scholarly journals Valsartan Regulates PI3K/AKT Pathways through lncRNA GASL1 to Improve Isoproterenol-Induced Heart Failure

2022 ◽  
Vol 2022 ◽  
pp. 1-8
Author(s):  
Jian Zhou ◽  
Xiujuan Duan ◽  
Jibing Wang ◽  
Yunhong Feng ◽  
Jiangyong Yuan
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Akt Pathway ◽  
Chain Reaction ◽  
Qrt Pcr ◽  
Polymerase Chain ◽  
And Function ◽  
Rat Tail

Objective. This study is aimed at determining the expression and function of the GASL1 and PI3K/AKT pathways in isoproterenol- (ISO-) induced heart failure (HF). To determine the moderating effect of valsartan (VAL) on the progression of ISO-induced HF and to elucidate the related mechanism. Materials and Methods. First, in in vivo experiment, we examined the effect of VAL on cardiac function in rats with ISO-induced HF. Similarly, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the effect of VAL on ISO-treated rat primary cardiomyocytes. Then, si-GASL1-transfected primary cardiomyocytes were constructed and Ad-si-GASL1 was injected through rat tail vein to achieve the effect of lowering GASL1 expression, so as to investigate the role of GASL1 in VAL’s treatment of ISO-induced HF. Results. In ISO-induced HF rat models, the GASL1 decreased while PI3K and p-AKT expressions were abnormally elevated and cardiac function deteriorated, and VAL was able to reverse these changes. In primary cardiomyocytes, ISO induces apoptosis of cardiomyocytes, and expression of GASL1 decreased while PI3K and p-AKT were abnormally elevated, which can be reversed by VAL. The transfection of primary cardiomyocytes with si-GASL1 confirmed that GASL1 affected the expression of PI3K, p-AKT, and the apoptosis of primary cardiomyocytes. Rat myocardium injected with Ad-si-GASL1 was found to aggravate the cardiac function improved by VAL. Conclusions. This study was the first to confirm that VAL improves ISO-induced HF by regulating the PI3K/AKT pathway through GASL1. And this study demonstrated a significant correlation between HF, VAL, GASL1, and the PI3K/AKT pathway.

MicroRNA expression profile in RAW264·7 macrophage cells exposed toEchinococcus multilocularismetacestodes

Parasitology ◽  
2017 ◽  
Vol 145 (3) ◽  
pp. 416-423 ◽  
Author(s):  
XIAOLA GUO ◽  
YADONG ZHENG
Keyword(s):  
Immune Responses ◽  
Treatment Time ◽  
Noncoding Rnas ◽  
Mirna Biogenesis ◽  
Sequencing Data ◽  
Chain Reaction ◽  
Expression Levels ◽  
Polymerase Chain ◽  
And Function

SUMMARYMicroRNAs (miRNAs) are short noncoding RNAs, involved in the regulation of parasite diseases. However, a role of miRNAs inEchinococcus multilocularisinfection remains largely unknown. In this study, we first found the expression levels of key genes involved in miRNA biogenesis and function, includingAgo2,Xpo5,Tarbp2andDgcR8, were obviously altered in the macrophage RAW264·7 cells exposed toE. multilocularismetacestodes. Compared with the control, 18 and 32 known miRNAs were found to be differentially expressed (P< 0·05 and fold change >2) in the macrophages exposed toE. multilocularismetacestodes for 6 and 12 h, respectively. Among these, several are known to be involved in regulating cytokine activities and immune responses. Quantitative real-time polymerase chain reaction results showed that the expression of nine selected miRNAs was consistent with the sequencing data at each treatment time points. Moreover, there were statistically significant correlations between the expression levels of miRNAs and their corresponding targeted genes. Our data give us some clues to pinpoint a role of miRNAs in the course of infection and immunity ofE. multilocularis.

