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Chronic isoprenaline/phenylephrine vs. exclusive isoprenaline stimulation in mice: critical contribution of alpha1-adrenoceptors to early cardiac stress responses

ABSTRACT: Chronic isoprenaline/phenylephrine vs. exclusive isoprenaline stimulation in mice: critical contribution of alpha1-adrenoceptors to early cardiac stress responses

PROVIDER: PRJNA800748 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17762340.fastq.gz	Fastqsanger.gz
	SRR17762341.fastq.gz	Fastqsanger.gz
	SRR17762342.fastq.gz	Fastqsanger.gz
	SRR17762343.fastq.gz	Fastqsanger.gz
	SRR17762344.fastq.gz	Fastqsanger.gz

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Chronic isoprenaline/phenylephrine vs. exclusive isoprenaline stimulation in mice: critical contribution of alpha1-adrenoceptors to early cardiac stress responses

Project description:Mice were subjected to either isoprenaline (ISO, 30 mg/kg*d) or isoprenaline and phenylephrine (ISO/PE, 30 mg/kg*d each) for a period of 4 days via osmotic minipumps. At that timepoint, both ISO and ISO/PE treated animals showed a similar increase in heart weight to tibia length ratios. ECG-telemetry data collected from other individuals indicate a similar increase heart rate and normal blood pressure after 4 days of both ISO and ISO/PE exposure. Cardiac function was not assessed at that particular timepoint.

2022-02-23 | GSE195466 | GEO

Chronic isoprenaline/phenylephrine vs. exclusive isoprenaline stimulation in mice: critical contribution of alpha<sub>1</sub>-adrenoceptors to early cardiac stress responses.

Project description:Hyperactivity of the sympathetic nervous system is a major driver of cardiac remodeling, exerting its effects through both α-, and β-adrenoceptors (α-, β-ARs). As the relative contribution of subtype α1-AR to cardiac stress responses remains poorly investigated, we subjected mice to either subcutaneous perfusion with the β-AR agonist isoprenaline (ISO, 30 mg/kg × day) or to a combination of ISO and the stable α1-AR agonist phenylephrine (ISO/PE, 30 mg/kg × day each). Telemetry analysis revealed similar hemodynamic responses under both ISO and ISO/PE treatment i.e., permanently increased heart rates and only transient decreases in mean blood pressure during the first 24 h. Echocardiography and single cell analysis after 1 week of exposure showed that ISO/PE-, but not ISO-treated animals established α1-AR-mediated inotropic responsiveness to acute adrenergic stimulation. Morphologically, additional PE perfusion limited concentric cardiomyocyte growth and enhanced cardiac collagen deposition during 7 days of treatment. Time-course analysis demonstrated a diverging development in transcriptional patterns at day 4 of treatment i.e., increased expression of selected marker genes Xirp2, Nppa, Tgfb1, Col1a1, Postn under chronic ISO/PE treatment which was either less pronounced or absent in the ISO group. Transcriptome analyses at day 4 via RNA sequencing demonstrated that additional PE treatment caused a marked upregulation of genes allocated to extracellular matrix and fiber organization along with a more pronounced downregulation of genes involved in metabolic processes, muscle adaptation and cardiac electrophysiology. Consistently, transcriptome changes under ISO/PE challenge more effectively recapitulated early transcriptional alterations in pressure overload-induced experimental heart failure and in human hypertrophic cardiomyopathy.

| S-EPMC8921177 | biostudies-literature

Gene expression profiling of human-derived primary cardiomyocytes with lncRNA ZNF593-AS 5‘ end overexpression under phenylephrine stimulation

Project description:The aim of this study is to investigate molecular mechanisms underlying the function of lncRNA ZNF593-AS in cardiomyocyte under phenylephrine stimulation in vitro.

2020-12-22 | GSE163645 | GEO

A Comparison of Neonatal Rat Ventricular Myocytes Treated With Phenylephrine or PAMH

Project description:Neonatal rat ventricular myocytes cultured for 48 hours without stimulation, in the presence of twenty micromolar phenylephrine, or in the presence of one micromolar PAMH. Keywords = Rattus Keywords = Ventricular Myocytes Keywords = Cardiomyocytes Keywords = Hypertrophy Keywords = Phenylephrine Keywords = PAMH Keywords = 5-hydroxytryptamine Keywords = Pyridine Keywords: repeat sample

2004-03-02 | GSE925 | GEO

Expression data from mice bladder with MB49-induced cancer treated with alpha1-oleate.

