Vascular fibrosis in aging and hypertension: molecular mechanisms and clinical implications

Aging is the primary risk factor underlying hypertension and incident cardiovascular disease. With aging, the vasculature undergoes structural and functional changes characterized by endothelial dysfunction, wall thickening, reduced distensibility, and arterial stiffening. Vascular stiffness results from fibrosis and extracellular matrix (ECM) remodelling, processes that are associated with aging and are amplified by hypertension. Some recently characterized molecular mechanisms underlying these processes include increased expression and activation of matrix metalloproteinases, activation of transforming growth factor-β1/SMAD signalling, upregulation of galectin-3, and activation of proinflammatory and profibrotic signalling pathways. These events can be induced by vasoactive agents, such as angiotensin II, endothelin-1, and aldosterone, which are increased in the vasculature during aging and hypertension. Complex interplay between the “aging process” and prohypertensive factors results in accelerated vascular remodelling and fibrosis and increased arterial stiffness, which is typically observed in hypertension. Because the vascular phenotype in a young hypertensive individual resembles that of an elderly otherwise healthy individual, the notion of “early” or “premature” vascular aging is now often used to describe hypertension-associated vascular disease. We review the vascular phenotype in aging and hypertension, focusing on arterial stiffness and vascular remodelling. We also highlight the clinical implications of these processes and discuss some novel molecular mechanisms of fibrosis and ECM reorganization

Progenitor cells, bone marrow–derived fibrocytes and endothelial-to-mesenchymal transition: new players in vascular fibrosis

No abstract available

Sheathing and Pay Techniques in the Boa Vista 1 Ship (Lisbon, Portugal)

Between September 2012 and February 2013, archaeological excavations carried out in the riverside area of Lisbon (Portugal) revealed the remains of two wooden ships: Boa Vista 1 (BV1) and Boa Vista 2 (BV2), both dating from the late seventeenth or early eighteenth century. BV1 ship consists of scattered hull timbers which were damaged and out of their original positions. Some of the ship’s hull features are common in the Mediterranean like a composite keel with butt joints and hook scarfs in the connection between floors and futtocks, while others are well-known Iberian shipbuilding features like the transition between the keel and the sternpost being made through a single piece, the heel. A unique feature was a layer of animal hair between the sheathing and the hull planking. This paper focuses mainly on the study of wooden sheathing, including but not limited to the analysis of its conventional “architectural signatures”. The latest results concerning animal hair identification will also be presented and discussed, showing the added value of multidisciplinary approaches in archaeology.info:eu-repo/semantics/publishedVersio

Vascular smooth muscle contraction in hypertension

Hypertension is a major risk factor for many common chronic diseases, such as heart failure, myocardial infarction, stroke, vascular dementia and chronic kidney disease. Pathophysiological mechanisms contributing to the development of hypertension include increased vascular resistance, determined in large part by reduced vascular diameter due to increased vascular contraction and arterial remodelling. These processes are regulated by complex interacting systems such as the renin angiotensin aldosterone system (RAAS), sympathetic nervous system, immune activation and oxidative stress, which influence vascular smooth muscle function. Vascular smooth muscle cells are highly plastic and in pathological conditions undergo phenotypic changes from a contractile to a proliferative state. Vascular smooth muscle contraction is triggered by an increase in intracellular free calcium concentration ([Ca2+]i), promoting actin-myosin cross-bridge formation. Growing evidence indicates that contraction is also regulated by calcium-independent mechanisms involving RhoA-Rho kinase (ROCK), protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) signaling, reactive oxygen species and reorganization of the actin cytoskeleton. Activation of immune/inflammatory pathways and noncoding RNAs are also emerging as important regulators of vascular function. Vascular smooth muscle cell [Ca2+]i, not only determines the contractile state but also influences activity of many calcium-dependent transcription factors and proteins thereby impacting the cellular phenotype and function. Perturbations in vascular smooth muscle cell signaling and altered function influence vascular reactivity and tone, important determinants of vascular resistance and blood pressure. Here we discuss mechanisms regulating vascular reactivity and contraction in physiological and pathophysiological conditions and highlight some new advances in the field, focusing specifically on hypertension

Vascular dysfunction and fibrosis in stroke-prone spontaneously hypertensive rats: the aldosterone-mineralocorticoid receptor-Nox1 Axis

