Upregulated microRNA-210-3p Improves Sevoflurane-induced Protective Effect on Ventricular Remodeling in Rats With Myocardial Infarction by Inhibiting ADCY9

Mapping Intimacies ◽

10.21203/rs.3.rs-680443/v1 ◽

2021 ◽

Author(s):

Yahui Wu ◽

Taofu Wang ◽

Liang Qiao ◽

Hongqi Lin

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Protective Effect ◽

Adenylyl Cyclase ◽

Cause Of Death ◽

Myocardial Injury ◽

Ventricular Remodeling ◽

Cardiomyocyte Apoptosis

Abstract ObjectiveMyocardial infarction (MI) is a significant cause of death and disability, and sevoflurane (sevo) can protect myocardium in clinic. We aim to assess the effects of miR-210-3p on MI rats undergoing sevo treatment with the involvement of adenylyl cyclase type 9 (ADCY9).MethodsRat MI models were constructed by ligation of the left anterior descending and the modeled mice were respectively treated with sevo, miR-210-3p agomir/antagomir or overexpressed ADCY9. Then, miR-210-3p and ADCY9 expression, cardiac function, myocardial injury and fibrosis, and cardiomyocyte apoptosis in rats were evaluated. Target relation between miR-210-3p and ADCY9 was detected.ResultsMiR-210-3p was downregulated while ADCY9 was upregulated in MI rats. Sevo was able to promote cardiac function and attenuate myocardial injury and fibrosis, as well as cardiomyocyte apoptosis in MI rats. These effects of sevo were strengthened by miR-210-3p elevation while abolished by miR-210-3p inhibition. The role of elevated miR-210-3p in MI rats was reversed by overexpression of ADCY9.ConclusionUpregulated miR-210-3p improves sevo-induced protective effect on ventricular remodeling in rats with MI through inhibiting ADCY9.

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Neutrophil Elastase Deficiency Ameliorates Myocardial Injury Post Myocardial Infarction in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22020722 ◽

2021 ◽

Vol 22 (2) ◽

pp. 722

Author(s):

Yukino Ogura ◽

Kazuko Tajiri ◽

Nobuyuki Murakoshi ◽

DongZhu Xu ◽

Saori Yonebayashi ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Neutrophil Elastase ◽

Myocardial Injury ◽

Flow Cytometric Analysis ◽

Akt Signaling ◽

Border Zone ◽

Terminal Deoxynucleotidyl Transferase ◽

Deficient Mice

Neutrophils are recruited into the heart at an early stage following a myocardial infarction (MI). These secrete several proteases, one of them being neutrophil elastase (NE), which promotes inflammatory responses in several disease models. It has been shown that there is an increase in NE activity in patients with MI; however, the role of NE in MI remains unclear. Therefore, the present study aimed to investigate the role of NE in the pathogenesis of MI in mice. NE expression peaked on day 1 in the infarcted hearts. In addition, NE deficiency improved survival and cardiac function post-MI, limiting fibrosis in the noninfarcted myocardium. Sivelestat, an NE inhibitor, also improved survival and cardiac function post-MI. Flow cytometric analysis showed that the numbers of heart-infiltrating neutrophils and inflammatory macrophages (CD11b+F4/80+CD206low cells) were significantly lower in NE-deficient mice than in wild-type (WT) mice. At the border zone between intact and necrotic areas, the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells was lower in NE-deficient mice than in WT mice. Western blot analyses revealed that the expression levels of insulin receptor substrate 1 and phosphorylation of Akt were significantly upregulated in NE-knockout mouse hearts, indicating that NE deficiency might improve cardiac survival by upregulating insulin/Akt signaling post-MI. Thus, NE may enhance myocardial injury by inducing an excessive inflammatory response and suppressing Akt signaling in cardiomyocytes. Inhibition of NE might serve as a novel therapeutic target in the treatment of MI.

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Garcinoic Acid Improves Cardiac Function and Enhances Angiogenesis Following Myocardial Infarction

10.21203/rs.3.rs-146883/v1 ◽

2021 ◽

Author(s):

Hongyao Hu ◽

Wei Li ◽

Yanzhao Wei ◽

Hui Zhao ◽

Zhenzhong Wu ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Ventricular Remodeling ◽