Project description:Potent chemotherapeutic agents are required to counteract the aggressive behavior of cancer cells and patients often experience severe side effects, due to tissue toxicity. This study addresses if a better balance between efficacy and toxicity can be attained using the tumoricidal complex alpha1-oleate, formed by a synthetic, alpha-helical peptide comprising the N-terminal 39 amino acids of alpha-lactalbumin and the fatty acid oleic acid. Bladder cancer was established, by intra-vesical instillation of MB49 cells on day 0 and the treatment group received five instillations of alpha1-oleate (1.7-17mM) on days 3-11. A dose-dependent reduction in tumor size, bladder size and bladder weight was recorded in the alpha1-oleate treated group, compared to sham-treated mice. Tumor markers Ki-67, Cyclin D1 and VEGF were inhibited in a dose-dependent manner, as was the expression of cancer-related genes. Remarkably, toxicity for healthy tissue was not detected in alpha1-oleate-treated, tumor bearing mice or in healthy mice or rabbits, challenged with increasing doses of the active complex. The results define a dose-dependent therapeutic effect of alpha1-oleate in a murine bladder cancer model.

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LncRNA Chaer contributes to the transcriptome reprogramming during phenylephrine-induced hypertrophy in neonatal rat ventricular myocytes

Project description:We compared the transcriptome modified by siRNA-mediated cardiac hypertrophy associated epigenentic regulator (Chaer) with negative control siRNA treated neonatal rat ventricular myocytes with or without phenylephrine treatment. The results suggest that Chaer knockdown broadly blocks the phenylephrine-induced hypertrophic programming of the transcriptome. Transcripts profiles from neonatal rat ventricular myocytes with or without phenylephrine and with or without Chaer-specific siRNA compared to negative control siRNA

2016-06-30 | E-GEOD-82339 | biostudies-arrayexpress

LncRNA Chaer contributes to the transcriptome reprogramming during phenylephrine-induced hypertrophy in neonatal rat ventricular myocytes

2016-06-30 | GSE82339 | GEO

Expression data from mice bladder with MB49-induced cancer treated with alpha1-oleate alone or in combination Epirubicin or Mitomycin C, short-term effects

Project description:Bladder cancer is common and one of the most costly cancer forms, due to a lack of curative therapies. Recently, clinical safety and efficacy of the alpha1-oleate complex was demonstrated in a placebo-controlled study of non-muscle invasive bladder cancer. This study investigated if long-term therapeutic efficacy is improved by repeated treatment cycles and by combining alpha1-oleate with low-dose chemotherapy. Rapidly growing bladder tumors were treated by intravesical instillation of alpha1-oleate, Epirubicin or Mitomycin C alone or in combination. One treatment cycle arrested tumor growth, with a protective effect lasting at least four weeks in mice receiving 8.5 mM of alpha1-oleate alone or 1.7 mM of alpha-oleate combined with Epirubicin or Mitomycin C. Repeated treatment cycles extended protection, defined by a lack of bladder pathology and a virtual absence of bladder cancer-specific gene expression. Synergy with Epirubicin was detected at the lower alpha1-oleate concentration and alpha1-oleate was shown to enhance the uptake and nuclear translocation of Epirubicin, by tumor cells. Effects at the chromatin level affecting cell proliferation were further suggested by reduced BrdU incorporation. In addition, alpha1-oleate triggered DNA fragmentation, defined by the TUNEL assay. The results suggest that bladder cancer development may be prevented long-term in the murine model, by alpha1-oleate alone or in combination with low-dose Epirubicin. In addition, the combination of alpha1-oleate and Epirubicin reduced the size of established tumors. Exploring these potent preventive and therapeutic effects will be of immediate interest in patients with bladder cancer.

2023-02-25 | GSE209882 | GEO

Expression data from mice bladder with MB49-induced cancer treated with alpha1-oleate alone or in combination Epirubicin or Mitomycin C, long-term effects

2023-02-25 | GSE209881 | GEO

Mice inflammatory responses to inhaled aerosolized LPS: effects of various forms of human alpha1-antitrypsin

Project description:Characterize how Balb/c mice responses to aerosolized LPS (lipopolysaccharide) alone or with intraperitoneal (i.p.) delivery of alpha1-antitrypsin (AAT)

2022-09-30 | GSE214249 | GEO

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