Development of a novel murine heart failure model overexpressing human renin and angiotensinogen.


:Renin is the rate-limiting enzyme of the renin-angiotensin system cascade, which drives the pathophysiological progression of heart failure. Species differences in the amino acid sequence of the catalytic domain of renin limit evaluations of the potency and efficacy of human renin inhibitors in animal models, and a high dose of inhibitors is usually needed to show its organ-protective effects in rodents. In the present study, we developed a novel murine heart failure model (triple-tg) to enable us to evaluate the cardioprotective effect of renin inhibitors at more relevant doses for humans, by cross-breeding calsequestrin transgenic (CSQ-tg) mice with human renin and human angiotensinogen double-transgenic mice. The triple-tg mice exhibited increased plasma renin activity, worsened cardiac hypertrophy, and higher mortality compared to CSQ-tg mice. Triple-tg mice treated with 10 mg·kg-1 of TAK-272 (imarikiren/SCO-272), an orally active direct renin inhibitor, exhibited improvements in heart failure phenotypes, such as cardiac hypertrophy and survival rate; however, a dose of 300 mg·kg-1 was required to improve symptoms in CSQ-tg mice. Our results suggest that this newly generated triple-tg heart failure model is useful to evaluate the cardioprotective effects of human renin inhibitors at clinically relevant doses, thereby minimizing the concerns of off-target effects related to much higher drug exposure than that achieved in clinical study.


FEBS Open Bio


FEBS open bio


Hara T,Yamamura T,Murakami-Asahina M,Matsumoto H,Takeyama M,Kanagawa R,Nishimoto T




Has Abstract


2020-05-01 00:00:00










  • Structure of the C-terminal domain of AspA (antigen I/II-family) protein from Streptococcus pyogenes.

    abstract::The pathogenic bacteria Streptococcus pyogenes can cause an array of diseases in humans, including moderate infections such as pharyngitis (strep throat) as well as life threatening conditions such as necrotizing fasciitis and puerperal fever. The antigen I/II family proteins are cell wall anchored adhesin proteins fo...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Hall M,Nylander S,Jenkinson HF,Persson K

    更新日期:2014-03-12 00:00:00

  • Comparison of a new nanoform of the photosensitizer chlorin e6, based on plant phospholipids, with its free form.

    abstract::Photodynamic therapy is an advanced method of treating cancer and various benign diseases, including infections. It uses light-activated molecules [photosensitizers (PSs)] to generate reactive oxygen species (ROS) when irradiated with light of a specific wavelength. This study examined the photophysical and photosensi...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Kostryukova LV,Prozorovskiy VN,Medvedeva NV,Ipatova OM

    更新日期:2018-01-02 00:00:00

  • Eukaryotic translation initiation factor 3 subunit D overexpression is associated with the occurrence and development of ovarian cancer.

    abstract::Ovarian cancer is the most common cause of gynaecological cancer-associated death; thus, promising biomarkers and new therapeutic targets for ovarian cancer must be explored. Here, we report that eukaryotic translation initiation factor 3 subunit D (EIF3D), a member of the EIF3 family, was overexpressed in ovarian can...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Lin Y,Zhang R,Zhang P

    更新日期:2016-10-31 00:00:00

  • Tropomyosin isoforms have specific effects on the transcriptome of undifferentiated and differentiated B35 neuroblastoma cells.

    abstract::Tropomyosins, a family of actin-associated proteins, bestow actin filaments with distinct biochemical and physical properties which are important for determining cell shape and regulating many cellular processes in eukaryotic cells. Here, we used RNA-seq to investigate the effect of four tropomyosin isoforms on gene e...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Stefen H,Suchowerska AK,Chen BJ,Brettle M,Kuschelewski J,Gunning PW,Janitz M,Fath T

    更新日期:2018-02-19 00:00:00

  • Quercetin-3-glucoside increases low-density lipoprotein receptor (LDLR) expression, attenuates proprotein convertase subtilisin/kexin 9 (PCSK9) secretion, and stimulates LDL uptake by Huh7 human hepatocytes in culture.

    abstract::Low-density lipoprotein receptor (LDLR) mediates hepatic clearance of plasma cholesterol; proprotein convertase subtilisin/kexin 9 (PCSK9) opposes this clearance by promoting LDLR degradation. The plant flavonoid quercetin-3-β-d-glucoside (Q3G) has been shown to reduce hypercholesterolemia in experimental animals. Her...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Mbikay M,Sirois F,Simoes S,Mayne J,Chrétien M

    更新日期:2014-09-02 00:00:00

  • A new protocol for long-term culture of a specific subpopulation of liver cancer stem cells enriched by cell surface markers.

