Search results for "Up-Regulation"
showing 10 items of 455 documents
Epigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in mice.
2014
“Epigenetherapy” alters epigenetic status of the targeted chromatin and modifies expression of the endogenous therapeutic gene. In this study we used lentiviral in vivo delivery of small hairpin RNA (shRNA) into hearts in a murine infarction model. shRNA complementary to the promoter of vascular endothelial growth factor (VEGF-A) was able to upregulate endogenous VEGF-A expression. Histological and multiphoton microscope analysis confirmed the therapeutic effect in the transduced hearts. Magnetic resonance imaging (MRI) showed in vivo that the infarct size was significantly reduced in the treatment group 14 days after the epigenetherapy. Importantly, we show that promoter-targeted shRNA upr…
Atrial fibrillation is associated with cardiac hypoxia.
2008
BACKGROUND: Atrial fibrillation (AF), the most common human arrhythmia, is responsible for substantial morbidity and mortality and may be promoted by selective atrial ischemia and atrial fibrosis. Consequently, we investigated markers for hypoxia and angiogenesis in AF. METHODS: Right atrial appendages (n=158) were grouped according to heart rhythm [sinus rhythm (SR) or AF]. The degree of fibrosis and microvessel density of all patients were determined morphometrically using Sirius-Red- and CD34/CD105-stained sections, respectively. Next, sections (n=77) underwent immunostaining to detect hypoxia- and angiogenesis-related proteins [hypoxia-inducible factor (HIF)1 alpha, HIF2 alpha, vascular…
Farnesoid X receptor activation increases cholesteryl ester transfer protein expression in humans and transgenic mice
2013
International audience; Cholesteryl ester transfer protein (CETP) activity results in a proatherogenic lipoprotein profile. In cholestatic conditions, farnesoid X receptor (FXR) signaling by bile acids (BA) is activated and plasma HDL cholesterol (HDL-C) levels are low. This study tested the hypothesis that FXR-mediated induction of CETP contributes to this phenotype. Patients with cholestasis and high plasma BA had lower HDL-C levels and higher plasma CETP activity and mass compared with matched controls with low plasma BA (each P < 0.01). BA feeding in APOE3*Leiden transgenic mice expressing the human CETP transgene controlled by its endogenous promoter increased cholesterol within apoB-c…
Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted
2006
Abstract Tumours ferment glucose to lactate even in the presence of oxygen (aerobic glycolysis; Warburg effect). The pentose phosphate pathway (PPP) allows glucose conversion to ribose for nucleic acid synthesis and glucose degradation to lactate. The nonoxidative part of the PPP is controlled by transketolase enzyme reactions. We have detected upregulation of a mutated transketolase transcript (TKTL1) in human malignancies, whereas transketolase (TKT) and transketolase-like-2 (TKTL2) transcripts were not upregulated. Strong TKTL1 protein expression was correlated to invasive colon and urothelial tumours and to poor patients outcome. TKTL1 encodes a transketolase with unusual enzymatic prop…
2p15-p16.1 microdeletions encompassing and proximal to BCL11A are associated with elevated HbF in addition to neurologic impairment.
2015
Elevated fetal hemoglobin (HbF) ameliorates the clinical severity of hemoglobinopathies such as β-thalassemia and sickle cell anemia. Currently, the only curative approach for individuals under chronic transfusion/chelation support therapy is allogeneic stem cell transplantation. However, recent analyses of heritable variations in HbF levels have provided a new therapeutic target for HbF reactivation: the transcriptional repressor BCL11A. Erythroid-specific BCL11A abrogation is now actively being sought as a therapeutic avenue, but the specific impact of such disruption in humans remains to be determined. Although single nucleotide polymorphisms in BCL11A erythroid regulatory elements have …
Simultaneous determination in situ of DNA fragmentation and 8-oxoguanine in human sperm.
2009
Deoxyribonucleic acid fragmentation and oxidative DNA damage were simultaneously determined in the same sperm cell, incubating with an 8-oxoguanine DNA probe on human spermatozoa processed by the sperm chromatin dispersion test. The assay was validated by incubation with agents that induce DNA fragmentation with or without oxidative base damage. In all samples examined, increased levels of 8-oxoguanine were present only in those spermatozoa with fragmented DNA, suggesting a link between both DNA damage types.
Gastric relaxation induced by glucagon-like peptide-2 in mice fed a high-fat diet or fasted.
2011
Glucagon-like peptide-2 (GLP-2) is a nutrient-responsive gut hormone that increases the intestinal absorption. Exogenous GLP-2 also induces gastric fundus relaxation with possible implications for emptying rate or feeling of satiety. GLP-2 actions are mediated by GLP-2 receptor (GLP-2R), located on enteric neurons and myofibroblasts in murine gastrointestinal tract. Because it is not known whether changes in the endogenous GLP-2R levels occur in different nutritional states, we examined the GLP-2R gene and protein expression in gastric fundus from standard diet (STD)-fed, 12-h and 24-h fasted and re-fed, or high-fat diet (HFD)-fed mice and we analyzed the mechanical responses to exogenous G…
Endurance Exercise and Conjugated Linoleic Acid (CLA) Supplementation Up-Regulate CYP17A1 and Stimulate Testosterone Biosynthesis
2013
A new role for fat supplements, in particular conjugated linoleic acid (CLA), has been delineated in steroidogenesis, although the underlying molecular mechanisms have not yet been elucidated. The aims of the present study were to identify the pathway stimulated by CLA supplementation using a cell culture model and to determine whether this same pathway is also stimulated in vivo by CLA supplementation associated with exercise. In vitro, Leydig tumour rat cells (R2C) supplemented with different concentrations of CLA exhibited increasing testosterone biosynthesis accompanied by increasing levels of CYP17A1 mRNA and protein. In vivo, trained mice showed an increase in free plasma testosterone…
In vivo consequences of cholesterol-24S-hydroxylase (CYP46A1) inhibition by voriconazole on cholesterol homeostasis and function in the rat retina
2014
International audience; Cholesterol 24S-hydroxylase (CYP46A1) converts cholesterol into 24S-hydroxycholesterol in neurons and participates in cholesterol homeostasis in the central nervous system, including the retina. We aimed to evaluate the consequences of CYP46A1 inhibition by voriconazole on cholesterol homeostasis and function in the retina. Rats received daily intraperitoneal injections of voriconazole (60 mg/kg), minocycline (22 mg/kg), voriconazole plus minocycline, or vehicle during five consecutive days. The rats were submitted to electroretinography to monitor retinal functionality. Cholesterol and 24S-hydroxycholesterol were measured in plasma, brain and retina by gas chromatog…
Prognostic role of aldosterone in patients with acute coronary syndrome: short and medium term follow-up.
2013
AIMS: Different studies have shown a correlation between aldosterone, atherosclerosis and ischemia in the past decade. Evidence exists for the relationship between high levels of aldosterone and augmented risk of cardiovascular diseases, such as hypertension, cardiac failure, coronary artery disease and stroke. The objective of this study was to determine the prognostic role of aldosterone in patients with myocardial infarction. METHODS: The study population included 96 consecutive patients admitted to our department for ST-elevated and non-ST-elevated myocardial infarction from June 2009 to March 2012. Plasma aldosterone levels were measured at admission to hospital in all patients. A 2-ye…