Abstract 381: Mcur1 is a Potential Target to Modulate Cardiac Contractility and Alleviate Cardiac Function During Heart Failure

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Rajika Roy ◽  
Santhanam Shanmughapriya ◽  
Xueqian Zhang ◽  
Jianliang Song ◽  
Dhanendra Tomar ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Contractile Function ◽  
Cardiac Contractility ◽  
Pressure Overload ◽  
Dominant Negative ◽  
Selective Channel

Cardiac contractility is regulated by the intracellular Ca 2+ concentration fluxes which are actively regulated by multiple channels and transporters. Ca 2+ uptake into the mitochondrial matrix is precisely controlled by the highly Ca 2+ selective channel, Mitochondrial Calcium Uniporter (MCU). Earlier studies on the cardiac-specific acute MCU knockout and a transgenic dominant-negative MCU mice have demonstrated that mitochondrial Ca 2+ ( m Ca 2+ ) signaling is necessary for cardiac ‘‘fight-or-flight’’ contractile response, however, the role of m Ca 2+ buffering to shape global cytosolic Ca 2+ levels and affect E-C coupling, particularly the Ca 2+ transient, on a beat-to-beat basis still remains to be solved. Our earlier studies have demonstrated that loss of MCU Regulator 1 (MCUR1) in cardiomyocytes results in the impaired m Ca 2+ uptake. We have now employed the cardiac-specific MCUR1 knockout mouse to dissect the precise role of MCU in regulating cytosolic Ca 2+ transients associated with excitation-contraction (E-C) coupling and cardiac function. Results from our studies including the in vivo analyses of cardiac physiology during normal and pressure-overloaded mouse models and in vitro experiments including single-cell cardiac contractility, calcium transients, and electrophysiology measurements demonstrate that MCUR1/MCU regulated m Ca 2+ buffering in cardiomyocytes, although insignificant under basal condition, becomes critical in stress induced conditions and actively participates in regulating the c Ca 2+ transients. Also, the ablation of MCUR1 in cardiomyocytes during stress conditions prevents m Ca 2+ overload and subsequent mROS overproduction. Our data indicate that MCUR1 ablation offers protection against pressure-overload cardiac hypertrophy. In summary, our results provide critical insights into the mechanisms by which the MCU channel contributes in regulating the contractile function of the cardiomyocytes and the role of m Ca 2+ in the development and progression of heart failure.

Abstract 295: Enhanced Cardiac Function And Lower Circulating Aldosterone Levels In βArrestin1 Knockout Mice During Post-myocardial Infarction Heart Failure Progression

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Anastasios Lymperopoulos ◽  
Giuseppe Rengo ◽  
Erhe Gao ◽  
Ashley Siryk ◽  
Samalia Dabul ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Underlying Mechanism ◽  
Post Myocardial Infarction ◽  
Aldosterone Production ◽  
Heart Failure Progression ◽  
Adverse Remodeling ◽  
And Function

Introduction: Chronic heart failure (HF) is characterized by enhanced circulating cardiotoxic hormones, among the most prominent of which is aldosterone, which contributes to the increased morbidity and mortality of the disease by promoting cardiac adverse remodeling post-myocardial infarction (MI). Cardiac β-adrenergic receptor (ΑR) desensitization and downregulation are a hallmark abnormality in HF at the molecular level and are due to the concerted action of cardiac G protein-coupled receptor kinase-2 (GRK2), together with its co-factors in receptor desensitization, the βarrestins (βarrs). We have also recently established that βarr1 promotes angiotensin II-dependent aldosterone production in the adrenal cortex, and this leads to elevated circulating aldosterone levels in vivo, both under normal conditions and during post-MI HF progression. Hypothesis: Herein, we sought to investigate the effects of genetically deleting βarr1 on post-MI cardiac function and hyperaldosteronic status in mice progressing to HF. Methods: We uitilized the βarr1KO mouse model and studied these mice at 4 weeks after surgically induced MI, in parallel with C57/B6 wild type (WT) controls. Cardiac function was assessed by echocardiography and in vivo catheterization. Plasma aldosterone was measured by ELISA. Results: Cardiac function is markedly improved in βarr1KO`s at 4 weeks post-MI, as evidenced by increased ejection fraction compared to WT mice (41.5 + 2.8 % vs. 21.8 + 2.4 %, respectively, n=9, p<0.0001) and increased isoproterenol-induced contractility. Additionally, cardiac dimensions are significantly reduced compared to WT`s, indicating attenuation of adverse cardiac remodeling. Importantly, plasma circulating aldosterone levels are significantly lowered and cardiac βAR signaling and function appear elevated in post-MI βarr1KO`s compared to control WT`s. Conclusions: Genetic deletion of βarr1 substantially improves cardiac function, adverse remodeling, hyperaldosteronism, and cardiac βAR function during post-MI HF progression. The underlying mechanism is attenuation of both cardiac βAR desensitization/downregulation and adrenal aldosterone production, which is βarr1-dependent.