    abstract::Liver cancer stem cells (L-CSCs) are considered to be an important therapeutic target for hepatocellular carcinoma (HCC). This study provides a new in vitro long-term culture model for a specific subpopulation of L-CSCs enriched by cell surface markers. We combined CD13, CD133 and EpCAM to selectively enrich L-CSCs, w...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Zhang B,Wang HY,Wang DX,Zeng Q,Fan Z,Xi JF,Nan X,He LJ,Zhou JN,Pei XT,Yue W

    更新日期:2020-09-01 00:00:00

  • Niclosamide and its derivative DK-520 inhibit RANKL-induced osteoclastogenesis.

    abstract::Niclosamide is a potent inhibitor of osteoclastogenesis and bone remodeling. DK-520 is an acyl derivative of Niclosamide and significantly increased both the plasma concentration and the duration of exposure of Niclosamide when dosed orally. However, at present the effect of DK-520 on osteoclastogenesis has not been r...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Jiao Y,Chen C,Hu X,Feng X,Shi Z,Cao J,Li Q,Zhu Y

    更新日期:2020-08-01 00:00:00

  • In vivo assay to monitor flavonoid uptake across plant cell membranes.

    abstract::Flavonoids represent one of the most important molecules of plant secondary metabolism, playing many different biochemical and physiological roles. Although their essential role in plant life and human health has been elucidated by many studies, their subcellular transport and accumulation in plant tissues remains unc...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Filippi A,Petrussa E,Peresson C,Bertolini A,Vianello A,Braidot E

    更新日期:2015-08-29 00:00:00

  • Lithium chloride ameliorates cognition dysfunction induced by sevoflurane anesthesia in rats.

    abstract::Postoperative cognitive dysfunction is a common complication in elderly patients after surgeries involving anesthesia, but the underlying mechanisms are poorly understood. Lithium is a conventional treatment for bipolar disorder, which exerts a neuroprotective role in various diseases by inhibiting glycogen synthase k...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Wang Y,An X,Zhang X,Liu J,Wang J,Yang Z

    更新日期:2019-12-22 00:00:00

  • Characterization of the cHS4 insulator in mouse embryonic stem cells.

    abstract::Synthetic biology circuits are often constructed with multiple gene expression units assembled in close proximity, and they can be used to perform complex functions in embryonic stem cells (ESCs). However, mutual interference between transcriptional units has not been well studied in mouse ESCs. To assess the efficien...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Lu XB,Guo YH,Huang W

    更新日期:2020-04-01 00:00:00

  • High-intensity focused ultrasound inhibits invasion and metastasis of colon cancer cells by enhancing microRNA-124-mediated suppression of STAT3.

    abstract::Metastasis is the primary contributor to colorectal cancer mortality. High-intensity focused ultrasound (HIFU) is an emerging technology for tumor therapy that exerts its effects through tumor ablation, mechanical disruption, and enhancement of immune responses. However, it remains unclear whether HIFU can influence t...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Li M,Wan G,Yu H,Xiong W

    更新日期:2019-06-01 00:00:00

  • Functional and structural characterization of HspB1/Hsp27 from Chinese hamster ovary cells.

    abstract::Small heat shock proteins (sHsps) endow cells with stress tolerance. Of the various sHsps in mammals, HspB1, also known as Hsp27, is the most ubiquitous. To examine the structure and function of HspB1, we expressed, purified, and characterized HspB1 from Chinese hamster (Cricetulus griseus) ovary cells (CgHspB1). CgHs...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Sha E,Nakamura M,Ankai K,Yamamoto YY,Oka T,Yohda M

    更新日期:2019-10-01 00:00:00

  • Interaction of Carthamus tinctorius lignan arctigenin with the binding site of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase.

    abstract::Mediterranean Carthamus tinctorius (Safflower) is used for treatment of inflammatory conditions and neuropsychiatric disorders. Recently C. tinctorius lignans arctigenin and trachelogenin but not matairesinol were described to interfere with the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO)...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Temml V,Kuehnl S,Schuster D,Schwaiger S,Stuppner H,Fuchs D

    更新日期:2013-09-07 00:00:00

  • Cryo-electron microscopy visualization of a large insertion in the 5S ribosomal RNA of the extremely halophilic archaeon Halococcus morrhuae.

    abstract::The extreme halophile Halococcus morrhuae (ATCC® 17082) contains a 108-nucleotide insertion in its 5S rRNA. Large rRNA expansions in Archaea are rare. This one almost doubles the length of the 5S rRNA. In order to understand how such an insertion is accommodated in the ribosome, we obtained a cryo-electron microscopy ...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Tirumalai MR,Kaelber JT,Park DR,Tran Q,Fox GE

