MiRNAGE-34 induces cardiac damAGE.
Ontology highlight
ABSTRACT:
SUBMITTER: Emanueli C
PROVIDER: S-EPMC3698632 | biostudies-other | 2013 Jul
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Background It is known that dietary intake of polyunsaturated fatty acids may improve cardiac function. However, relatively high daily doses are required to achieve sufficient cardiac concentrations of beneficial omega-3 fatty acids. The liver X receptor (LXR) is a nuclear hormone receptor and a crucial regulator of lipid homeostasis in mammals. LXR activation has been shown to endogenously reprogram cellular lipid profiles toward increased polyunsaturated fatty acids levels. Here we studied whether LXR lipid reprogramming occurs in cardiac tissue and exerts cardioprotective actions. Methods and Results Male 129SV mice were treated with the LXR agonist AZ876 (20 µmol/kg per day) for 11 days. From day 6, the mice were injected with the nonselective β-agonist isoproterenol for 4 consecutive days to induce diastolic dysfunction and subendocardial fibrosis while maintaining systolic function. Treatment with isoproterenol led to a marked impairment of global longitudinal strain and the E/e' ratio of transmitral flow to mitral annular velocity, which were both significantly improved by the LXR agonist. Histological examination showed a significant reduction in isoproterenol-induced subendocardial fibrosis by AZ876. Analysis of the cardiac lipid composition by liquid chromatography-high resolution mass spectrometry revealed a significant increase in cardiac polyunsaturated fatty acids levels and a significant reduction in saturated fatty acids by AZ876. Conclusions The present study provides evidence that the LXR agonist AZ876 prevents subendocardial damage, improves global longitudinal strain and E/e' in a mouse model of isoproterenol-induced cardiac damage, accompanied by an upregulation of cardiac polyunsaturated fatty acids levels. Cardiac LXR activation and beneficial endogenous cardiac lipid reprogramming may provide a new therapeutic strategy in cardiac disease with diastolic dysfunction.
| S-EPMC8483473 | biostudies-literature
Project description:Acute kidney injury is associated with increased risk of heart failure and mortality. This study demonstrates that acute kidney injury induces remote cardiac dysfunction, damage, injury, and fibrosis via a galectin-3 (Gal-3) dependent pathway. Gal-3 originates from bone marrow-derived immune cells. Cardiac damage could be prevented by blocking this pathway.
| S-EPMC6834958 | biostudies-literature
Project description:BackgroundRenovascular hypertension (RVH) often manifest with metabolic syndrome (MetS) as well. Coexisting MetS and hypertension increases cardiovascular morbidity and mortality, but the mechanisms underlying cardiac injury remain unknown. We hypothesized that superimposition of MetS induces myocardial mitochondrial damage, leading to cardiac injury and dysfunction in swine RVH.MethodsPigs were studied after 16 weeks of diet-induced MetS with or without RVH (unilateral renal artery stenosis), and Lean controls (n = 6 each). Systolic and diastolic cardiac function were assessed by multidetector CT, and cardiac mitochondrial morphology (electron microscopy) and myocardial function in tissue and isolated mitochondria.ResultsBody weight was similarly higher in MetS groups vs. Lean. RVH groups achieved significant stenosis and developed hypertension. Mitochondrial matrix density and adenosine triphosphate production were lower and H2O2 production higher in RVH groups vs. Lean and MetS. Lean + RVH (but not MetS + RVH) activated mitophagy, which was associated with decreased myocardial expression of mitophagy-related microRNAs. MetS groups exhibited higher numbers of intermitochondrial junctions, which could have prevented membrane depolarization/activation of mitophagy in MetS + RVH. Cardiac fibrosis, hypertrophy (increased left ventricular muscle mass), and diastolic function (decreased E/A ratio) were greater in MetS + RVH vs. Lean + RVH.ConclusionsMetS+RVH induces myocardial mitochondrial damage and dysfunction. MetS + RVH failed to activate mitophagy, resulting in greater cardiac remodeling, fibrosis, and diastolic dysfunction. Mitochondrial injury and impaired mitophagy may constitute important mechanisms and therapeutic targets to ameliorate cardiac damage and dysfunction in patients with coexisting MetS and RVH.