Abstract P108: Circulating Matrix Metalloproteinase-2 Invades the Heart and Causes Heart Failure

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Alejandro F Prado ◽  
Aline Azevedo ◽  
Cibele M Prado ◽  
Larissa Pernomian ◽  
Laena Pernomian ◽  
...  
Keyword(s):  
Heart Failure ◽  
Catalytic Domain ◽  
Heart Function ◽  
Matrix Metalloproteinase 2 ◽  
Saline Control ◽  
Function Loss ◽  
And Function ◽  
Tgf Β1

Background: An increase in MMP-2 levels is reported in heart failure (HF). However the role of MMP-2 in the pathogenesis of HF remains unclear. The aim of the present study was to determine the effect of increased circulating levels of MMP-2 on heart morphology and function. Methods and Results: Purified MMP-2 catalytic domain fused to GFP (catMMP-2/GFP) or saline (control) was injected into 11-wk-old male C57BL/6 mice for four weeks. The fluorescent active protein was tracked in vivo and homed in the heart. Cardiomyocyte diameter not changed between groups (catMMP-2/GFP: 11.37 ± 0.25 μm, n=7; Control: 11.38 ± 0.13 μm, n=7; P =0.97). On the other hand, fibrosis increased in the hearts of catMMP-2/GFP mice (0.82 ± 0.05% area/field, n=7 vs Control: 0.58 ± 0.02% area/field, n=7; P< 0.05). Apoptotic stained nuclei in the left ventricle (LV) of catMMP-2/GFP injected-mice amounted to 7.24%, n=4, P<0,05, whilst the LV of control animals only exhibited 0.27%, n=4. catMMP-2/GFP localized in the heart interstitium, where increased proteolytic activity (15.13 ± 1.33 U, n=5 vs Control: 9.70 ± 0.42 U, n=5; P <0.05). Hearts of catMMP-2/GFP mice showed 25% decrease in cardiac output (13 ± 1 mL/min, n=9 vs Control: 17 ± 1 mL/min, n=9), 30% decrease in ejection fraction (40 ± 2 %, n=9 vs Control: 56 ± 2 %, n=9) and stroke volume (28 ± 2 μL, n=9 vs Control: 40 ± 2 μL, n=9), and 34% decrease in fractional shortening (18 ± 1 %, n=9 vs Control: 28 ± 1 %, n=9) ( P <0.05 for all data).Western blotting showed 40% decrease in N-cadherin in animals that received catMMP-2/GFP (0.53 ± 0.08 U, n=6 vs control: 0.89 ± 0.11 U, n=6; P <0.05). Expression of signaling proteins also changed in LV of catMMP-2/GFP mice: TGF-β1 expression increased by 30% (0.60 ± 0.07 U, n=7 vs control: 0.40 ± 0.05 U, n=7, P<0,05), pAkt/Akt decreased by 40% (0.46 ± 0.05 U, n=7 vs control: 0.76 ± 0.11 U, n=7; P <0.05), pSMAD2/total SMAD2 ratio increased (1.88 ± 0.22 U, n=6 vs control: 0.93±0.12 U, n=6, P<0,05), and pSMAD3/total SMAD3 ratio increased (1.24 ± 0.22 U, n=7 vs control: 0.33 ± 0.07 U, n=7; P <0.05). Conclusions: Circulating active MMP-2 homing to the heart interstitium degrades N-cadherin and induces TGF-β1 overexpression, leading to apoptosis, and fibrosis. This mechanism may account for heart function loss when plasma levels of MMP-2 increase.

