histone deacetylase cardiovascular

Histone deacetylases (HDACs) are epigenetic modifying enzyme that is closely related to chromatin structure and gene transcription, and numerous studies have found that HDACs play an important regulatory role in atherosclerosis disease. Apoptosis, autophagy and programmed necrosis as the three typical programmed cell death modalities that can lead to cell loss and are closely related to the developmental process of atherosclerosis. In recent years, accumulating evidence has shown that the programmed cell death mediated by HDACs is increasingly important in the pathophysiology of atherosclerosis...

Supramolecular chemistry offers new insights in bioimaging, but specific tracking of enzyme in living cells via supramolecular host-guest reporter pair remains challenging, largely due to the interference caused by the complex cellular environment on the binding between analytes and hosts. Here, by exploiting the principle of supramolecular tandem assay (STA) and the classic host-guest reporter pair (p-sulfonatocalix[4]arene (SC4A) and lucigenin (LCG)) and rationally designing artificial peptide library to screen sequence with high affinity of the target enzyme, we developed a "turn-on" fluorescent sensing system for intracellular imaging of histone deacetylase 1 (HDAC1), which is a potential therapeutic target for various diseases, including cancer, neurological, and cardiovascular diseases...

Sirtuins belong to the class III histone deacetylases and possess nicotinamide adenine dinucleotide-dependent deacetylase activity. They are involved in the regulation of multiple signaling pathways implicated in cardiovascular diseases. Autophagy is a crucial adaptive cellular response to stress stimuli. Mounting evidence suggests a strong correlation between Sirtuins and autophagy, potentially involving cross-regulation and crosstalk. Sirtuin-mediated autophagy plays a crucial regulatory role in some cardiovascular diseases, including atherosclerosis, ischemia/reperfusion injury, hypertension, heart failure, diabetic cardiomyopathy, and drug-induced myocardial damage...

Endothelial dysfunction represents a major cardiovascular risk factor for hypertension. Sp1 and Sp3 belong to the specificity protein and Krüppel-like transcription factor families. They are ubiquitously expressed and closely associated with cardiovascular development. We investigate the role of Sp1 and Sp3 in endothelial cells in vivo and evaluate whether captopril, an angiotensin-converting enzyme inhibitor (ACEI), targets Sp1/Sp3 to exert its effects. Inducible endothelial-specific Sp1/Sp3 knockout mice are generated to elucidate their role in endothelial cells...

BACKGROUND: Obesity is a multifactorial disease with epigenetic manifestations that increases the prevalence of associated comorbidities such as metabolic syndrome, cardiovascular dysfunction, and major depression disorder. Given the aforementioned, a search for new pharmacological alternatives for the treatment of this disease is necessary. The current study aimed to evaluate the effects of histone deacetylase-3 (HDAC3) inhibition caused by RGFP966 (a benzamide-type HDAC inhibitor selective for HDAC3) administration, in an animal model of obesity induced by high-fat diet (HFD)...

Histone deacetylase 3 (HDAC3) and nuclear receptor co-repressor (NCoR1/2) are epigenetic regulators that play a key role in gene expression and metabolism. HDAC3 is a class I histone deacetylase that functions as a transcriptional co-repressor, modulating gene expression by removing acetyl groups from histones and non-histone proteins. NCoR1, on the other hand, is a transcriptional co-repressor that interacts with nuclear hormone receptors, including peroxisome proliferator-activated receptor gamma (PPARγ) and liver X receptor (LXR), to regulate metabolic gene expression...

As a significant non-communicable disease, cardiovascular disease is the leading cause of death for both men and women, comprises almost twenty percent of deaths in most racial and ethnic groups, can affect greater than twenty-five million individuals worldwide over the age of twenty, and impacts global economies with far-reaching financial challenges. Multiple factors can affect the onset of cardiovascular disease that include high serum cholesterol levels, elevated blood pressure, tobacco consumption and secondhand smoke exposure, poor nutrition, physical inactivity, obesity, and concurrent diabetes mellitus...

Maternal exercise during pregnancy has emerged as a potentially promising approach to protect offspring from cardiovascular disease, including hypertension. Although endothelial dysfunction is involved in the pathophysiology of hypertension, limited studies have characterized how maternal exercise influences endothelial function of hypertensive offspring. In this study, pregnant spontaneously hypertensive rats and Wistar-Kyoto rats were assigned either to a sedentary lifestyle or to swimming training daily, and fetal histone deacetylase-mediated epigenetic modification and offspring vascular function of mesenteric arteries were analyzed...

Cardiovascular diseases are severe diseases posing threat to human health because of their high morbidity and mortality worldwide. The incidence of diabetes mellitus is also increasing rapidly. Various signaling molecules are involved in the pathogenesis of cardiovascular diseases and diabetes. Sirtuin 6 (Sirt6), which is a class III histone deacetylase, has attracted numerous attentions since its discovery. Sirt6 enjoys a unique structure, important biological functions, and is involved in multiple cellular processes such as stress response, mitochondrial biogenesis, transcription, insulin resistance, inflammatory response, chromatin silencing, and apoptosis...

BACKGROUND: Progressive cardiac fibrosis leads to ventricular wall stiffness, cardiac dysfunction, and eventually heart failure, but the underlying mechanism remains unexplored. PDCD5 (programmed cell death 5) ubiquitously expresses in tissues, including the heart; however, the role of PDCD5 in cardiac fibrosis is largely unknown. Therefore, this study aims at exploring the possible role and underlying mechanisms of PDCD5 in the pathogenesis of cardiac fibrosis. METHODS AND RESULTS: PDCD5 levels were found to be elevated in the serum obtained from patients with cardiac fibrosis, in fibrotic mice heart tissues after myocardial infarction, and in cardiac fibroblasts stimulated by Ang II (angiotensin II)- or TGF-β1 (transforming growth factor-β1)...

