scholarly journals The Role of Histone Protein Acetylation in Regulating Endothelial Function

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhi Fang ◽  
Xiang Wang ◽  
Xiaoran Sun ◽  
Wenquan Hu ◽  
Qing R. Miao
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Histone Acetylation ◽  
Transcriptional Unit ◽  
Epigenetic Mark ◽  
Protein Acetylation ◽  
Status Change ◽  
Histone Protein ◽  
Protein Coding ◽  
Physiological Processes

Endothelial cell (EC), consisting of the innermost cellular layer of all types of vessels, is not only a barrier composer but also performing multiple functions in physiological processes. It actively controls the vascular tone and the extravasation of water, solutes, and macromolecules; modulates circulating immune cells as well as platelet and leukocyte recruitment/adhesion and activation. In addition, EC also tightly keeps coagulation/fibrinolysis balance and plays a major role in angiogenesis. Therefore, endothelial dysfunction contributes to the pathogenesis of many diseases. Growing pieces of evidence suggest that histone protein acetylation, an epigenetic mark, is altered in ECs under different conditions, and the acetylation status change at different lysine sites on histone protein plays a key role in endothelial dysfunction and involved in hyperglycemia, hypertension, inflammatory disease, cancer and so on. In this review, we highlight the importance of histone acetylation in regulating endothelial functions and discuss the roles of histone acetylation across the transcriptional unit of protein-coding genes in ECs under different disease-related pathophysiological processes. Since histone acetylation changes are conserved and reversible, the knowledge of histone acetylation in endothelial function regulation could provide insights to develop epigenetic interventions in preventing or treating endothelial dysfunction-related diseases.

Abstract 14318: Long Noncoding RNA Differentiation Antagonizing Non-protein Coding RNA 201 Ameliorates Endothelial Dysfunction via Sponging MicroRNA-216a

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
rongxia li ◽  
Shujun Yang ◽  
Yu Chen ◽  
Weili Zhang
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Noncoding Rna ◽  
Protective Factor ◽  
Luciferase Assay ◽  
Protein Coding ◽  
Control Subjects ◽  
Vulnerable Plaques ◽  
And Control

Background: Endothelial dysfunction contributes to the initiation of atherosclerosis, which has been associated with the long noncoding RNAs (lncRNAs). However, the role of lncRNAs in endothelial function remains largely unknown. This study aimed to investigate whether the differentiation antagonizing non-protein coding RNA 201 (DANCR201) regulated the endothelial function. Methods and Results: The whole transcriptome sequencing was conducted to identify differentially expressed lncRNAs in the peripheral blood from patients with coronary artery diseases who had coronary calcified plaques (n=10), vulnerable plaques (n=5), and control subjects without coronary plaques (n=10). The characteristics of plaques were determined by the coronary computed tomography angiography. The results showed that DANCR201 was significantly downregulated in patients with vulnerable plaques compared to those with calcified plaques and control subjects. The RNA fluorescence in situ hybridization showed that DANCR201 was localized in both cytoplasm and nuclei. Next, we assessed the role of DANCR201 in endothelial function. In the replicative aging model of human umbilical vein endothelial cells (HUVECs), DANCR201 was found to decrease in senescent passage 20 cells compared with young passage 3 cells. Furthermore, DANCR201 overexpression in HUVECs significantly repressed monocytes adhesion to endothelium, inhibited the expression of pro-inflammatory cytokines interleukin 1β, intercellular cell adhesion molecule 1, tumor necrosis factor α, and promoted the abilities of endothelial proliferation and migration, indicating that DANCR201 was a protective factor for endothelial function. Bioinformatics analysis of miRNA-lncRNA interactions indicated that DANCR201 contained a candidate binding sequence of miR-216a which had been reported to promote the endothelial dysfunction through NF-κB pathway. The luciferase assay further showed that DANCR201 specifically combined with miR-216a. Conclusions: Our data indicated that DANCR201 can improve endothelial function via sponging miR-216a, ultimately maintaining vascular normalization. DANCR201 maybe a potential therapeutic target for atherosclerotic plaque progression and instability.