Vehicle Group ◽

Potential Mechanism ◽

Garcinia Kola ◽

Angiogenic Proteins

Abstract Cardiac ischemia impairs angiogenesis in response to hypoxia, resulting in ventricular remodeling. Garcinoic acid (GA), the extraction from the plant garcinia kola, is validated to attenuate inflammatory response. However, the role of GA in heart failure (HF) and neovascularization after myocardial infarction (MI) is incompletely understood. The present study is striving to explore the role of GA and the potential mechanism of which in cardiac function after MI. SD rats were randomized into sham group, MI+vehicle group, and MI+GA group in vivo. Human umbilical endothelial cells (HUVECs) were cultured in vehicle or GA, and then additionally exposed to 2% hypoxia environment in vitro. MI rats displayed a dramatically reduced myocardial injury, cardiac function and vessel density in the peri-infarcted areas. GA delivery markedly improved cardiac performance and promoted angiogenesis. In addition, GA significantly enhanced tube formation in HUVECs under hypoxia condition. Furthermore, the expressions of pro-angiogenic factors HIF-1α, VEGF-A and bFGF, and pro-angiogenic proteins phospho-VEGFR2Tyr1175 and VEGFR2, as well as phosphorylation levels of Akt and eNOS were increased by GA treatment. In conclusion, GA preserved cardiac function after MI probably via promoting neovascularization. And the potential mechanism may be partially through upregulating the expressions of HIF-1α, VEGF-A, bFGF, phospho-VEGFR2Tyr1175 and VEGFR2 and activating the phosphorylations of Akt and eNOS.

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Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.280.6.h2726 ◽

2001 ◽

Vol 280 (6) ◽

pp. H2726-H2731 ◽

Cited By ~ 188

Author(s):

Eeva Palojoki ◽

Antti Saraste ◽

Anders Eriksson ◽

Kari Pulkki ◽

Markku Kallajoki ◽

...

Keyword(s):

Myocardial Infarction ◽

Ejection Fraction ◽

Ventricular Remodeling ◽

Apoptotic Cell ◽

Cell Loss ◽

Left Ventricular ◽

Cardiomyocyte Apoptosis ◽

Border Zones ◽

Terminal Deoxynucleotide Transferase

We investigated the role of cardiomyocyte apoptosis in the remodeling of the left ventricle from 24 h to 12 wk after myocardial infarction in the rat. Infarct size planimetry, quantification of cardiomyocyte apoptosis, terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) methodology, and echocardiography (left ventricular diastolic diameter and ejection fraction) were performed. Sham-operated animals showed low rates of cardiomyocyte apoptosis (0.03%) and no change in diastolic diameter or ejection fraction during the study. Twenty-four hours after infarction, TUNEL positivity was high in the infarct areas (1.4%) and border zones (4.9%). It declined to 0.34% ( P < 0.01 vs. sham) at 4 wk and 0.10% at 12 wk in the border zones. In the remote myocardium, cardiomyocyte apoptosis increased to 0.07% ( P = 0.03 vs. sham) on day 1 and remained on the same level up to 4 wk. The increase in diastolic diameter 1–4 wk after infarction correlated ( r = 0.60, P < 0.01) with cardiomyocyte apoptosis in the noninfarcted myocardium, which quantitatively contributed most (>50%) to the apoptotic cell loss by 4 wk.

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MicroRNA-322-5p Protects Against Myocardial Infarction through Targeting BTG2

10.21203/rs.3.rs-871695/v1 ◽

2021 ◽

Author(s):

Yang Ruan ◽

Shuai Meng ◽

Ruofei Jia ◽

Xiaojing Cao ◽

zening Jin

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

B Cell ◽

Rat Model ◽

Myocardial Injury ◽

Pathological Condition ◽

Current Paper ◽

Targeted Treatment ◽

Myocardial Tissue

Abstract Objective: A large cohort of studies have addressed the therapeutic importance of microRNA (miR) in the treatment of myocardial infarction (MI). The current paper gives prominence to the role of miR-322-5p in MI by regulating B-cell translocation gene 2 (BTG2).Methods: In a rat model of MI miR-322-5p and BTG2 expression was estimated. Adenovirus that altered miR-322-5p or BTG2 expression was injected into MI rats. After that, cardiac function, inflammation, myocardial injury, pathological condition, apoptosis, and the NF-κB pathway-related genes in the myocardial tissue of MI rats after targeted treatment were evaluated. The targeting relationship between miR-322-5p and BTG2 was assessed.Results: miR-322-5p was lowly expressed and BTG2 was highly expressed in the myocardial tissue of MI rats. Restored miR-322-5p improved cardiac function, relived inflammation and myocardial injury, suppressed pathological condition and apoptosis and inactivated NF-κB pathway in MI rats. BTG2 expression was negatively mediated by miR-322-5p. Overexpressed BTG2 rescued miR-322-5p-induced cardioprotection on MI rats.Conclusion: It is evident that miR-322-5p protects against MI through suppressing BTG2 expression.