    更新日期:2020-10-01 00:00:00

  • Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced inflammatory bone resorption, and protects against alveolar bone loss in mice.

    abstract::Epigallocatechin gallate (EGCG), a major polyphenol in green tea, possesses antioxidant properties and regulates various cell functions. Here, we examined the function of EGCG in inflammatory bone resorption. In calvarial organ cultures, lipopolysaccharide (LPS)-induced bone resorption was clearly suppressed by EGCG. ...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Tominari T,Matsumoto C,Watanabe K,Hirata M,Grundler FM,Miyaura C,Inada M

    更新日期:2015-06-12 00:00:00

  • p38α controls self-renewal and fate decision of neurosphere-forming cells in adult hippocampus.

    abstract::Neural stem cells (NSC) from the adult hippocampus easily lose their activity in vitro. Efficient in vitro expansion of adult hippocampus-derived NSC is important for generation of tools for research and cell therapy. Here, we show that a single copy disruption or pharmacological inhibition of p38α enables successful ...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Yoshioka K,Namiki K,Sudo T,Kasuya Y

    更新日期:2015-05-08 00:00:00

  • Seasonal variations in photoperiod affect hepatic metabolism of medaka (Oryzias latipes).

    abstract::Organisms living in temperate regions are sensitive to seasonal variations in the environment; they are known to accumulate energy as fat in their livers during the winter when days are shorter, temperatures are lower, and food is scarce. However, the effect of variations in photoperiod alone on hepatic lipid metaboli...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Fujisawa K,Takami T,Shintani H,Sasai N,Matsumoto T,Yamamoto N,Sakaida I

    更新日期:2021-01-21 00:00:00

  • Characterization of an intertidal zone metagenome oligoribonuclease and the role of the intermolecular disulfide bond for homodimer formation and nuclease activity.

    abstract::The gene encoding MG Orn has been identified from a metagenomic library created from the intertidal zone in Svalbard and encodes a protein of 184 amino acid residues. The mg orn gene has been cloned, recombinantly expressed in Escherichia coli, and purified to homogeneity. Biochemical characterization of the enzyme sh...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Piotrowski Y,Berg K,Klebl DP,Leiros I,Larsen AN

    更新日期:2019-10-01 00:00:00

  • Expression patterns of kiss2 and gpr54-2 in Monopterus albus suggest these genes may play a role in sex reversal in fish.

    abstract::Due to its exceptionally small genome size and protogynous hermaphroditism, Monopterus albus has been proposed as a model for vertebrate sexual development. The Kiss/GPR54 system is a central regulator of sexual development in most vertebrates, but its role in sex reversal remains hypothetical. In contrast to mammals,...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Yi TL,Pei MT,Yang DQ

    更新日期:2019-10-01 00:00:00

  • A new high-resolution crystal structure of the Drosophila melanogaster angiotensin converting enzyme homologue, AnCE.

    abstract::Angiotensin converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase with an essential role in blood pressure homeostasis in mammals. ACE has long been targeted in the treatment of hypertension through ACE inhibitors, however current inhibitors are known to cause severe side effects. Therefore, there is...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Harrison C,Acharya KR

    更新日期:2015-08-11 00:00:00

  • Hypoxia affects Slc7a5 expression through HIF-2α in differentiated neuronal cells.

    abstract::An imbalance of branched-chain amino acids (BCAAs) in the brain may result in neuropathological conditions, such as autism spectrum disorders. The L-type amino acid transporter 1 (LAT1), encoded by the solute carrier transporter 7a5 (Slc7a5) gene, is critical for maintaining normal levels of BCAAs in the brain. Howeve...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Onishi Y,Hiraiwa M,Kamada H,Iezaki T,Yamada T,Kaneda K,Hinoi E

    更新日期:2019-01-07 00:00:00

  • The levels of RAC3 expression are up regulated by TNF in the inflammatory response.

    abstract::RAC3 is a coactivator of glucocorticoid receptor and nuclear factor-κB (NF-κB) that is usually over-expressed in tumors and which also has important functions in the immune system. We investigated the role of the inflammatory response in the control of RAC3 expression levels in vivo and in vitro. We found that inflamm...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Alvarado CV,Rubio MF,Fernández Larrosa PN,Panelo LC,Azurmendi PJ,Ruiz Grecco M,Martínez-Nöel GA,Costas MA

    更新日期:2014-05-02 00:00:00

  • A novel assay for measuring recombinant human lysophosphatidylcholine acyltransferase 3 activity.