scholarly journals The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

2022 ◽  
Vol 27 (1) ◽  
Author(s):  
Hongjuan You ◽  
Qi Li ◽  
Delong Kong ◽  
Xiangye Liu ◽  
Fanyun Kong ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Protein Function ◽  
Protein Modification ◽  
Epigenetic Modification ◽  
Lysine Acetylation ◽  
Protein Acetylation ◽  
Post Translational Modification ◽  
Histone Protein ◽  
Protein Lysine Acetylation ◽  
Canonical Wnt

AbstractCanonical Wnt/β-catenin signaling is a complex cell-communication mechanism that has a central role in the progression of various cancers. The cellular factors that participate in the regulation of this signaling are still not fully elucidated. Lysine acetylation is a significant protein modification which facilitates reversible regulation of the target protein function dependent on the activity of lysine acetyltransferases (KATs) and the catalytic function of lysine deacetylases (KDACs). Protein lysine acetylation has been classified into histone acetylation and non-histone protein acetylation. Histone acetylation is a kind of epigenetic modification, and it can modulate the transcription of important biological molecules in Wnt/β-catenin signaling. Additionally, as a type of post-translational modification, non-histone acetylation directly alters the function of the core molecules in Wnt/β-catenin signaling. Conversely, this signaling can regulate the expression and function of target molecules based on histone or non-histone protein acetylation. To date, various inhibitors targeting KATs and KDACs have been discovered, and some of these inhibitors exert their anti-tumor activity via blocking Wnt/β-catenin signaling. Here, we discuss the available evidence in understanding the complicated interaction of protein lysine acetylation with Wnt/β-catenin signaling, and lysine acetylation as a new target for cancer therapy via controlling this signaling.

Coronary Artery Disease and Endothelial Dysfunction: Novel Diagnostic and Therapeutic Approaches

2020 ◽  
Vol 27 (7) ◽  
pp. 1052-1080 ◽  
Author(s):  
Evangelos Oikonomou ◽  
Gerasimos Siasos ◽  
Vasiliki Tsigkou ◽  
Evanthia Bletsa ◽  
Maria-Evi Panoilia ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Stable Coronary Artery Disease ◽  
Therapeutic Interventions ◽  
Therapeutic Approaches ◽  
Cardiovascular Prognosis ◽  
Ultrasound Evaluation ◽  
Artery Disease

Coronary artery disease is the leading cause of morbidity and mortality worldwide. The most common pathophysiologic substrate is atherosclerosis which is an inflammatory procedure that starts at childhood and develops throughout life. Endothelial dysfunction is associated with the initiation and progression of atherosclerosis and is characterized by the impaired production of nitric oxide. In general, endothelial dysfunction is linked to poor cardiovascular prognosis and different methods, both invasive and non-invasive, have been developed for its evaluation. Ultrasound evaluation of flow mediated dilatation of the branchial artery is the most commonly used method to assessed endothelial function while intracoronary administration of vasoactive agents may be also be used to test directly endothelial properties of the coronary vasculature. Endothelial dysfunction has also been the subject of therapeutic interventions. This review article summarizes the knowledge about evaluation of endothelial function in acute coronary syndromes and stable coronary artery disease and demonstrates the current therapeutic approaches against endothelial dysfunction.

Therapeutic Potential of Phosphodiesterase Inhibitors for Endothelial Dysfunction- Related Diseases

2020 ◽  
Vol 26 (30) ◽  
pp. 3633-3651 ◽  
Author(s):  
Javier Blanco-Rivero ◽  
Fabiano E. Xavier
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
Phosphodiesterase Inhibitors ◽  
Developed Countries ◽  
Major Health Problem ◽  
Pde Inhibitors ◽  
Pharmaceutical Industries

