Comparison of the protein acetylome of endothelial cells upon shear flow and resveratrol treatment

Background: Posttranslational acetylation/deacetylation known as the acetylome is important in regulating protein activity. Shear flow (SF) and resveratrol (RSV) are two stimuli that represent physical and chemical signal separately. The acetylome co-regulated by these two stimuli remain unclear. Methods: Human umbilical cord vein endothelial cells (HUVECs) were subjected to either SF of 12 dynes/cm2 or 10 μM RSV. The purified acetylated peptides were labeled by isobaric tags for relative and absolute quantitation (iTRAQ) analysis. The signaling cascades of the identified acetylome were predicted by ingenuity pathway analysis (IPA). Co-immunoprecipitation was applied to confirm the acetylation status of proteins. Results: Five groups of proteins showed an increased acetylation upon SF and RSV treatment. After algorithm, 628 proteins with increased acetylation and 22 proteins with decreased acetylation were identified in the SF acetylome. For the acetylome regulated by RSV, 145 proteins with increased acetylation and 23 proteins with decreased acetylation were identified. Compared these two acetylomes, 129 proteins with increased acetylation and 2 proteins with decreased acetylation were co-regulated by both SF and RSV treatments. IPA analysis showed that this co-regulated acetylome was involved in heat shock response, and the signals of eNOS, STAT3, JAK/STAT and ERK/MAPK. Co-immunoprecipitation analysis further confirmed the acetylated status of mitochondrial HSP60 and mitochondrial citrate synthase. Conclusions: This study indicated that physical signal is more complicated than chemical signal in the case of acetylome. The co-regulated proteins are worthy for further study in discussing synergetic effect between physical and chemical signal in cardioprotection

Oxidative stress and epigenetic regulation in ageing and age-related diseases

Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations is, therefore, of the highest relevance for the development of new treatments for age-associated diseases, such as cancer, diabetes, Alzheimer and cardiovascular accidents. Mechanistically, it is well accepted that the accumulation of intracellular damage determined by reactive oxygen species (ROS) might orchestrate the progressive loss of control over biological homeostasis and the functional impairment typical of aged tissues. Here, we review how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology. Alteration of epigenetic enzyme activity, histone modifications and DNA-methylation is, in fact, typically associated with the ageing process. Specifically, ageing presents peculiar epigenetic markers that, taken altogether, form the still ill-defined “ageing epigenome”. The comprehension of mechanisms and pathways leading to epigenetic modifications associated with ageing may help the development of anti-ageing therapies

Розширення тканин як стимулятор ангіогенезу

Ангіогенез - це процес утворення нових судин у тканинах і органах за участі багатьох факторів. На ангіогенез можуть впливати різноманітні фактори, такі як механічне розтягування тканин, гіпоксія, інфекція, запалення тощо. Розуміння цих механізмів може мати важливе значення для розроблення нових підходів до лікування різних захворювань, пов’язаних із порушенням ангіогенезу. Процес ангіогенезу відіграє важливу роль у різних фізіологічних і патологічних станах, таких як зцілення ран, регенерація тканин, розвиток пухлин та інші. Регулювання ангіогенезу може бути використане для лікування хвороб, пов’язаних із нестачею кровообігу. Знання про ангіогенез також можуть бути корисними в плануванні та проведенні операцій, для підвищення ефективності операції, що може допомогти значно зменшити ризик ускладнень та уникнути повторного втручання. Мета - провести пошук і аналіз останніх публікацій для визначення тенденції розвитку напрямів впливу на ріст судин. Пошук публікацій здійснено у загально відомих світових наукометричних базах даних, діапазон яких охоплював понад 10 років. Знайдено та проаналізовано опубліковані результати багаторічних досліджень, фактори та методи впливу на ангіогенез. На сьогодні питання впливу на ангіогенез залишаються відкритими, що викликає потребу подальшого дослідження та вивчення нових методів і удосконалення існуючих, оскільки знання про механізми ангіогенезу можуть допомогти розробити нові методи лікування й профілактики різних захворювань. Автори заявляють про відсутність конфлікту інтересів

Perioperative Implication of the Endothelial Glycocalyx

The endothelial glycocalyx (EG) is a gel-like layer lining the luminal surface of healthy vascular endothelium. Recently, the EG has gained extensive interest as a crucial regulator of endothelial funtction, including vascular permeability, mechanotransduction, and the interaction between endothelial and circulating blood cells. The EG is degraded by various enzymes and reactive oxygen species upon pro-inflammatory stimulus. Ischemia-reperfusion injury, oxidative stress, hypervolemia, and systemic inflammatory response are responsible for perioperative EG degradation. Perioperative damage of the EG has also been demonstrated, especially in cardiac surgery. However, the protection of the EG and its association with perioperative morbidity needs to be elucidated in future studies. In this review, the present knowledge about EG and its perioperative implication is discussed from an anesthesiologist\u27s perspective

SIRT6 protects against endothelial dysfunction and atherosclerosis in mice

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SIRT1 and AMPK in regulating mammalian senescence: A critical review and a working model

