histone deacetylase hypertension

The modification of N6-methyladenosine (m6A) modification is implicated in human diseases. However, considerable uncertainty is associated with the regulatory mechanisms of m6A circRNAs in coronary artery disease (CAD), which require further clarification. In this study, m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq) was conducted to investigate m6A-modified circRNAs in human coronary artery smooth muscle cells (HCASMCs) and to identify potential biomarkers for CAD. A total of 830 and 331 up- and down-regulated m6A peaks, (corresponding to 463 and 243 up- and down-regulated circRNAs, respectively), were identified in HCASMCs in a pathological condition...

Epigenetics is defined as a heritable change occurring in gene expression and phenotype without altering the underlying primary DNA sequence itself. Epigenetic variation consists of DNA methylation repatterning, posttranslational modification of histone proteins, and non-coding RNAs (ncRNAs). Epigenetic modifications are deeply involved in tumorigenesis and tumor development. Epigenetic abnormalities can be therapeutically reversed, and three families of epigenetic marks, including "readers", "writers" and "erasers", could be modulated by epi drugs...

Vascular endothelial cells (ECs) are monolayer cells located in the inner layer of the blood vessel. Endothelial function is crucial in maintaining local and systemic homeostasis and is precisely regulated by sophisticated signaling pathways and epigenetic regulation. Endothelial dysfunctions are the main factors for the pathophysiological process of cardiovascular and cerebrovascular diseases like atherosclerosis, hypertension, and stroke. In these pathologic processes, histone deacetylases (HDACs) involve in epigenetic regulation by removing acetyl groups from lysine residues of histones and regulating downstream gene expression...

Pulmonary vascular remodeling caused by the excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) is the hallmark feature of pulmonary arterial hypertension (PAH). Eukaryotic initiation factor 3 subunit A (EIF3A) exhibited proliferative activity in multiple cell types. The present study investigated the role of EIF3A in the progression of PAH. A monocrotaline (MCT)-induced PAH rat model was constructed, and adeno-associated virus type 1 (AAV1) carrying EIF3A shRNA was intratracheally delivered to PAH rats to block EIF3A expression...

BACKGROUND: Pulmonary hypertension (PH) is a lethal disease characterized by pulmonary vascular remodeling, which is mediated by the abnormal proliferation/migration of pulmonary arterial smooth muscle cells (PASMCs). Recent reports suggest the involvement of histone acetylation in PAH development and that histone deacetylase (HDAC) inhibitors have therapeutic potential for the treatment of PAH. EP300 is an acetyltransferase that plays diverse roles in cell proliferation, differentiation, and apoptosis...

BACKGROUND: Prenatal exposure to adverse factors can cause congenital heart defects. Ketamine, a widely used anesthetic drug, produces several adverse reactions such as tachycardia, hypertension, and laryngospasm, especially in pediatric patients. This study aimed to detect the effects of ketamine exposure during pregnancy on the cardiogenesis of mouse offspring and the potential mechanisms. METHODS: In this study, ketamine at an addictive dose (5 mg/kg) was administered to mice during early gestation to explore the epigenetic mechanism of its causing cardiac dysplasia...

RATIONALE: Sildenafil, a well-known vasodilator known to interfere with purinergic signaling through effects on cGMP, is a mainstay in the treatment of pulmonary hypertension (PH). However, little is known regarding its effects on the metabolic reprogramming of vascular cells, which is a hallmark of pulmonary hypertension (PH). Purine metabolism, especially intracellular de novo purine biosynthesis is essential for vascular cell proliferation. Since adventitial fibroblasts are critical contributors to proliferative vascular remodeling in pulmonary hypertension, in this study we aimed to investigate if sildenafil, beyond its well-known vasodilator role in smooth muscle cells, impacts intracellular purine metabolism and proliferation of fibroblasts derived from human PH patients...

Poor control of metabolic diseases induces kidney injury, resulting in microalbuminuria, renal insufficiency and, ultimately, chronic kidney disease. The potential pathogenetic mechanisms of renal injury caused by metabolic diseases remain unclear. Tubular cells and podocytes of the kidney show high expression of histone deacetylases known as sirtuins (SIRT1-7). Available evidence has shown that SIRTs participate in pathogenic processes of renal disorders caused by metabolic diseases. The present review addresses the regulatory roles of SIRTs and their implications for the initiation and development of kidney damage due to metabolic diseases...

BACKGROUND: Substantial evidence suggests that hypertension is a significant risk factor for cognitive decline. However, it is unclear whether the genetic predisposition to hypertension is also associated with cellular dysfunction that promotes neurodegeneration. METHODS: Changes in blood pressure were evaluated following dietary salt-loading or administration of a regular diet in Sabra Normotensive (SBN/y) and Sabra Hypertension-prone rats (SBH/y). We performed quantitative RT-PCR and immunofluorescence staining in brain cortical tissues before salt loading and 6 and 9 months after salt loading...

Silent information regulator 1 (SIRT1), a highly conserved NAD+ -dependent deacetylase, is a cellular regulator that has received extensive attention in recent years and regarded as a sensor of cellular energy and metabolism. The accumulated evidence suggests that SIRT1 is involved in the development of endocrine and metabolic diseases. In a variety of organisms, SIRT1 regulates gene expression through the deacetylation of histone, transcription factors, and lysine residues of other modified proteins including several metabolic and endocrine signal transcription factors, thereby enhancing the therapeutic effects of endocrine and metabolic diseases...