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Overexpression of microRNA-135b-5p attenuates acute myocardial infarction injury through its anti-oxidant and anti-apptotic properties

Frigid Zone Medicine ◽

10.2478/fzm-2021-0011 ◽

2021 ◽

Vol 1 (2) ◽

pp. 85-94

Author(s):

Yanyan Liu ◽

Yahan Yu ◽

Xinyao Wang ◽

Guanqun Liu ◽

Xinda Yin ◽

...

Keyword(s):

Myocardial Infarction ◽

Protective Effect ◽

Target Genes ◽

Transient Receptor Potential ◽

Cardiomyocyte Apoptosis ◽

Ros Generation ◽

Transient Receptor Potential Vanilloid ◽

Transcriptional Level ◽

Apoptosis Protein

Abstract Objective Myocardial infarction (MI) remains the leading cause of morbidity and mortality due partly to the limited regenerative capacity of cardiomyocytes to replace cardiomyocyte lost due to apoptosis. Inhibiting cardiomyocyte apoptosis is recognized as an effective therapeutic approach for MI. MicroRNAs (miRNAs, miRs), which regulate target genes at the post-transcriptional level, play a significant role in the regulation of cardiovascular diseases such as MI. MicroRNA-135b (miR-135b) has a protective effect on cardiomyocytes. However, the role of miR-135b in cardiomyocyte apoptosis in infarct myocardium needs further clarification. Methods We generated α-MHC-miR-135b transgenic mice to investigate the role of miR-135b in myocardial injury after MI. MiR-135b mimic and negative control (NC) were transfected into H2O2-induced cardiomyocytes to evaluate the effect of overexpression of miR-135b on the levels of reactive oxygen species (ROS) and apoptosis. Results Our results showed that overexpression of miR-135b had protective effect on cardiomyocyte injury both in vivo and in vitro. MiR-135b inhibited cardiomyocyte apoptosis and ROS generation, downregulated proapoptosis proteins (cleaved-caspase-3 and Bax), and increased anti-apoptosis protein (Bcl-2). Moreover, miR-135b showed an inhibitory effect on apoptosis-related protein target transient receptor potential vanilloid-type 4 (TRPV4) cation channel. Conclusion MiR-135b might be considered a new molecular target for potential replacement therapy as antiapoptotic cardioprotection in the setting of MI.

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MicroRNA-26b inhibits cardiac remodeling after myocardial infarction by targeting ring finger protein 6 expression

Archives of Medical Science ◽

10.5114/aoms/130649 ◽

2021 ◽

Author(s):

Chun-mei Tang ◽

Qiang Su ◽

Hai-xia Zhao ◽

He-huan Sui ◽

Jing Liang ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Infarct Size ◽

Cardiac Remodeling ◽

Ring Finger ◽

Cardiomyocyte Apoptosis ◽

Luciferase Reporter ◽

Ring Finger Protein ◽

Finger Protein

IntroductionThis study aimed at determining the regulatory mechanism of miR-26b in myocardial infarction (MI)-induced cardiac remodeling through apoptosis.Material and methodsAn MI rat model was established by left coronary artery ligation. Microarray data were analyzed to distinguish differentially expressed genes in MI. miR-26b was found to be poorly expressed, whereas ring finger protein 6 (RNF6) was highly expressed in MI. Consequently, miR-26b was identified to target RNF6 using dual-luciferase reporter assay and bioinformatics prediction. Furthermore, rats injected with a lentiviral vector expressing miR-26b mimic and/or RNF6 were used to evaluate the role of miR-26b and RNF6 in regulating cardiac function, infarct size, and cardiomyocyte apoptosis.ResultsmiR-26b overexpression improved cardiac function and increased left ventricular end-diastolic and end-systolic diameters. Meanwhile, increased miR-26b expression decreased infarct size and cardiomyocyte apoptosis. Moreover, RNF6 overexpression counteracted the role of miR-26b in cardiac function. Additionally, an in vitro cell model illustrated that miR-26b upregulation could increase cell viability and reduce apoptosis, whereas RNF6 overexpression reversed its effect. We also found that the miR-26b mimic could negatively modulate RNF6 expression to inactivate the ERα/Bcl-xL axis.ConclusionsmiR-26b plays a protective role against cardiac remodeling after MI through the inactivation of the RNF6/ERα/Bcl-xL axis, proposing miR-26b and RNF6 as potential therapeutic targets for MI.

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