scholarly journals GW29-e0363 Aortic Constriction Induces Cardiac Hypertrophy Via The (Pro)Renin Receptor And Plc-Β3 Signaling Pathway

2018 ◽  
Vol 72 (16) ◽  
pp. C13
Author(s):  
Yanling Zhang ◽  
Chuanjun Liu ◽  
Aihuan Zhang ◽  
Jingjun Zhang ◽  
Junyan Wu ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Aortic Constriction

P1615HECT-Type Ubiquitin E3 Ligase ITCH attenuates cardiac hypertrophy by suppressing Wnt signaling pathway

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Goto ◽  
Y Otaki ◽  
T Watanabe ◽  
T Aono ◽  
K Watanabe ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
E3 Ligase ◽  
Pressure Overload ◽  
Aortic Constriction ◽  
Ubiquitin E3 Ligase ◽  
Ubiquitin Proteasome ◽  
Canonical Wnt ◽  
Interfering Rna

Abstract Background The homologous to the E6-AP carboxyl terminus (HECT)–type ubiquitin E3 ligase ITCH is an enzyme that plays an important role in ubiquitin proteasomal protein degradation. Dishevelled proteins (Dvl1, Dvl2 and Dvl3), which are involved in canonical Wnt/β catenin signaling pathway, play a role in cardiac hypertrophy. Purpose The aim of this study was to examine whether ITCH interacts with Dvls and prevents cardiac hypertrophy induced by pressure overload. Methods and results We confirmed the protein interaction between ITCH and Dvls in cardiomyocytes. Overexpression of ITCH decreased protein expression levels of Dvls, phospho-GSK3β and β-catenin. Conversely, knockdown of ITCH using small interfering RNA augmented canonical Wnt/β catenin signaling pathway. Thoracic transverse aortic constriction (TAC) was performed in transgenic mice with cardiac-specific overexpression of ITCH (ITCH-Tg) and wild-type (WT) mice. The canonical Wnt/β catenin signaling pathway was inhibited and cardiac hypertrophy was attenuated in ITCH-Tg mice compared with WT mice after TAC. Overexpression of ITCH in cardiomyocytes Conclusion We demonstrated that ITCH targets Dvls for ubiquitin-proteasome degradation in cardiomyocytes and ameliorates cardiac hypertrophy by suppressing canonical Wnt/β catenin signaling pathway.

scholarly journals Inhibition of the canonical Wnt signaling pathway by a β-catenin/CBP inhibitor prevents heart failure by ameliorating cardiac hypertrophy and fibrosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thanachai Methatham ◽  
Shota Tomida ◽  
Natsuka Kimura ◽  
Yasushi Imai ◽  
Kenichi Aizawa
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Left Ventricular ◽  
Cardiac Wall ◽  
Macrophage Marker ◽  
Glycolysis Pathway ◽  
Canonical Wnt ◽  
Macrophage Accumulation

AbstractIn heart failure (HF) caused by hypertension, the myocyte size increases, and the cardiac wall thickens. A low-molecular-weight compound called ICG001 impedes β-catenin-mediated gene transcription, thereby protecting both the heart and kidney. However, the HF-preventive mechanisms of ICG001 remain unclear. Hence, we investigated how ICG001 can prevent cardiac hypertrophy and fibrosis induced by transverse aortic constriction (TAC). Four weeks after TAC, ICG001 attenuated cardiac hypertrophy and fibrosis in the left ventricular wall. The TAC mice treated with ICG001 showed a decrease in the following: mRNA expression of brain natriuretic peptide (Bnp), Klf5, fibronectin, β-MHC, and β-catenin, number of cells expressing the macrophage marker CD68 shown in immunohistochemistry, and macrophage accumulation shown in flow cytometry. Moreover, ICG001 may mediate the substrates in the glycolysis pathway and the distinct alteration of oxidative stress during cardiac hypertrophy and HF. In conclusion, ICG001 is a potential drug that may prevent cardiac hypertrophy and fibrosis by regulating KLF5, immune activation, and the Wnt/β-catenin signaling pathway and inhibiting the inflammatory response involving macrophages.