    abstract::Lysophosphatidylcholine acyltransferase 3 (LPCAT3) is an important enzyme in phospholipid remodeling, a process that influences the biophysical properties of cell membranes and thus cell function. Multiple lines of evidence suggest that LPCAT3 is involved in several diseases, including atherosclerosis, non-alcoholic s...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Du X,Hu J,Zhang Q,Liu Q,Xiang X,Dong J,Lou B,He S,Gu X,Cao Y,Li Y,Ding T

    更新日期:2019-10-01 00:00:00

  • An autophagy-related long non-coding RNA signature for glioma.

    abstract::Glioma is one of the most common types of malignant primary central nervous system tumor, and prognosis for this disease is poor. As autophagic drugs have been reported to induce glioma cell death, we investigated the potential prognostic role of autophagy-associated long non-coding RNA (lncRNA) in glioma patients. In...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Luan F,Chen W,Chen M,Yan J,Chen H,Yu H,Liu T,Mo L

    更新日期:2019-03-05 00:00:00

  • FGT-1-mediated glucose uptake is defective in insulin/IGF-like signaling mutants in Caenorhabditis elegans.

    abstract::Insulin signaling plays a central role in the regulation of facilitative glucose transporters (GLUTs) in humans. To establish Caenorhabditis elegans (C. elegans) as a model to study the mechanism underlying insulin regulation of GLUT, we identified that FGT-1 is most likely the only functional GLUT homolog in C. elega...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Kitaoka S,Morielli AD,Zhao FQ

    更新日期:2016-04-21 00:00:00

  • Fluoride resistance capacity in mammalian cells involves complex global gene expression changes.

    abstract::Fluorine is a bone-seeking element ubiquitously present in the environment and widely used in many oral hygiene products. In humans, excessive intake of fluoride may cause dental and skeletal fluorosis. However, endemic fluorosis does not appear to develop in a proportion of individuals exposed to the same levels of f...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Ran S,Sun N,Liu Y,Zhang W,Li Y,Wei L,Wang J,Liu B

    更新日期:2017-06-05 00:00:00

  • Cyclophilin D-dependent mitochondrial permeability transition amplifies inflammatory reprogramming in endotoxemia.

    abstract::Microorganisms or LPS (lipopolysaccharide), an outer membrane component of Gram-negative bacteria, can induce a systemic inflammatory response that leads to sepsis, multiple organ dysfunction, and mortality. Here, we investigated the role of cyclophilin D (CypD)-dependent mitochondrial permeability transition (mPT) in...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Veres B,Eros K,Antus C,Kalman N,Fonai F,Jakus PB,Boros E,Hegedus Z,Nagy I,Tretter L,Gallyas F Jr,Sumegi B

    更新日期:2021-01-20 00:00:00

  • Iron overload inhibits self-renewal of human pluripotent stem cells via DNA damage and generation of reactive oxygen species.

    abstract::Iron overload affects the cell cycle of various cell types, but the effect of iron overload on human pluripotent stem cells has not yet been reported. Here, we show that the proliferation capacities of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) were significantly inhibited by ...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Han Z,Xu Z,Chen L,Ye D,Yu Y,Zhang Y,Cao Y,Djibril B,Guo X,Gao X,Zhang W,Yu M,Liu S,Yan G,Jin M,Huang Q,Wang X,Hua B,Feng C,Yang F,Ma W,Liu Y

    更新日期:2020-05-01 00:00:00

  • Knockout of cytochrome P450 1A1 enhances lipopolysaccharide-induced acute lung injury in mice by targeting NF-κB activation.

    abstract::Acute lung injury (ALI) is accompanied by overactivation of multiple pro-inflammatory factors. Cytochrome P450 1A1 (CYP1A1) has been shown to aggravate lung injury in response to hyperoxia. However, the relationship between CYP1A1 and lipopolysaccharide (LPS)-induced ALI is unknown. In this study, CYP1A1 was shown to ...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Tian LX,Tang X,Ma W,Wang J,Zhang W,Liu K,Chen T,Zhu JY,Liang HP

    更新日期:2020-09-15 00:00:00

  • Identification and analysis of micro-exons in AP2/ERF and MADS gene families.

    abstract::Micro-exons are a set of ultrashort exons with lengths ≤ 51 nucleotides. Our previous study revealed that micro-exons were enriched in AP2 domains and K-box domains, which are crucial components of AP2/ERF (APETALA2/ethylene-responsive element-binding protein) and MADS-box (an acronym of MCM1, AGAMOUS, DEFICIENS and S...

    journal_title:FEBS open bio

    pub_type: 杂志文章


    authors: Song Q,Bari A,Li H,Chen LL

    更新日期:2020-12-01 00:00:00