BACKGROUND: Overproduction of endothelial extracellular vesicles (eEVs) is correlated with pulmonary hypertension progression, but the precise mechanism remains largely unclear. METHODS: MicroRNA-chip and real-time polymerase chain reaction real-time polymerase chain reaction were conducted to screen and validate microRNA profiles in blood plasma eEVs of rats and human with or without cigarette smoking. Pulmonary artery smooth muscle cells were cultured to study signaling pathways...

PURPOSE: Pregnancy-induced hypertension (PIH) is a major cause of mortality among pregnant women, fetuses, and newborns. This study assessed the role of long noncoding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) in PIH development. METHODS: Serum samples were collected from 30 pregnant women with PIH and 30 healthy pregnant women. Serum UCA1, miR-197-3p, and histone deacetylase-2 (HDAC2) mRNA level was evaluated using quantitative polymerase chain reaction...

BACKGROUND/AIMS: Acute kidney injury (AKI) is common, results in nonrenal sequelae, and predisposes patients to long-term cardiovascular disease. The long-term systemic effects of AKI remain unclear. Sex is an important biological variable in ischemia-reperfusion AKI, and the protective role of estrogen has stymied the inclusion of both sexes in preclinical AKI studies. ITF2357 is a nonspecific histone deacetylase inhibitor that has been shown to improve cardiac outcomes in murine models of hypertension...

BACKGROUND: Angiotensin AT2 -receptor signaling is atypical for a G-protein coupled receptor and incompletely understood. To obtain novel insights into AT2 -receptor signaling, we mapped changes in the phosphorylation status of the entire proteome of human aortic endothelial cells in response to AT2 -receptor stimulation. METHODS: Phosphorylation status of human aortic endothelial cells after stimulation with C21 (1 µM; 0, 1, 3, 5, 20 minutes) was determined utilizing time-resolved quantitative phosphoproteomics...

Metabolic syndrome (MetS) is a pathological condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Sirtuin 1 (SIRT1), a highly conserved histone deacetylase, is characterized as a key metabolic regulator and protector against aging-associated pathologies, including MetS. In this study, we investigate the therapeutic potential of activating SIRT1 using small activating RNAs (saRNA), thereby reducing inflammatory-like responses and re-establishing normal lipid metabolism...

BACKGROUND: Heart failure (HF) coincides with cardiomyocyte telomere shortening. Arterial hypertension is the most prominent risk factor for HF. Both HF and arterial hypertension are associated with dysregulation of the neurohormonal axis. How neurohormonal activation is linked to telomere shortening in the pathogenesis of HF is incompletely understood. METHODS: Cardiomyocyte telomere length was assessed in a mouse model of hypertensive HF induced by excess neurohormonal activation (AngII [angiotensin II] infusion, high-salt diet, and uninephrectomy), in AngII-stimulated cardiomyocytes and in endomyocardial biopsies from patients with HF...

Aging is a key risk factor for angiogenic dysfunction and cardiovascular diseases, including heart failure, hypertension, atherosclerosis, diabetes, and stroke. Members of the NAD+ -dependent class III histone deacetylase family, sirtuins, are conserved regulators of aging and cardiovascular and cerebrovascular diseases. The sirtuin SIRT6 is predominantly located in the nucleus and shows deacetylase activity for acetylated histone 3 lysine 56 and lysine 9 as well as for some non-histone proteins. Over the past decade, experimental analyses in rodents and non-human primates have demonstrated the critical role of SIRT6 in extending lifespan...

Salt-inducible kinases (SIKs) are serine/threonine kinases belonging to the AMP-activated protein kinase (AMPK) family. Accumulating evidence indicates that SIKs phosphorylate multiple targets, including histone deacetylases (HDACs) and cAMP response element-binding protein (CREB)-regulated transcriptional coactivators (CRTCs), to coordinate signaling pathways implicated in metabolism, cell growth, proliferation, apoptosis, and inflammation. These pathways downstream of SIKs are altered not only in pathologies like cancer, systemic hypertension, and inflammatory diseases, but also in pulmonary arterial hypertension (PAH), a multifactorial disease characterized by pulmonary vasoconstriction, inflammation and remodeling of pulmonary arteries owing to endothelial dysfunction and aberrant proliferation of smooth muscle cells (SMCs)...

Cardiovascular diseases are a group of diseases with high morbidity and mortality that affect millions of people each year. Vascular calcification (VC) is an active process that involves the mineral deposition of calcium-phosphate complexes. VC is closely related to cardiovascular diseases, such as hypertension, heart failure, and calcific aortic stenosis, and is a type of ectopic calcification that occurs in the vessel walls. The sirtuins (silent mating-type information regulation 2; SIRTs), are a family of histone deacetylases whose function relies on nicotinamide adenine dinucleotide (NAD+)...

Systemic sclerosis (SSc) is the most common connective tissue disease causing pulmonary hypertension (PAH). However, the cause and potential immune molecular events associated with PAH are still unclear. Therefore, it is particularly essential to analyze the changes in SSc-PAH-related immune cells and their immune-related genes. Three microarray datasets (GSE22356, GSE33463, and GSE19617) were obtained by the Gene Expression Omnibus (GEO). Compared with SSc, we found neutrophils have a statistically higher abundance, while T-cell CD4 naive and T-cell CD4 memory resting have a statistically lower abundance in peripheral blood mononuclear cells (PBMCs)...