Scutellarein protects against cardiac hypertrophy via suppressing TRAF2/NF-κB signaling pathway

2022 ◽  
Author(s):  
Xiujuan Shi ◽  
Yongjia Hu ◽  
Yuxiong Jiang ◽  
Jiawen Wu ◽  
Chen Zhang ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Signaling Pathway

Capn4 aggravates angiotensin II-induced cardiac hypertrophy by activating the IGF-AKT signaling pathway

2021 ◽  
Author(s):  
Yuanping Cao ◽  
Qun Wang ◽  
Caiyun Liu ◽  
Wenjun Wang ◽  
Songqing Lai ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Expression Patterns ◽  
Akt Signaling ◽  
Calpain Inhibitor ◽  
Ang Ii ◽  
Akt Signaling Pathway ◽  
Calpain Activity

Abstract Capn4 belongs to a family of calpains that participate in a wide variety of biological functions, but little is known about the role of Capn4 in cardiac disease. Here, we show that the expression of Capn4 was significantly increased in Angiotensin II (Ang II)-treated cardiomyocytes and Ang II-induced cardiac hypertrophic mouse hearts. Importantly, in agreement with the Capn4 expression patterns, the maximal calpain activity measured in heart homogenates was elevated in Ang II-treated mice, and oral coadministration of SNJ-1945 (calpain inhibitor) attenuated the total calpain activity measured in vitro. Functional assays indicated that overexpression of Capn4 obviously aggravated Ang II-induced cardiac hypertrophy, whereas Capn4 knockdown resulted in the opposite phenotypes. Further investigation demonstrated that Capn4 maintained the activation of the insulin-like growth factor (IGF)-AKT signaling pathway in cardiomyocytes by increasing c-Jun expression. Mechanistic investigations revealed that Capn4 directly bound and stabilized c-Jun, and knockdown of Capn4 increased the ubiquitination level of c-Jun in cardiomyocytes. Additionally, our results demonstrated that the antihypertrophic effect of Capn4 silencing was partially dependent on the inhibition of c-Jun. Overall, these data suggested that Capn4 contributes to cardiac hypertrophy by enhancing the c-Jun-mediated IGF-AKT signaling pathway and could be a potential therapeutic target for hypertrophic cardiomyopathy.

scholarly journals Bakuchiol protects against pathological cardiac hypertrophy by blocking NF-κB signaling pathway

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Zheng Wang ◽  
Lu Gao ◽  
Lili Xiao ◽  
Lingyao Kong ◽  
Huiting Shi ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Pressure Overload ◽  
Neonatal Rat ◽  
Oral Gavage ◽  
Aortic Banding ◽  
Rat Cardiomyocytes ◽  
Pathological Cardiac Hypertrophy ◽  
First Time

Bakuchiol (Bak), a monoterpene phenol isolated from the seeds of Psoralea corylifolia, has been widely used to treat a large variety of diseases in both Indian and Chinese folkloric medicine. However, the effects of Bak on cardiac hypertrophy remain unclear. Therefore, the present study was designed to determine whether Bak could alleviate cardiac hypertrophy. Mice were subjected to aortic banding (AB) to induce cardiac hypertrophy model. Bak of 1 ml/100 g body weight was given by oral gavage once a day from 1 to 8 weeks after surgery. Our data demonstrated for the first time that Bak could attenuate pressure overload-induced cardiac hypertrophy and could attenuate fibrosis and the inflammatory response induced by AB. The results further revealed that the effect of Bak on cardiac hypertrophy was mediated by blocking the activation of the NF-κB signaling pathway. In vitro studies performed in neonatal rat cardiomyocytes further proved that the protective effect of Bak on cardiac hypertrophy is largely dependent on the NF-κB pathway. Based on our results, Bak shows profound potential for its application in the treatment of pathological cardiac hypertrophy, and we believe that Bak may be a promising therapeutic candidate to treat cardiac hypertrophy and heart failure.

THE EFFECT OF DIFFERENT DEGREES OF SUBDIAPHRAGMATIC AORTIC CONSTRICTION ON HEART WEIGHT AND BLOOD PRESSURE OF NORMAL AND HYPOPHYSECTOMIZED RATS

1955 ◽  
Vol 33 (1) ◽  
pp. 985-994 ◽  
Author(s):  
Margaret Beznák
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Blood Pressure Response ◽  
Pressure Response ◽  
Heart Weight ◽  
Aortic Constriction ◽  
Hypophysectomized Rats ◽  
Intact Rats

The aortae of groups of normal and hypophysectomized rats were constricted with rings of five different sizes (0.93, 0.83, 0. 74, 0.71, and 0.63 mm. diameter). In normal rats constriction caused an increase in heart weight and blood pressure which was the greater the narrower the constriction. If constriction exceeded 0.74 mm., cardiac hypertrophy reached extremely high values, while the blood pressure was lower than in groups with less constriction. The blood pressure response to Adrenalin or Infundin increased in proportion to the degree of constriction down to 0.74 mm.; greater constriction reduced the response. In hypophysectomized rats no degree of aortic constriction produced hypertension or cardiac hypertrophy, yet the increase in blood pressure after Adrenalin or Infundin was as great as in the normal intact rats.

