PGAM1 deficiency ameliorates myocardial infarction remodeling by targeting TGF-β via the suppression of inflammation, apoptosis and fibrosis

Wu, Yueheng; Chen, Shaoxian; Wen, Pengju; Wu, Min; Wu, Yijing; Mai, Mingjie; Huang, Jilin

doi:10.1016/j.bbrc.2020.10.070

Cited by 12 publications

(12 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The role of the TGF-β/SMADs signaling pathway in apoptosis after MI The TGF-β/SMADs signaling pathway mediates multiple phenotypes, which not only plays a role in tissue repair but also apoptosis 464 . After MI, continuous ischemia and hypoxia will lead to activation of TGF-β, which leads to high expression of SMAD2/3, resulting in apoptosis of cardiomyocyte, and further aggravating myocardial injury 392,465 .…”

Section: Tgf-β/smads Signaling Pathway In MImentioning

confidence: 99%

Signaling pathways and targeted therapy for myocardial infarction

Zhang

Wang

et al. 2022

Sig Transduct Target Ther

350

117

View full text Add to dashboard Cite

Although the treatment of myocardial infarction (MI) has improved considerably, it is still a worldwide disease with high morbidity and high mortality. Whilst there is still a long way to go for discovering ideal treatments, therapeutic strategies committed to cardioprotection and cardiac repair following cardiac ischemia are emerging. Evidence of pathological characteristics in MI illustrates cell signaling pathways that participate in the survival, proliferation, apoptosis, autophagy of cardiomyocytes, endothelial cells, fibroblasts, monocytes, and stem cells. These signaling pathways include the key players in inflammation response, e.g., NLRP3/caspase-1 and TLR4/MyD88/NF-κB; the crucial mediators in oxidative stress and apoptosis, for instance, Notch, Hippo/YAP, RhoA/ROCK, Nrf2/HO-1, and Sonic hedgehog; the controller of myocardial fibrosis such as TGF-β/SMADs and Wnt/β-catenin; and the main regulator of angiogenesis, PI3K/Akt, MAPK, JAK/STAT, Sonic hedgehog, etc. Since signaling pathways play an important role in administering the process of MI, aiming at targeting these aberrant signaling pathways and improving the pathological manifestations in MI is indispensable and promising. Hence, drug therapy, gene therapy, protein therapy, cell therapy, and exosome therapy have been emerging and are known as novel therapies. In this review, we summarize the therapeutic strategies for MI by regulating these associated pathways, which contribute to inhibiting cardiomyocytes death, attenuating inflammation, enhancing angiogenesis, etc. so as to repair and re-functionalize damaged hearts.

show abstract

Section: Tgf-β/smads Signaling Pathway In MImentioning

confidence: 99%

Signaling pathways and targeted therapy for myocardial infarction

Zhang

Wang

et al. 2022

Sig Transduct Target Ther

350

117

View full text Add to dashboard Cite

show abstract

“…Mitochondrial energy metabolism, particularly aerobic glycolysis (known as the "Warburg effect"), has been a crucial area of research in cardiovascular disease for decades [4][5][6][7]. Research ndings have shown that a metabolic shift of increasing glucose oxidation provides bene cial effects in models of myocardial IR injury.…”

Section: Introductionmentioning

confidence: 99%

Scutellarin Protects against Myocardial Ischemia-Reperfusion Injury by Enhancing Aerobic Glycolysis via miR-34c-5p/ALDOA axis