Cardiovascular diseases (CVD) are considered a major health problem worldwide, being the main cause of mortality in developing and developed countries. Endothelial dysfunction, characterized by a decline in nitric oxide production and/or bioavailability, increased oxidative stress, decreased prostacyclin levels, and a reduction of endothelium-derived hyperpolarizing factor is considered an important prognostic indicator of various CVD. Changes in cyclic nucleotides production and/ or signalling, such as guanosine 3', 5'-monophosphate (cGMP) and adenosine 3', 5'-monophosphate (cAMP), also accompany many vascular disorders that course with altered endothelial function. Phosphodiesterases (PDE) are metallophosphohydrolases that catalyse cAMP and cGMP hydrolysis, thereby terminating the cyclic nucleotide-dependent signalling. The development of drugs that selectively block the activity of specific PDE families remains of great interest to the research, clinical and pharmaceutical industries. In the present review, we will discuss the effects of PDE inhibitors on CVD related to altered endothelial function, such as atherosclerosis, diabetes mellitus, arterial hypertension, stroke, aging and cirrhosis. Multiple evidences suggest that PDEs inhibition represents an attractive medical approach for the treatment of endothelial dysfunction-related diseases. Selective PDE inhibitors, especially PDE3 and PDE5 inhibitors are proposed to increase vascular NO levels by increasing antioxidant status or endothelial nitric oxide synthase expression and activation and to improve the morphological architecture of the endothelial surface. Thereby, selective PDE inhibitors can improve the endothelial function in various CVD, increasing the evidence that these drugs are potential treatment strategies for vascular dysfunction and reinforcing their potential role as an adjuvant in the pharmacotherapy of CVD.

Magnesium intake, insulin resistance and markers of endothelial function among women

2021 ◽  
pp. 1-9
Author(s):  
Narges Ghorbani Bavani ◽  
Parvane Saneei ◽  
Ammar Hassanzadeh Keshteli ◽  
Ahmadreza Yazdannik ◽  
Ebrahim Falahi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Adhesion Molecule ◽  
Cell Function ◽  
Intercellular Adhesion Molecule ◽  
Model Assessment ◽  
Serum Concentrations ◽  
Homeostasis Model Assessment

Abstract Objective: We investigated the association of dietary Mg intake with insulin resistance and markers of endothelial function among Iranian women. Design: A cross-sectional study. Setting: Usual dietary intakes were assessed using a validated FFQ. Dietary Mg intake was calculated by summing up the amount of Mg in all foods. A fasting blood sample was taken to measure serum concentrations of glycemic indices (fasting plasma glucose and insulin) and endothelial function markers (E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1). Insulin resistance and sensitivity were estimated using the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), Homeostasis Model Assessment β-cell function (HOMA-β) and quantitative insulin sensitivity check index (QUICKI). Participants: Iranian female nurses (n 345) selected by a multistage cluster random sampling method. Results: The Mg intake across energy-adjusted quartiles was 205 (se 7), 221·4 (se 8), 254·3 (se 7) and 355·2 (se 9) mg/d, respectively. After adjustments for potential confounders, QUICKI level was significantly different across quartiles of Mg intake (Q1: 0·34 (se 0·02), Q2: 0·36 (se 0·01), Q3: 0·40 (se 0·01), and Q4: 0·39 (se 0·02), P = 0·02); however, this association disappeared after considering markers of endothelial function, indicating that this relation might be mediated through endothelial dysfunction. After controlling for all potential confounders, Mg intake was inversely, but not significantly, associated with serum concentrations of sICAM (Q1: 239 (se 17), Q2: 214 (se 12), Q3: 196 (se 12), and Q4: 195 (se 17), P = 0·29). There was no other significant association between dietary Mg intake and other indicators of glucose homoeostasis or endothelial markers. Conclusions: Higher dietary Mg intake was associated with better insulin sensitivity in Iranian females. This linkage was mediated through reduced endothelial dysfunction.

scholarly journals The Leucine Catabolite and Dietary Supplement β-Hydroxy-β-Methyl Butyrate (HMB) as an Epigenetic Regulator in Muscle Progenitor Cells