| S-EPMC7951049 | biostudies-literature
Project description:Phytocannabinoids, with their variety of beneficial effects, represent a valid group of substances that could be employed as neurogenesis-enhancers or neuronal differentiation inducers. We focused our attention on the neuronal-related potential of cannabichromene (CBC) when administered to undifferentiated NSC-34 for 24 h. Transcriptomic analysis showed an upregulation of several neuronal markers, such as Neurod1 and Tubb3, as well as indicators of neuronal differentiation process progression, such as Pax6. An in-depth investigation of the processes involved in neuronal differentiation indicates positive cytoskeleton remodeling by upregulation of Cfl2 and Tubg1, and active differentiation-targeted transcriptional program, suggested by Phox2b and Hes1. After 48 h of treatment, the markers previously examined in the transcriptomic analysis are still overexpressed, like Ache and Hes1, indicating that the differentiation process is still in progress. The lack of GFAP protein suggests that no astroglial differentiation is taking place, and it is reasonable to indicate the neuronal one as the ongoing one. These results indicate CBC as a potential neuronal differentiation inducer for NSC-34 cells.
| S-EPMC10051538 | biostudies-literature
Project description:MicroRNA (miRNA) expression is tightly regulated by several mechanisms, including transcription and cleavage of the miRNA precursor RNAs, to generate a mature miRNA, which is thought to be directly correlated with activity. MiR-34 is a tumour-suppressor miRNA important in cell survival, that is transcriptionally upregulated by p53 in response to DNA damage. Here, we show for the first time that there is a pool of mature miR-34 in cells that lacks a 5'-phosphate and is inactive. Following exposure to a DNA-damaging stimulus, the inactive pool of miR-34 is rapidly activated through 5'-end phosphorylation in an ATM- and Clp1-dependent manner, enabling loading into Ago2. Importantly, this mechanism of miR-34 activation occurs faster than, and independently of, de novo p53-mediated transcription and processing. Our study reveals a novel mechanism of rapid miRNA activation in response to environmental stimuli occurring at the mature miRNA level.
| S-EPMC4802117 | biostudies-literature
Project description:Previous studies have shown that lncRNA small nuclear RNA host gene 7 (lncRNA SNHG7) played an important role in cancer progression. However, the role of lncRNA SNHG7 in cardiac fibrosis is still poorly understood. In this study, the results of quantitative real time polymerase chain reaction (qRT-PCR) analysis showed that lncRNA SNHG7 was over expressed in the infarcted and peri-infarcted area in the left ventricle after MI in mice. Western blot analysis showed that knockdown of SNHG7 decreased the expression of collagen type 1 (Col1)and ?-smooth muscle actin (?-SMA). Echocardiographic study suggested that inhibition of SNHG7 improved cardiac function after MI in mice. Luciferase assay indicated SNHG7 could act as a competing endogenous RNA (ceRNA) by sponging miR-34-5p. The MTT cell proliferation assay and 5-ethynyl-2'-deoxyuridine (EdU) labelling assay revealed that co-transfection of SNHG7 and miR-34-5p inhibited cell viability and proliferation of cardiac fibroblasts (CF). All the results indicated that lncRNA SNHG7 could promote cardiac fibrosis via targeting miR-34-5p through acting as a ceRNA in mice after MI. Silencing of SNHG7 could attenuate deposition of collagens and improve cardiac function. miR-34-5p could suppress the fibrogenesis of CF by targeting ROCK1 and abolish SNHG7-induced CF proliferation and fibroblast-to-myofibroblast transition.
| S-EPMC7346013 | biostudies-literature
Project description:Prospective imaging with electrocardiogram (ECG) and respiratory gating presents an imaging application that leverages the improved image quality of high-frequency (>20 MHz) annular arrays without the need for rapid mechanical motion. The limitation of prospective imaging is that the object being imaged must have a periodically stable motion. The present study investigated the implementation of prospective imaging with a 34 MHz annular-array scan system to image the mouse heart at high effective frame rates, >200 frames/s (fps). M-mode data for all transmit-to-receive pairs were acquired at a series of spatial locations using ECG and respiratory gating, and the data were then synthetically focused in postprocessing. The pulse-repetition frequency of the M-mode data determined the effective frame rate of the final B-mode image sequence. The hearts of adult mice were prospectively imaged and compared with retrospective data acquired with a commercial ultrasonic biomicroscope (UBM). The annular array data were acquired at an effective frame rate of 500 fps spanning 0.5 s, and the UBM data were acquired at 1000 fps spanning 0.15 s. The resulting images showed that multiple heart cycles could be clearly resolved using prospective imaging and that synthetic focusing improved image resolution and SNR of the right ventricle, interventricular septum, posterior edge of the left ventricle (LV), and papillary muscles of the LV versus fixed-focused imaging and the retrospective imaging of the UBM machine.