scholarly journals Leonurine Attenuates Pressure-Overload Cardiac Hypertrophy Induced By Abdominal Aortic Constriction In Rats

2021 ◽  
Author(s):  
Ding Xiaoli ◽  
Yuan Qingqing ◽  
Qian Haibing
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Ang Ii ◽  
Aortic Constriction ◽  
Qrt Pcr ◽  
Abdominal Aortic

Abstract Background: Myocardial hypertrophy occurs in many cardiovascular diseases. Leonurine (Leo) is commonly used for cardiovascular and cerebrovascular diseases. However, whether it can prevent cardiac hypertrophy is not known. The aim of this study was to investigate the effect and mechanism of Leonurine (Leo) against pressure-overload cardiac hypertrophy induced by abdominal aortic constriction (AAC) in rats. Methods: To answer this question, we prove it in the following way: Cardiac function was evaluated by hemodynamic; the left ventricle enlargement was measured by heart weight index (HWI) and left ventricular mass index (LVWI); myocardial tissue changes and myocardial cell diameter (MD) were determined by Hematoxylin and eosin (HE) staining; theβ-myosin heavy chain(β-MHC)and atrial natriuretic factor (ANF), which are recognized as a marker of cardiac hypertrophy, were determined by Real-time quantitative PCR (qRT-PCR), then another gene phospholipase C (PLC), inositol triphosphate (IP3), which associated with RAS were determined by Western blot(WB). angiotensin II (Ang II), angiotensin II type 1 receptor (AT1R) were determined by ELISA, WB and qRT-PCR methods. Finally, we measured the level of Ca2+ by microplate method and the protooncogene c-fos and c-myc mRNA in left ventricular myocardium by qRT-PCR.Results: Compare with control group, Leonurine can improve systolic dysfunction; inhibit the increase of left cardiac; inhibit myocardial cells were abnormally large and restrain the changes of cardiac histopathology; decrease the expression of β-MHC, ANF, Ang II, AT1R, c-fos and c-myc mRNA and the protein levels of PLC, IP3, AngII and AT1R in left ventricular myocardium, in addition, the content of Ca2+ also decrease. Conclusion: Therefore, Leonurine can inhibit cardiac hypertrophy induced by AAC and its effects may be associated with RAS.

A77 1726 (leflunomide) blocks and reverses cardiac hypertrophy and fibrosis in mice

2018 ◽  
Vol 132 (6) ◽  
pp. 685-699 ◽  
Author(s):  
Zhen-Guo Ma ◽  
Xin Zhang ◽  
Yu-Pei Yuan ◽  
Ya-Ge Jin ◽  
Ning Li ◽  
...  
Keyword(s):  
T Cell ◽  
Cardiac Hypertrophy ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Cardiac Fibrosis ◽  
Pressure Overload ◽  
Akt Signaling ◽  
Akt Signaling Pathway

T-cell infiltration and the subsequent increased intracardial chronic inflammation play crucial roles in the development of cardiac hypertrophy and heart failure (HF). A77 1726, the active metabolite of leflunomide, has been reported to have powerful anti-inflammatory and T cell-inhibiting properties. However, the effect of A77 1726 on cardiac hypertrophy remains completely unknown. Herein, we found that A77 1726 treatment attenuated pressure overload or angiotensin II (Ang II)-induced cardiac hypertrophy in vivo, as well as agonist-induced hypertrophic response of cardiomyocytes in vitro. In addition, we showed that A77 1726 administration prevented induction of cardiac fibrosis by inhibiting cardiac fibroblast (CF) transformation into myofibroblast. Surprisingly, we found that the protective effect of A77 1726 was not dependent on its T lymphocyte-inhibiting property. A77 1726 suppressed the activation of protein kinase B (AKT) signaling pathway, and overexpression of constitutively active AKT completely abolished A77 1726-mediated cardioprotective effects in vivo and in vitro. Pretreatment with siRNA targetting Fyn (si Fyn) blunted the protective effect elicited by A77 1726 in vitro. More importantly, A77 1726 was capable of blocking pre-established cardiac hypertrophy in mice. In conclusion, A77 1726 attenuated cardiac hypertrophy and cardiac fibrosis via inhibiting FYN/AKT signaling pathway.

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