Role of sodium-hydrogen exchange in cardiac hypertrophy and heart failure: a novel and promising therapeutic target

2001 ◽  
Vol 96 (4) ◽  
pp. 325-328 ◽  
Author(s):  
Morris Karmazyn
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Therapeutic Target ◽  
Hydrogen Exchange ◽  
Sodium Hydrogen ◽  
Promising Therapeutic Target

scholarly journals Osteopontin: A Promising Therapeutic Target in Cardiac Fibrosis

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1558 ◽  
Author(s):  
Iman Abdelaziz Mohamed ◽  
Alain-Pierre Gadeau ◽  
Anwarul Hasan ◽  
Nabeel Abdulrahman ◽  
Fatima Mraiche
Keyword(s):  
Heart Failure ◽  
Tissue Regeneration ◽  
Cardiac Remodeling ◽  
Therapeutic Target ◽  
Cardiac Fibrosis ◽  
Matricellular Protein ◽  
Physiological Conditions ◽  
Intracellular Signals ◽  
Promising Therapeutic Target

Osteopontin (OPN) is recognized for its significant roles in both physiological and pathological processes. Initially, OPN was recognized as a cytokine with pro-inflammatory actions. More recently, OPN has emerged as a matricellular protein of the extracellular matrix (ECM). OPN is also known to be a substrate for proteolytic cleavage by several proteases that form an integral part of the ECM. In the adult heart under physiological conditions, basal levels of OPN are expressed. Increased expression of OPN has been correlated with the progression of cardiac remodeling and fibrosis to heart failure and the severity of the condition. The intricate process by which OPN mediates its effects include the coordination of intracellular signals necessary for the differentiation of fibroblasts into myofibroblasts, promoting angiogenesis, wound healing, and tissue regeneration. In this review, we discuss the role of OPN in contributing to the development of cardiac fibrosis and its suitability as a therapeutic target.

scholarly journals Cardiac metabolism — A promising therapeutic target for heart failure

2018 ◽  
Vol 182 ◽  
pp. 95-114 ◽  
Author(s):  
Hannah Noordali ◽  
Brodie L. Loudon ◽  
Michael P. Frenneaux ◽  
Melanie Madhani
Keyword(s):  
Heart Failure ◽  
Therapeutic Target ◽  
Cardiac Metabolism ◽  
Promising Therapeutic Target

Role of sodium/hydrogen exchange in myocardial hypertrophy in vitro and in vivo

1992 ◽  
Vol 24 ◽  
pp. 60
Author(s):  
Toshifumi Kagiya ◽  
Masatsugu Hori ◽  
Seiji Takashima ◽  
Hiroshi Sato ◽  
Kunimitsu Iwai ◽  
...  
Keyword(s):  
Hydrogen Exchange ◽  
Myocardial Hypertrophy ◽  
Sodium Hydrogen

P1608Inhibition of GATA4 dimerization suppress hypertrophic responses

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Shimizu ◽  
Y Sunagawa ◽  
K Hara ◽  
A Hishiki ◽  
Y Katanasaka ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dna Binding ◽  
Cardiac Hypertrophy ◽  
Zinc Finger ◽  
Therapeutic Target ◽  
Transcriptional Activity ◽  
Luciferase Assay ◽  
Zinc Finger Motif ◽  
Zinc Finger Domain ◽  
Acetylation Site

Abstract Introduction Hypertrophic signals eventually reach the nuclei of cardiomyocytes, change patterns of gene expression, and cause the development of heart failure. During the development of heart failure, intrinsic histone acetyltransferase called p300 induce GATA4 acetylation. Acetylated GATA4 increases its DNA binding, up-regulates cardiac hypertrophic response genes, and lead to heart failure. A zinc finger protein, GATA4 is the transcription factor that expression level is high in heart. It has been reported that GATA1, the same GATA family, regulates transcriptional activity through its homo-dimerization. However, GATA4 homo-dimerization and its relationship to hypertrophic responses are still unknown. Purpose To clarify the relationship between GATA4 homo-dimerization and transcriptional activity and investigate whether inhibition of this homo-dimerization become therapeutic target for cardiac hypertrophy. Methods GST pull-down and DNA pull-down assay were performed using GST fusion full length and deletion mutants of GATA4 and biotin-conjugated ET-1 promoter probe including a GATA element. Recombinant C-zinc finger domain (256–326), including C-zinc finger motif (256–295) and acetylation site (308–326) was cross-linked using glutaraldehyde and subjected to silver staining. An expression plasmid with three GATA4-acetylation site mutant-conjugated with nuclear localization sequence (3xG4D) was constructed. Immunoprecipitation and western blotting were performed using nuclear extract from HEK293T cells expressing p300, GATA4, and 3xG4D. Luciferase assay was using ANF and ET-1 promoter sequences. Neonatal rat cultured cardiomyocyte expressed 3xG4D and then stimulated with phenylephrine (PE) for 48 hours. Next cardiomyocytes stained with α-actinin antibody and measured the cell surface area. Results The acetylation site of GATA4 was required for the dimerization of GATA4. But, C-zinc finger motif (256–295) and the acetylation site were required for the DNA binding. Recombinant C-zinc finger domain formed not only a homo-dimer but also a multimer. Co-expression of p300 increased the formation of homo-dimer as well as the acetylation of GATA4 in HEK293T cells. The GATA4 homo-dimer was disrupted by acetyl-deficient GATA4 or HAT-deficient p300 mutant. Overexpression of 3xG4D prevented the dimerization of GATA4, but not acetylation of GATA4. The result of luciferase assay showed that overexpression of 3xG4D prevented p300/GATA-induced ANF and ET-1 promoter activities. Furthermore, overexpression of 3xG4D inhibited phenylephrine-induced cardiomyocyte hypertrophy. Conclusions These results suggest that GATA4 dimerization may play an important role in hypertrophy-response gene activation. Thus, it is likely that inhabitation of GATA4 dimerization become therapeutic target for cardiac hypertrophy.

The Role of Grb14 in IGF1–PI3K Signalling and Cardiac Hypertrophy: A Potential Target for the Treatment of Heart Failure?

2009 ◽  
Vol 18 ◽  
pp. S303-S304
Author(s):  
K. Weeks ◽  
H. Kiriazis ◽  
N. Cemerlang ◽  
J.W. Tan ◽  
Z. Ming ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Potential Target ◽  
Pi3k Signalling

MicroRNA-26 Was Decreased in Rat Cardiac Hypertrophy Model and May Be a Promising Therapeutic Target

2013 ◽  
Vol 62 (3) ◽  
pp. 312-319 ◽  
Author(s):  
Zhen-hui Zhang ◽  
Jiao Li ◽  
Ben-rong Liu ◽  
Cheng-feng Luo ◽  
Qi Dong ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Therapeutic Target ◽  
Promising Therapeutic Target

scholarly journals Role of microRNAs in cardiac hypertrophy and heart failure

IUBMB Life ◽  
2009 ◽  
Vol 61 (6) ◽  
pp. 566-571 ◽  
Author(s):  
Nan Wang ◽  
Zhen Zhou ◽  
Xinghua Liao ◽  
Tongcun Zhang
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy
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