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 512
Author(s):  
Virve Cavallucci ◽  
Giovambattista Pani
Keyword(s):  
Histone Acetylation ◽  
Dietary Supplement ◽  
Hdac Inhibitor ◽  
Muscle Wasting ◽  
C2c12 Cells ◽  
Myoblast Differentiation ◽  
Epigenetic Mark ◽  
Epigenetic Regulator ◽  
Methyl Butyrate

β-Hydroxy-β-Methyl Butyrate (HMB) is a natural catabolite of leucine deemed to play a role in amino acid signaling and the maintenance of lean muscle mass. Accordingly, HMB is used as a dietary supplement by sportsmen and has shown some clinical effectiveness in preventing muscle wasting in cancer and chronic lung disease, as well as in age-dependent sarcopenia. However, the molecular cascades underlying these beneficial effects are largely unknown. HMB bears a significant structural similarity with Butyrate and β-Hydroxybutyrate (βHB), two compounds recognized for important epigenetic and histone-marking activities in multiple cell types including muscle cells. We asked whether similar chromatin-modifying actions could be assigned to HMB as well. Exposure of murine C2C12 myoblasts to millimolar concentrations of HMB led to an increase in global histone acetylation, as monitored by anti-acetylated lysine immunoblotting, while preventing myotube differentiation. In these effects, HMB resembled, although with less potency, the histone deacetylase (HDAC) inhibitor Sodium Butyrate. However, initial studies did not confirm a direct inhibitory effect of HMB on HDACs in vitro. β-Hydroxybutyrate, a ketone body produced by the liver during starvation or intense exercise, has a modest effect on histone acetylation of C2C12 cells or in vitro HDAC inhibitor activities, and, unlike Butyrate and HMB, did not interfere with myotube formation in a myoblast differentiation assay. Instead, βHB dramatically increased lysine β-hydroxybutyrylation (Kbhb) of histone tails, an epigenetic mark associated with fasting responses and muscle catabolic states. However, when C2C12 cells were exposed to βHB in the presence of equimolar HMB this chromatin modification was drastically reduced, pointing to a role for HMB in attenuating ketosis-associated muscle wasting. In conclusion, while their mechanistic underpinnings remain to be clarified, these preliminary observations highlight novel and potentially important activities of HMB as an epigenetic regulator and βHB antagonist in muscle precursor cells, to be further explored in their biomedical implications.

scholarly journals Comparison of biomarkers of endothelial dysfunction and microvascular endothelial function in patients with primary aldosteronism and essential hypertension

2021 ◽  
Vol 22 (1) ◽  
pp. 147032032199949
Author(s):  
Miaomiao Sang ◽  
Yu Fu ◽  
Chenmin Wei ◽  
Jing Yang ◽  
Xueting Qiu ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Primary Aldosteronism ◽  
Cardiovascular Events ◽  
Statistical Significance ◽  
Enzyme Linked Immunosorbent Assay ◽  
Microvascular Endothelial ◽  
Pai 1 ◽  
Microvascular Endothelial Function

Introduction: Studies have shown that primary aldosteronism (PA) has a higher risk of cardiovascular events than essential hypertension (EH). Endothelial dysfunction is an independent predictor of cardiovascular events. Whether PA and EH differ in the endothelial dysfunction is uncertain. Our study was designed to investigate the levels of biomarkers of endothelial dysfunction (Asymmetric dimethylarginine, ADMA; E-selectin, and Plasminogen activator inhibitor-1, PAI-1) and assess the microvascular endothelial function in patients with PA and EH, respectively. Methods: The biomarkers of endothelial dysfunction were measured by enzyme-linked immunosorbent assay (ELISA). Microvascular endothelial function was evaluated by Pulse amplitude tonometry (PAT). Results: Thirty-one subjects with EH and 36 subjects with PA including 22 with aldosterone-producing adenoma (APA) and 14 with idiopathic hyperaldosteronism (IHA) were enrolled in our study. The ADMA levels among the three groups were different (APA 47.83 (27.50, 87.74) ng/ml vs EH 25.08 (22.44, 39.79) ng/ml vs IHA 26.00 (22.23, 33.75) ng/ml; p = 0.04), however, when the APA group was compared with EH and IHA group, there was no statistical significance (47.83 (27.50, 87.74) ng/ml vs 25.08 (22.44, 39.79) ng/ml for EH, p = 0.11; 47.83 (27.50, 87.74) ng/ml vs IHA 26.00 (33.75) ng/ml, p = 0.07). The results of ADMA levels are presented as Median (p25, p75). Whereas, levels of PAI-1 and E-selectin, microvascular endothelial function were not significantly different between PA and EH subjects. Conclusions: Our study shows no significant differences between PA and EH in terms of biomarkers of endothelial dysfunction and microvascular endothelial function. The microvascular endothelial function of PA and EH patients is comparable.