| S-EPMC2752351 | biostudies-literature
Project description:This study reveals a new complexity in the cellular response to DNA damage: activation of IFN signaling. The DNA damage response involves the rapid recruitment of repair enzymes and the activation of signal transducers that regulate cell-cycle checkpoints and cell survival. To understand the link between DNA damage and the innate cellular defense that occurs in response to many viral infections, we evaluated the effects of agents such as etoposide that promote dsDNA breaks. Treatment of human cells with etoposide led to the induction of IFN-stimulated genes and the IFN-? and IFN-? genes. NF-?B, known to be activated in response to DNA damage, was shown to be a key regulator of this IFN gene induction. Expression of an NF-?B subunit, p65/RelA, was sufficient for induction of the human IFN-?1 gene. In addition, NF-?B was required for the induction of IFN regulatory factor-1 and -7 that are able to stimulate expression of the IFN-? and IFN-? genes. Cells that lack the NF-?B essential modulator lack the ability to induce the IFN genes following DNA damage. Breaks in DNA are generated during normal physiological processes of replication, transcription, and recombination, as well as by external genotoxic agents or infectious agents. The significant finding of IFN production as a stress response to DNA damage provides a new perspective on the role of IFN signaling.
| S-EPMC3246365 | biostudies-literature
Project description:Heart failure is a leading cause of mortality in developed countries. Cell death is a key player in the development of heart failure. Calcium-independent phospholipase A2β (iPLA2β) produces lipid mediators by catalyzing lipids and induces nuclear shrinkage in caspase-independent cell death. Here, we show that lysophosphatidylserine generated by iPLA2β induces necrotic cardiomyocyte death, as well as contractile dysfunction mediated through its receptor, G protein-coupled receptor 34 (GPR34). Cardiomyocyte-specific iPLA2β-deficient male mice were subjected to pressure overload. While control mice showed left ventricular systolic dysfunction with necrotic cardiomyocyte death, iPLA2β-deficient mice preserved cardiac function. Lipidomic analysis revealed a reduction of 18:0 lysophosphatidylserine in iPLA2β-deficient hearts. Knockdown of Gpr34 attenuated 18:0 lysophosphatidylserine-induced necrosis in neonatal male rat cardiomyocytes, while the ablation of Gpr34 in male mice reduced the development of pressure overload-induced cardiac remodeling. Thus, the iPLA2β-lysophosphatidylserine-GPR34-necrosis signaling axis plays a detrimental role in the heart in response to pressure overload.
| S-EPMC10390482 | biostudies-literature
Project description:Centrosomal abnormalities are frequently observed in cancers and in cells with defective DNA repair. Here, we used light and electron microscopy to show that DNA damage induces centrosome amplification, not fragmentation, in human cells. Caffeine abrogated this amplification in both ATM (ataxia telangiectasia, mutated)- and ATR (ATM and Rad3-related)-defective cells, indicating a complementary role for these DNA-damage-responsive kinases in promoting centrosome amplification. Inhibition of checkpoint kinase 1 (Chk1) by RNA-mediated interference or drug treatment suppressed DNA-damage-induced centrosome amplification. Radiation-induced centrosome amplification was abrogated in Chk1(-/-) DT40 cells, but occurred at normal levels in Chk1(-/-) cells transgenically expressing Chk1. Expression of kinase-dead Chk1, or Chk1S345A, through which the phosphatidylinositol-3-kinase cannot signal, failed to restore centrosome amplification, showing that signalling to Chk1 and Chk1 catalytic activity are necessary to promote centrosome overduplication after DNA damage.
| S-EPMC2002539 | biostudies-literature