysfunction and end-organ damage

Molecular dissection of the interplay between SIRT1, LKB1 and HERC2: linkage implication in endothelial senescence and vascular remodeling

Symposium Theme: From Molecular Machinery to Clinical ChallengesPoster Session 3: Late Breaking Abstracts & Vendor Exhibits: no. PS3-4: abstract ISRA156Endothelial senescence is one of the earliest events during vascular aging and contributes to vascular remodeling. Sirtuin-1 (SIRT1) elicits its anti-senescent functions in part by mediating proteasome-mediated degradation of LKB1, a pro-senescent protein kinase [1], [2]. The present study was designed to investigate the molecular mechanisms underlying SIRT1-regulated LKB1 degradation by focusing on an E3 ligase, HERC2 (HECT domain and RLD 2 protein). In primary porcine aortic endothelial cells (PAECs), LKB1 degradation was significantly blocked by MG132. Western blotting revealed that LKB1 was ubiquitinated and degraded in nucleus. HERC2 was identified as the E3 ligase of LKB1. Knockdown of HERC2 enhanced the protein accumulation of LKB1 in nucleus and promoted ...postprin