scholarly journals Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review

2015 ◽  
Vol 36 (1) ◽  
pp. 72-94 ◽  
Author(s):  
Anna Poggesi ◽  
Marco Pasi ◽  
Francesca Pescini ◽  
Leonardo Pantoni ◽  
Domenico Inzitari
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Small Vessel Disease ◽  
Brain Magnetic Resonance Imaging ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
Brain Changes

The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes.

scholarly journals Rabbit somatic cell cloning: effects of donor cell type, histone acetylation status and chimeric embryo complementation

Reproduction ◽  
2007 ◽  
Vol 133 (1) ◽  
pp. 219-230 ◽  
Author(s):  
Feikun Yang ◽  
Ru Hao ◽  
Barbara Kessler ◽  
Gottfried Brem ◽  
Eckhard Wolf ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Nuclear Transfer ◽  
Donor Cell ◽  
Epigenetic Mark ◽  
Cell Type ◽  
Developmental Potential ◽  
Acetylation Status ◽  
Donor Cells ◽  
Donor Cell Type

The epigenetic status of a donor nucleus has an important effect on the developmental potential of embryos produced by somatic cell nuclear transfer (SCNT). In this study, we transferred cultured rabbit cumulus cells (RCC) and fetal fibroblasts (RFF) from genetically marked rabbits (Alicia/Basilea) into metaphase II oocytes and analyzed the levels of histone H3-lysine 9-lysine 14 acetylation (acH3K9/14) in donor cells and cloned embryos. We also assessed the correlation between the histone acetylation status of donor cells and cloned embryos and their developmental potential. To test whether alteration of the histone acetylation status affects development of cloned embryos, we treated donor cells with sodium butyrate (NaBu), a histone deacetylase inhibitor. Further, we tried to improve cloning efficiency by chimeric complementation of cloned embryos with blastomeres fromin vivofertilized or parthenogenetic embryos. The levels of acH3K9/14 were higher in RCCs than in RFFs (P<0.05). Although the type of donor cells did not affect development to blastocyst, after transfer into recipients, RCC cloned embryos induced a higher initial pregnancy rate as compared to RFF cloned embryos (40 vs 20%). However, almost all pregnancies with either type of cloned embryos were lost by the middle of gestation and only one fully developed, live RCC-derived rabbit was obtained. Treatment of RFFs with NaBu significantly increased the level of acH3K9/14 and the proportion of nuclear transfer embryos developing to blastocyst (49 vs 33% with non-treated RFF,P<0.05). The distribution of acH3K9/14 in either group of cloned embryos did not resemble that inin vivofertilized embryos suggesting that reprogramming of this epigenetic mark is aberrant in cloned rabbit embryos and cannot be corrected by treatment of donor cells with NaBu. Aggregation of embryos cloned from NaBu-treated RFFs with blastomeres fromin vivoderived embryos improved development to blastocyst, but no cloned offspring were obtained. Two live cloned rabbits were produced from this donor cell type only after aggregation of cloned embryos with a parthenogenetic blastomere. Our study demonstrates that the levels of histone acetylation in donor cells and cloned embryos correlate with their developmental potential and may be a useful epigenetic mark to predict efficiency of SCNT in rabbits.

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