scholarly journals Sterile Inflammation as a Novel Therapeutic Target to Heart Failure

2021 ◽  
Vol 70 (2) ◽  
pp. 65-69
Author(s):  
Takeshi SUETOMI
Keyword(s):  
Heart Failure ◽  
Therapeutic Target ◽  
Sterile Inflammation ◽  
Novel Therapeutic

scholarly journals NLRP3 inflammasome as a novel therapeutic target for heart failure

2021 ◽  
Author(s):  
Shuangcui Wang ◽  
◽  
Jiaqi Zhang ◽  
Yuli Wang ◽  
Xijuan Jiang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Nlrp3 Inflammasome ◽  
Therapeutic Target ◽  
Novel Therapeutic

Abstract 297: Development of Molecular Targeted Therapy Against Right Ventricular Failure: Involvement in a Network of Immunocompetent Cells

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Shogo Ito ◽  
Shinsuke Yuasa ◽  
Jin Komuro ◽  
Mai Kimura ◽  
Dai Kusumoto ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ventricular Arrhythmia ◽  
Right Ventricular ◽  
Microarray Analysis ◽  
Pathway Analysis ◽  
Therapeutic Target ◽  
Immunocompetent Cells ◽  
Wild Type ◽  
Novel Therapeutic

Backgrounds: Right ventricular (RV) failure plays a critical role in right heart failure and left heart failure. However, there is no specific therapy developed for RV failure. To elucidate a novel therapeutic target against RV failure, we focus on RV specific genes to develop novel therapeutics for RV failure. Methods: Microarray analysis using several parts of adult murine heart was conducted and differentially expressed genes (DEGs) were applied to pathway analysis. Molecular mechanism was examined by using neonatal rat ventricular cardiomyocyte (NRVM) in vitro. To understand the function of target molecule in vivo, we induced RV failure by pulmonary artery constriction (PAC) in mice and inhibition experiments were performed using RV failure model. Results: In microarray analysis for RV, left ventricle and ventricular septum, 995 genes were extracted as DEGs in RV. Pathway analysis showed that alternative complement pathway-related genes were significantly up-regulated in RV. Moreover, complement factor D (Cfd) and C3a was a potential upstream factor attributable to unique feature of RV. Administration of C3a recombinant protein to NRVM phosphorylated several MAP kinases. In vivo, in C3KO PAC mice, RV dysfunction was significantly suppressed, and histological study showed that RV fibrosis was significantly suppressed. In wild type mice with PAC, administration of C3a receptor antagonist dramatically improved RV dysfunction and reduced RV fibrosis. Additionally, in vivo electrophysiological study revealed that the inducibility of ventricular arrhythmia was increased in wild type PAC mice, but ventricular arrhythmia was significantly attenuated in C3KO PAC mice. Furthermore, the expression of chemokine Ccl5 was enhanced in RV of wild type PAC mice, while Ccl5 was significantly attenuated in C3KO PAC mice. Conclusion: We revealed that complement C3a was highly produced in RV and chemical or genetical blockade of C3a ameliorates RV dysfunction and RV fibrosis in PAC mice. C3a was to be a potent bioactive protein for immunocompetent cells that played an important role in modulating cardiac function. Accordingly, we demonstrated that the blockade of C3a had a potential role for novel therapeutic target to RV failure.

scholarly journals Inter-atrial dyssynchrony contributes to heart failure symptoms in patients with preserved ejection fraction: a potential novel therapeutic target

2013 ◽  
Vol 34 (suppl 1) ◽  
pp. P2421-P2421
Author(s):  
L. Vannini ◽  
L. Gabrielli ◽  
B. Bijnens ◽  
L. Sanchis ◽  
N. Duchateau ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Therapeutic Target ◽  
Preserved Ejection Fraction ◽  
Novel Therapeutic

scholarly journals Binding Affinity of Calmodulin to Cardiac Ryanodine Receptor, as the Novel Therapeutic Target in the Pressure-overloaded Heart Failure

2014 ◽  
Vol 20 (10) ◽  
pp. S173
Author(s):  
Takayoshi Kato ◽  
Takeshi Yamamoto ◽  
Takako Maeda ◽  
Shigehiko Nishimura ◽  
Takeshi Suetomi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Binding Affinity ◽  
Ryanodine Receptor ◽  
Therapeutic Target ◽  
The Novel ◽  
Novel Therapeutic ◽  
Cardiac Ryanodine Receptor
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