Aims: We questioned whether aldosterone and oxidative stress play a role in vascular damage in severe hypertension and investigated the role of Nox1 in this process. Materials and methods: We studied mesenteric arteries, aortas and vascular smooth muscle cells (VSMC) from WKY and SHRSP rats. Vascular effects of eplerenone or canrenoic acid (CA) (mineralocorticoid receptor (MR) blockers), ML171 (Nox1 inhibitor) and EHT1864 (Rac1/2 inhibitor) were assessed. Nox1-knockout mice were also studied. Vessels and VSMCs were probed for Noxs, reactive oxygen species (ROS) and pro-fibrotic/inflammatory signaling. Key findings: Blood pressure and plasma levels of aldosterone and galectin-3 were increased in SHRSP versus WKY. Acetylcholine-induced vasorelaxation was decreased (61% vs 115%) and phenylephrine-induced contraction increased in SHRSP versus WKY (Emax 132.8% vs 96.9%, p < 0.05). Eplerenone, ML171 and EHT1864 attenuated hypercontractility in SHRSP. Vascular expression of collagen, fibronectin, TGFβ, MCP-1, RANTES, MMP2, MMP9 and p66Shc was increased in SHRSP versus WKY. These changes were associated with increased ROS generation, 3-nitrotyrosine expression and Nox1 upregulation. Activation of vascular p66Shc and increased expression of Nox1 and collagen I were prevented by CA in SHRSP. Nox1 expression was increased in aldosterone-stimulated WKY VSMCs, an effect that was amplified in SHRSP VSMCs (5.2vs9.9 fold-increase). ML171 prevented aldosterone-induced VSMC Nox1-ROS production. Aldosterone increased vascular expression of fibronectin and PAI-1 in wild-type mice but not in Nox1-knockout mice. Significance: Our findings suggest that aldosterone, which is increased in SHRSP, induces vascular damage through MR-Nox1-p66Shc-mediated processes that modulate pro-fibrotic and pro-inflammatory signaling pathways

Prejudice, Vulnerability, Adhesion Process, Religiousness Regarding the Life Routine with AIDS: Life Stories

Objective: To communicate life stories of people who suffer from acquired immunodeficiency-syndrome with a higher vulnerability registered at the Municipal Secretary of Social Assistance and the diagnostic’s influence on their daily routine. Method: Descriptive and exploratory study based on oral life history. Thirteen people with AIDs took part in the study via a semi-structured interview. The narratives were analyzed using Bardin’s thematic content analysis. Results: Three thematic axes emerged from Bardin’s content analysis: prejudice and discrimination regarding the life routine with aids; Reaction when facing the diagnostic and the adhesion process for the antiretroviral treatment; Confrontation of religion and religiousness on people with aids. Conclusion: The people living with aids, a chronic and stigmatizing disease, need the support of multidisciplinary teams and an improvement in relation to the access, the coverage and the meaning assigned to the disease, besides a better quality of life and social assistance. We conclude that religion did not contribute to facing these people’s conditions. It brought blame, incorrect information that may impair the treatment and their follow-up. One infers that health education regarding HIV/AIDS needs to be remodeled on all of society’s segments

Employees’ fit to telework and work well-being: (in)voluntariness in telework as a mediating variable?

Purpose: The present study aims to examine the mediating role of (in)voluntariness in teleworking in explaining the relationship between employees’ fit to telework and work well-being (i.e. work engagement and exhaustion). Design/methodology/approach: A cross-sectional survey design was used in this study. The sample comprised 222 individuals performing telework in Portugal. Statistical analyses employed were descriptive statistics, Pearson’s correlation, confirmatory factor and structural equation analyses, and mediation analysis using Hayes Process macro. Findings: The findings confirmed the hypothesis that employees’ fit to telework raises the voluntariness in telework and decreases involuntariness in telework. However, contrary to expectations, no significant relationships were found between voluntariness in telework, work engagement and exhaustion. Yet, involuntariness in telework showed a significant role in decreasing work engagement and increasing workers’ exhaustion. The mediating role of involuntariness in telework was confirmed in explaining the relationship between employees’ fit to telework and exhaustion. Practical implications: Managers in global firms can draw from the results to understand how employees’ fit to telework directly and/or indirectly contributes to work well-being and develop human resource (HR) management practices aiming to increase employees’ fit to telework. Originality/value: Although teleworking is already studied, to the best of the authors’ knowledge, no studies have analyzed the same conceptual model employees’ fit to telework, (in)voluntariness in teleworking and work well-being.info:eu-repo/semantics/acceptedVersio

Deciphering a multi-event in a non-complex set of detrital zircon U-Pb ages from Carboniferous graywackes of SW Iberia

The determination of U–Pb ages from detrital zircons of sedimentary rocks using LA-ICP-MS has been widely used for the purpose of provenance analysis. One problem that frequently arises is finding a population that appears to be non-complex despite several perceptible age peaks in its spectrum. These peaks are qualitatively defined by means of relative probability diagrams, or PDFs, but it is difficult to quantify their statistical significance relative to a zircon forming multi-event. Thus, can a multi-event in a non-complex set of detrital zircon U–Pb ages be deciphered and characterized? The aim of this study is to attempt to provide an answer to this question by means of statistical analysis. Its objectives are: a) to determine the best minimum number of zircon age populations (peaks), BmPs, b) for the characterization of each peak in terms of age and event duration; c) to compare the results obtained from two datasets showing similar zircon ages; and d) to demonstrate the usefulness of deciphering these BmPs. First, cluster analysis is carried out, aimed at grouping zircon ages into a set of consistent clusters. A Gaussian Kernel function is then fitted to each cluster and summed to obtain a theoretical PDFm (modeled probability density function). Finally, the selected modeled PDFm (that built on the BmPs) is that which reports the lowest number of peaks for which the difference as compared with the original gPDF (global probability density function) is equal to or below 5%. Deciphered BmP peaks can be characterized and used for characterizing and providing an understanding of related event(s). A geological interpretation, based on the results obtained, is attempted. This includes a robust measure for maximum age of deposition for both Cabrela and Mértola graywackes