scholarly journals Meox1 accelerates myocardial hypertrophic decompensation through Gata4

2017 ◽  
Vol 114 (2) ◽  
pp. 300-311 ◽  
Author(s):  
Dan Lu ◽  
Jizheng Wang ◽  
Jing Li ◽  
Feifei Guan ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Pressure Overload ◽  
Digital Gene Expression ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Mouse Heart ◽  
Activity Data ◽  
Aberrant Expression ◽  
Downstream Target ◽  
Pathological Hypertrophy ◽  
Entry Points

AbstractAimsPathological hypertrophy is the result of gene network regulation, which ultimately leads to adverse cardiac remodelling and heart failure (HF) and is accompanied by the reactivation of a ‘foetal gene programme’. The Mesenchyme homeobox 1 (Meox1) gene is one of the foetal programme genes. Meox1 may play a role in embryonic development, but its regulation of pathological hypertrophy is not known. Therefore, this study investigated the effect of Meox1 on pathological hypertrophy, including familial and pressure overload-induced hypertrophy, and its potential mechanism of action.Methods and resultsMeox1 expression was markedly down-regulated in the wild-type adult mouse heart with age, and expression was up-regulated in heart tissues from familial dilated cardiomyopathy (FDCM) mice of the cTnTR141W strain, familial hypertrophic cardiomyopathy (FHCM) mice of the cTnTR92Q strain, pressure overload-induced HF mice, and hypertrophic cardiomyopathy (HCM) patients. Echocardiography, histopathology, and hypertrophic molecular markers consistently demonstrated that Meox1 overexpression exacerbated the phenotypes in FHCM and in mice with thoracic aorta constriction (TAC), and that Meox1 knockdown improved the pathological changes. Gata4 was identified as a potential downstream target of Meox1 using digital gene expression (DGE) profiling, real-time PCR, and bioinformatics analysis. Promoter activity data and chromatin immunoprecipitation (ChIP) and Gata4 knockdown analyses indicated that Meox1 acted via activation of Gata4 transcription.ConclusionMeox1 accelerated decompensation via the downstream target Gata4, at least in part directly. Meox1 and other foetal programme genes form a highly interconnected network, which offers multiple therapeutic entry points to dampen the aberrant expression of foetal genes and pathological hypertrophy.

scholarly journals Single molecule kinetics in the familial hypertrophic cardiomyopathy D166V mutant mouse heart

2010 ◽  
Vol 48 (5) ◽  
pp. 989-998 ◽  
Author(s):  
Priya Muthu ◽  
Prasad Mettikolla ◽  
Nils Calander ◽  
Rafal Luchowski ◽  
Ignacy Gryczynski ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Single Molecule ◽  
Mutant Mouse ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Mouse Heart

scholarly journals Myricetin Alleviates Pathological Cardiac Hypertrophy via TRAF6/TAK1/MAPK and Nrf2 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Hai-han Liao ◽  
Nan Zhang ◽  
Yan-yan Meng ◽  
Hong Feng ◽  
Jing-jing Yang ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Mapk Signaling ◽  
Neonatal Rat ◽  
Mouse Heart ◽  
Pathological Cardiac Hypertrophy ◽  
Pathological Hypertrophy ◽  
Nrf2 Signaling Pathway

Myricetin (Myr) is a common plant-derived polyphenol and is well recognized for its multiple activities including antioxidant, anti-inflammation, anticancer, and antidiabetes. Our previous studies indicated that Myr protected mouse heart from lipopolysaccharide and streptozocin-induced injuries. However, it remained to be unclear whether Myr could prevent mouse heart from pressure overload-induced pathological hypertrophy. Wild type (WT) and cardiac Nrf2 knockdown (Nrf2-KD) mice were subjected to aortic banding (AB) surgery and then administered with Myr (200 mg/kg/d) for 6 weeks. Myr significantly alleviated AB-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction in both WT and Nrf2-KD mice. Myr also inhibited phenylephrine- (PE-) induced neonatal rat cardiomyocyte (NRCM) hypertrophy and hypertrophic markers’ expression in vitro. Mechanically, Myr markedly increased Nrf2 activity, decreased NF-κB activity, and inhibited TAK1/p38/JNK1/2 MAPK signaling in WT mouse hearts. We further demonstrated that Myr could inhibit TAK1/p38/JNK1/2 signaling via inhibiting Traf6 ubiquitination and its interaction with TAK1 after Nrf2 knockdown in NRCM. These results strongly suggested that Myr could attenuate pressure overload-induced pathological hypertrophy in vivo and PE-induced NRCM hypertrophy via enhancing Nrf2 activity and inhibiting TAK1/P38/JNK1/2 phosphorylation by regulating Traf6 ubiquitination. Thus, Myr might be a potential strategy for therapy or adjuvant therapy for malignant cardiac hypertrophy.