Xiang

Qian

et al. 2023

Preprint

View full text Add to dashboard Cite

Ischemia–reperfusion (IR) injury is a serious concern in the treatment of coronary heart disease. Recently, aerobic glycolysis has shown potential benefits against IR injury. Scutellarin (Scu), a flavonoid found in Erigeron breviscapus has multiple potentially cardio-protective properties. In this study, we used hypoxia/reoxygenation (H/R) injury to mimic IR injury in vitro. First, we evaluated the protective effects of Scu against HR in H9c2 cells, which included inflammation damage, apoptosis injury and oxidative stress. Then, we verified the effects of Scu on Warburg effect in H9c2 cells under HR injury. The results indicated that Scu increased aerobic glycolysis by reducing pH, increasing lac, enhancing phosphofructokinase (PFK) activity, and elevating p-PKM2/PKM2 levels. Next, we built a panel of six lncRNAs and seventeen miRNAs that were reported to mediate the Warburg effect. Based on the results, miR-34c-5p was selected as the entry point for further experiments. Then, we found Scu could alleviate HR-induced elevation of miR-34c-5p. Up-regulation of miR-34c-5p could weaken the protective effects of Scu in cell viability, inflammatory damage and oxidative stress. The facilitation of Warburg effect by Scu was also reversed by miR-34c-5p mimic in H9c2 cells. Next, we found the mRNA and protein of ALDOA were reduced after HR injury, and these could be reversed by Scu. Downregulation of ALDOA or Mimic of miR-34c-5p could reduce the effects of Scu that maintained mRNA and protein levels of ALDOA. SiRNA of ALDOA could decrease anti-HR effects of Scu in H9c2 cell. Summarily, our study demonstrated that Scu provides cardio-protective effects against IR-induced myocardial cell injury by upregulating Warburg effect via miR-34c-5p/ALDOA pathway in H9c2 cell model.

show abstract

“…It is closely related to a variety of heart diseases [myocardial infarction, chronic heart failure (CHF), and atrial fibrillation]. Studies have shown that excessive physiological stress can lead to myocardial inflammation, fibrosis, and myocardial injury (3,4). A member of mitogen activated protein kinases (MAPKs) family, P38 MAPK, can activate nuclear factor-κB (NF-κB) by phosphorylating…”

Section: Introductionmentioning

confidence: 99%

Effects of Kangdaxin on myocardial fibrosis in heart failure with preserved ejection fraction rats

Wang¹,

Zhang²,

Qiao³

et al. 2022

J Thorac Dis

View full text Add to dashboard Cite

Background: This study aimed to explore the effects of Kangdaxin oral liquid on myocardial fibrosis in heart failure with preserved ejection fraction (HFpEF) rats.Methods: A total of 30 Sprague Dawley (SD) rats were randomly divided into 3 groups Sham operation group (Sham), HFpEF group (HFpEF), and HFpEF with drug intervention group (HFpEF + I). Rats in HFpEF + I group were given Kangdaxin oral liquid at a dose of 2.7 mL/(kg•d). After modeling or treatment, the value of E/A and E/e' in each group of rats were measured by echocardiography. The N-terminal pro b-type natriuretic peptide (NT-proBNP) level was determined by enzyme-linked immunosorbent assay (ELISA). Heart weight/body mass index (Hw/W) and left ventricular weight/body mass index (LVw/W) were calculated after the rats were sacrificed; the transforming growth factor-β1 (TGF-β1) protein expression level in cardiac tissue was detected by western blot.Results: Compared with sham group, the values of diastolic function item (E/A) and mitral annular early diastolic velocity (E/e') in HFpEF group were significantly decreased, and the level of NT-proBNP was significantly increased (P<0.05). Compared with HFpEF group, the value of E/A and E/e' in HF + I group were significantly increased, and the level of NT-proBNP was significantly decreased (P<0.05). Compared with sham group, the expression of TGF-β1 protein in heart tissue of HFpEF group were significantly increased (P<0.05). Compared with HFpEF group, the expression of TGF-β1 protein in HFpEF + I group were significantly decreased (P<0.05).Conclusions: Kangdaxin oral liquid has protective effect on heart in HFpEF rats, which can reduce the protein expression of TGF-β1 in the heart tissue of HFpEF rats. This may be a possible mechanism to inhibit myocardial fibrosis and improve cardiac diastolic function.

show abstract

PGAM1 deficiency ameliorates myocardial infarction remodeling by targeting TGF-β via the suppression of inflammation, apoptosis and fibrosis

Cited by 12 publications

References 33 publications

Signaling pathways and targeted therapy for myocardial infarction

Signaling pathways and targeted therapy for myocardial infarction

Scutellarin Protects against Myocardial Ischemia-Reperfusion Injury by Enhancing Aerobic Glycolysis via miR-34c-5p/ALDOA axis

Effects of Kangdaxin on myocardial fibrosis in heart failure with preserved ejection fraction rats

Contact Info

Product

Resources

About