Atherosclerosis (AS) is a chronic metabolic disorder and primary cause of cardiovascular diseases, resulting in substantial morbidity and mortality worldwide. Initiated by endothelial cell stimulation, AS is characterized by arterial inflammation, lipid deposition, foam cell formation, and plaque development. Nutrients such as carotenoids, polyphenols, and vitamins can prevent the atherosclerotic process by modulating inflammation and metabolic disorders through the regulation of gene acetylation states mediated with histone deacetylases (HDACs)...

Sirtuins (SIRTs) are a nicotinic adenine dinucleotide (+) -dependent histone deacetylase that regulates critical signaling pathways in prokaryotes and eukaryotes. Studies have identified seven mammalian homologs of the yeast SIRT silencing message regulator 2, namely, SIRT1-SIRT7. Recent in vivo and in vitro studies have successfully demonstrated the involvement of SIRTs in key pathways for cell biological function in physiological and pathological processes of the cardiovascular system, including processes including cellular senescence, oxidative stress, apoptosis, DNA damage, and cellular metabolism...

Clinical use of doxorubicin (Dox), an anthracycline with potent anti-tumor effects, is limited because of its highly chemotherapy-induced cardiotoxicity (CIC). After myocardial infarction (MI), we have recently identified Yin Yang-1 (YY1) and histone deacetylase 4 (HDAC4) as two factors involved in the overexpression of the isoform soluble suppression of tumorigenicity 2 (sST2) protein, which acts as a decoy receptor blocking the favorable effects of IL-33. Therefore, high levels of sST2 are associated with increased fibrosis, remodeling, and worse cardiovascular outcomes...

Histone Deacetylases (HDACs) deacetylate lysine residues in histone and non-histone proteins. HDACs have been implicated in several diseases, including cancer, neurodegeneration, and cardiovascular disease. HDACs play an essential role in gene transcription, cell survival, growth, and proliferation, with histone hypoacetylation as one of the critical downstream signatures. HDAC inhibitors (HDACi) regulate gene expression epigenetically by restoring acetylation levels. Contrarily, only few HDACi have received FDA approval, and the majority are presently undergoing clinical trials to ascertain their effectiveness in the prevention and treatment of disease...

Abdominal aortic aneurysm (AAA) is a multifactorial cardiovascular disease with a high risk of death, and it occurs in the infrarenal aorta with vascular dilatation. High blood pressure acts on the aortic wall, resulting in rupture and causing life-threatening intra-abdominal hemorrhage. Vascular smooth muscle cell (VSMC) dysregulation and extracellular matrix (ECM) degradation, especially elastin breaks, contribute to structural changes in the aortic wall. The pathogenesis of AAA includes the occurrence of oxidative stress, inflammatory cell infiltration, elastic fiber fragmentation, VSMC apoptosis, and phenotypic transformation...

PURPOSE: The Lumi-Solve photo-angioplasty drug eluting balloon catheter (DEBc) may afford safety advantages over current DEBc. Lumi-Solve utilises the guidewire (GW) port and lumen to deliver fibre-optic UV365nm light to the angioplasty balloon which may be problematic. We explore and evaluate alternative Lumi-Solve design options to circumvent fibre-optic use of the GW port and lumen which may enhance efficacy and clinical utility. METHODS: Effects of guidewire shadowing (GWS) on visible and UV365nm light transmission were evaluated and modelled in-silico...

Background Myocardial infarction (MI) is a cardiovascular disease with high morbidity and mortality. PI16 (peptidase inhibitor 16), as a secreted protein, is highly expressed in heart diseases such as heart failure. However, the functional role of PI16 in MI is unknown. This study aimed to investigate the role of PI16 after MI and its underlying mechanisms. Methods and Results PI16 levels after MI were measured by enzyme-linked immunosorbent assay and immunofluorescence staining, which showed that PI16 was upregulated in the plasma of patients with acute MI and in the infarct zone of murine hearts...

BACKGROUND: A large portion of idiopathic and familial dilated cardiomyopathy (DCM) cases have no obvious causal genetic variant. Although altered response to metabolic stress has been implicated, the molecular mechanisms underlying the pathogenesis of DCM remain elusive. The JMJD family proteins, initially identified as histone deacetylases, have been shown to be involved in many cardiovascular diseases. Despite their increasingly diverse functions, whether JMJD family members play a role in DCM remains unclear...

Aim: To investigate the clinical value of HDAC4 in coronary heart disease (CHD) patients. Methods: The serum HDAC4 levels were determined by ELISA in 180 CHD patients and 50 healthy controls. Results: HDAC4 was decreased in CHD patients compared with healthy controls (p < 0.001). HDAC4 was negatively linked with serum creatinine (p = 0.014), low-density lipoprotein cholesterol (p = 0.027) and C-reactive protein (p = 0.006) in CHD patients. Moreover, HDAC4 was inversely related to TNF-α (p = 0...

BACKGROUND: Aortic aneurysm and aortic dissection (AAD) are life-threatening vascular diseases, with endothelium being the primary target for AAD treatment. Protein S-sulfhydration is a newly discovered posttranslational modification whose role in AAD has not yet been defined. This study aims to investigate whether protein S-sulfhydration in the endothelium regulates AAD and its underlying mechanism. METHODS: Protein S-sulfhydration in endothelial cells (ECs) during AAD was detected and hub genes regulating homeostasis of the endothelium were identified...