scholarly journals Regional dysfunction correlates with myofiber disarray in transgenic mice with ventricular expression ofras

2000 ◽  
Vol 278 (3) ◽  
pp. H898-H906 ◽  
Author(s):  
William J. Karlon ◽  
Andrew D. McCulloch ◽  
James W. Covell ◽  
John J. Hunter ◽  
Jeffrey H. Omens
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Human Subjects ◽  
Surface Strain ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Mouse Heart ◽  
Surface Shear ◽  
Tissue Sections ◽  
Heart Preparation ◽  
Regional Dysfunction ◽  
The Right

A hallmark of certain cardiac diseases such as familial hypertrophic cardiomyopathy is focal myofiber disarray. Regional ventricular dysfunction occurs in human subjects with hypertrophic cardiomyopathy; however, no direct evidence exists to correlate regional dysfunction with myofiber disarray. We used a transgenic mouse, which exhibits regional myofiber disarray via ventricular expression of the human oncogene ras, to investigate the relationship between myofiber disarray and septal surface strain. An isolated ejecting mouse heart preparation was used to record deformation of markers on the septal surface and to determine nonhomogeneous septal surface strain maps. Myofiber disarray made in histological tissue sections was correlated with gradients in surface systolic shortening. Significantly smaller maximum principal shortening was associated with disarray located near the right ventricle (RV) septal surface. There was also significantly smaller surface shear strain associated with disarray located either near the RV surface or at the midwall. Because surface shear is a local indicator of torsion, we conclude that myofiber disarray is associated with reduced septal torsion and reduced surface shortening.

scholarly journals Single Molecule Kinetics in the Familial Hypertrophic Cardiomyopathy RLC-R58Q Mutant Mouse Heart

2010 ◽  
Vol 98 (3) ◽  
pp. 715a
Author(s):  
Prasad Mettikolla ◽  
Rafal Luchowski ◽  
Shande Chen ◽  
Zygmunt Gryczynski ◽  
Ignacy Gryczynski ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Single Molecule ◽  
Mutant Mouse ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Mouse Heart

Tenascin-C enhances fibrosis and hypertrophy during pressure overload in the mouse heart

2014 ◽  
Vol 62 (S 01) ◽  
Author(s):  
E. Dzilic ◽  
M. Kreibich ◽  
F. Nagel ◽  
D. Santer ◽  
P. Moser ◽  
...  
Keyword(s):  
Pressure Overload ◽  
Mouse Heart ◽  
Tenascin C

Role of Cardiac MRI in Detecting Familial Hypertrophic Cardiomyopathy: Review

2016 ◽  
Vol 1 (1) ◽  
pp. 4
Author(s):  
Marymol Koshy ◽  
Bushra Johari ◽  
Mohd Farhan Hamdan ◽  
Mohammad Hanafiah
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Magnetic Resonance ◽  
Genetic Disorder ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Non Invasive ◽  
Wide Range ◽  
Proper Diagnosis ◽  
Magnetic Resonance Imaging Mri ◽  
Potential Use

Hypertrophic cardiomyopathy (HCM) is a global disease affecting people of various ethnic origins and both genders. HCM is a genetic disorder with a wide range of symptoms, including the catastrophic presentation of sudden cardiac death. Proper diagnosis and treatment of this disorder can relieve symptoms and prolong life. Non-invasive imaging is essential in diagnosing HCM. We present a review to deliberate the potential use of cardiac magnetic resonance (CMR) imaging in HCM assessment and also identify the risk factors entailed with risk stratification of HCM based on Magnetic Resonance Imaging (MRI).

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