scholarly journals Negative feedback of SNRK to circ-SNRK regulates cardiac function post-myocardial infarction

2021 ◽  
Author(s):  
Zhi-Yan Wang ◽  
Xiao-Xiao Liu ◽  
Yun-Fei Deng
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Negative Feedback ◽  
Atp Synthesis ◽  
Protective Role ◽  
Splicing Regulator ◽  
Mitochondrial Efficiency

AbstractA limited delivery of oxygen and metabolic substrate to the heart caused by myocardial infarction (MI) impairs the cardiac function, and often results in heart failure. Here, we identified a circRNA (circ-SNRK) from SNRK (sucrose nonfermenting 1-related kinase, which can increase the cardiac mitochondrial efficiency) in cardiomyocytes (CMs). Circ-SNRK can sponge the miR-33 and in turn improved the ATP synthesis via SNRK, proving the existence of circ-SNRK - miR-33 - SNRK axis. Furthermore, we found that protein NOVA1 (NOVA alternative splicing regulator 1) could accelerate the circ-SNRK formation; a cleaved peptide (~55 kDa) from SNRK enters the nucleus and blocks the cyclization of circ-SNRK via binding to NOVA1. The aforementioned negative feedback of SNRK to circ-SNRK limited the SNRK at a proper level, and inhibited the protective role of circ-SNRK in ischemic heart. In addition, our in vivo experiment indicated that the overexpression of exogenic circ-SNRK could break this loop and improves the cardiac function post-MI in rats. Together, our results demonstrated that the negative loop of circ-SNRK with SNRK regulates the energy metabolism in CMs, thus might be a potential therapeutic target for heart failure.

Lysine-specific demethylase 2A expression is associated with cell growth and cyclin D1 expression in colorectal adenocarcinoma

2018 ◽  
Vol 33 (4) ◽  
pp. 407-414 ◽  
Author(s):  
Lin-Lin Cao ◽  
Changzheng Du ◽  
Hangqi Liu ◽  
Lin Pei ◽  
Li Qin ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cyclin D1 ◽  
Colorectal Adenocarcinoma ◽  
Chain Reaction ◽  
Adenocarcinoma Cell ◽  
Lysine Specific Demethylase ◽  
Adenocarcinoma Cells ◽  
Polymerase Chain ◽  
And Function

Objective: Lysine-specific demethylase 2A (KDM2A), a specific H3K36me1/2 demethylase, has been reported to be closely associated with several types of cancer. In this study, we aimed to investigate the expression and function of KDM2A in colorectal adenocarcinoma. Methods: A total of 215 colorectal adenocarcinoma specimens were collected, and then subjected to immunohistochemistry assay to evaluate the expression levels of KDM2A, cyclin D1 and other proteins in colorectal adenocarcinoma tissues. Real-time polymerase chain reaction, Western blot, and other molecular biology methods were used to explore the role of KDM2A in colorectal adenocarcinoma cells. Results: In this study, we report that the expression level of KDM2A is high in colorectal adenocarcinoma tissues, and this high expression promotes the proliferation and colony formation of colorectal adenocarcinoma cells, as demonstrated by KDM2A knockdown experiments. In addition, the expression of KDM2A is closely associated with cyclin D1 expression in colorectal adenocarcinoma tissues and cell lines. Conclusions: Our study reveals a novel role for high-expressed KDM2A in colorectal adenocarcinoma cell growth, and that the expression of KDM2A is associated with that of cyclin D1 in colorectal adenocarcinoma.

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