Ageing in mammals remains an unsolved mystery. Anti-ageing is a recurring topic in the history of scientific research. Lifespan extension evoked by Sir2 protein in lower organisms has attracted a large amount of interests in the last decade. This review summarizes recent evidence supporting the role of a Sir2 mammalian homologue, SIRT1 (Silent information regulator T1), in regulating ageing and cellular senescence. The various signaling networks responsible for the anti-ageing and anti-senescence activity of SIRT1 have been discussed. In particular, a counter-balancing model involving the cross-talks between SIRT1 and AMP-activated protein kinase (AMPK), another stress and energy sensor, is suggested for controlling the senescence program in mammalian © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reservedcells.postprin

Laminar Shear Stress Protects Against Premature Endothelial Senescence by SIRT1-Dependent Mechanisms

Abstracts PURPOSE Accumulation of senescent endothelial cells (ECs) and development of vascular aging have been implicated in the etiology of vascular dysfunction and disease. Aerobic exercise has been recognized as the single most effective non-pharmacological anti-aging intervention via increased laminar shear stress (LSS). This study aimed to determine the protective effects of LSS against premature senescence and the underlying mechanism. METHODS Carotid artery partial ligation surgery was performed on the left carotid arteries (LCAs) of C57BL/6J male mice to determine the effect of disturbed flow on the development of endothelial senescence. Senescence-associated β-galactosidase (SA-β-gal) staining was performed to measure cellular senescence. Expression levels of protein markers for cell senescence including p21, p16, and p53 were measured by western blotting. RESULTS En face SA-β-gal staining was identified only in the partially ligated LCAs of voluntary wheel-running mice, suggesting a direct relevance of LSS on the prevention of vascular senescence. In the in vitro H2 O2-induced premature senescence model, preconditioning of high-flow LSS (20 dyne/cm2, 36 hours) induced significant reduction in the percentage of SA-β-gal positive ECs. Expression of the molecular markers of cellular senescence such as p21, p16, and p53 was significantly decreased by LSS pretreatment. However, the protective effects of LSS against premature senescence were completely abolished by SIRT1 inhibition. CONCLUSIONS The results suggest that high-flow LSS has protective effects against oxidative stress-induced premature endothelial senescence through a SIRT1-dependent mechanism

Role of Hdac3 in Murine Coronary Vessel Development: A Master\u27s Thesis

Coronary vessel development is a crucial part of heart development requiring the interplay of the epicardial, myocardial and endocardial layers of the heart for proper formation. Coronary vascularization is regulated by a host of transcription factors further regulated by chromatin remodeling enzymes, including Histone Deacetylases (HDACs). To investigate the functions of HDACs in coronary vascular development, we have deleted Hdac3 in endocardial cells using Cre LoxP technology. Endocardial cell-­‐specific deletion of Hdac3 results in aberrant coronary vessel formation and complete postnatal lethality. We have thus shown that Hdac3 is a critical regulator of the coronary vascular development pathway

Phenolic bioactives as antiplatelet aggregation factors: the pivotal ingredients in maintaining cardiovascular health

Cardiovascular diseases (CVD) are one of the main causes of mortality in the world. The development of these diseases has a specific factor—alteration in blood platelet activation. It has been shown that phenolic compounds have antiplatelet aggregation abilities and a positive impact in the management of CVD, exerting prominent antioxidant, anti-inflammatory, antitumor, cardioprotective, antihyperglycemic, and antimicrobial effects. Thus, this review is intended to address the antiplatelet activity of phenolic compounds with special emphasis in preventing CVD, along with the mechanisms of action through which they are able to prevent and treat CVD. In vitro and in vivo studies have shown beneficial effects of phenolic compound-rich plant extracts and isolated compounds against CVD, despite that the scientific literature available on the antiplatelet aggregation ability of phenolic compounds in vivo is scarce. Thus, despite the current advances, further studies are needed to confirm the cardioprotective potential of phenolic compounds towards their use alone or in combination with conventional drugs for effective therapeutic interventions.N.C.-M. acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017).info:eu-repo/semantics/publishedVersio

Epigenetic Signatures in Arterial Hypertension: Focus on the Microvasculature

Systemic arterial hypertension (AH) is a multifaceted disease characterized by accelerated vascular aging and high cardiometabolic morbidity and mortality. Despite extensive work in the field, the pathogenesis of AH is still incompletely understood, and its treatment remains challenging. Recent evidence has shown a deep involvement of epigenetic signals in the regulation of transcriptional programs underpinning maladaptive vascular remodeling, sympathetic activation and cardiometabolic alterations, all factors predisposing to AH. After occurring, these epigenetic changes have a long-lasting effect on gene dysregulation and do not seem to be reversible upon intensive treatment or the control of cardiovascular risk factors. Among the factors involved in arterial hypertension, microvascular dysfunction plays a central role. This review will focus on the emerging role of epigenetic changes in hypertensive-related microvascular disease, including the different cell types and tissues (endothelial cells, vascular smooth muscle cells and perivascular adipose tissue) as well as the involvement of mechanical/hemodynamic factors, namely, shear stress