Introduction: Treatment with short hairpin RNA (shRNA) interference therapy targeting phosphodiesterase 5a after myocardial infarction (MI) has been shown to mitigate post-MI heart failure. We investigated the mechanisms that underpin the beneficial effects of PDE5a inhibition through shRNA on post-MI heart failure.
Methods: An adenoviral vector with an shRNA sequence inserted was adopted for the inhibition of phosphodiesterase 5a (Ad-shPDE5a) in vivo and in vitro. Myocardial infarction (MI) was induced in male C57BL/6J mice by left coronary artery ligation, and immediately after that, the Ad-shPDE5a was injected intramyocardially around the MI region and border areas.
Results: Four weeks post-MI, the Ad-shPDE5a-treated mice showed significant mitigation of the left ventricular (LV) dilatation and dysfunction compared to control mice. Infarction size and fibrosis were also significantly reduced in Ad-shPDE5a-treated mice. Additionally, Ad-shPDE5a treatment decreased the MI-induced inflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and transforming growth factor-β1, which was confirmed in vitro in Ad-shPDE5a transfected myofibroblasts cultured under oxygen glucose deprivation. Finally, Ad-shPDE5a treatment was found to activate the myocardial Akt signaling pathway in both in vivo and in vitro experiments.
Conclusion: These findings indicate that PDE5a inhibition by Ad-shPDE5a via the Akt signal pathway could be of significant value in the design of future therapeutics for post-MI heart failure.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692549 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145766 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Introduction: The infarcted heart is energetically compromised exhibiting a deficient production of adenosine triphosphate (ATP) and the ensuing impaired contractile function. Short-term blockade of the protein S100A9 improves cardiac performance in mice after myocardial infarction (MI). The implications upon ATP production during this process are not known.
View Article and Find Full Text PDFAssembly of ceria-Nrf2 nanoparticles as macrophage-targeting ROS scavengers protects against myocardial infarction.
Front Pharmacol
January 2025
The Sixth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, The Fifth Affiliated Hospital, Guangzhou, China.
Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide, and mitigating oxidative stress is crucial in managing MI. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in combating oxidative stress and facilitating cardiac remodeling post-MI. Here, we engineered Cerium oxide (CeO) nanoparticle-guided assemblies of ceria/Nrf2 nanocomposites to deliver Nrf2 plasmids.
View Article and Find Full Text PDFA New target of ischemic ventricular arrhythmias-ITFG2.
Eur J Pharmacol
January 2025
Department of Basic Medicine, Institute of Respiratory Diseases Xiamen Medical College, Xiamen Medical College, Xiamen, Fujian 361023, P. R. China; State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China. Electronic address:
ITFG2 is an intracellular protein known to modulate the immune response of T-cells. Our previous investigation revealed that ITFG2 specifically targets ATP5b to regulate ATP energy metabolism and maintain mitochondrial function, thereby protecting the heart from ischemic injury. However, the role of ITFG2 in ischemic ventricular arrhythmias and its underlying mechanisms have not been previously reported.
View Article and Find Full Text PDFDichloroacetate: A metabolic game-changer in alleviating macrophage inflammation and enhancing recovery after myocardial infarction.
Cell Signal
January 2025
Department of Cardiovascular Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China; Future Medical laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China. Electronic address:
Background: Dichloroacetate (DCA) has shown potential in modulating cellular metabolism and inflammation, particularly in cardiac conditions. This study investigates DCA's protective effects in a mouse model of myocardial infarction (MI), focusing on its ability to enhance cardiac function, reduce inflammation, and shift macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype.
Methods: An acute MI model was created using left anterior descending coronary artery ligation.
Microvessel co-transplantation improves poor remuscularization by hiPSC-cardiomyocytes in a complex disease model of myocardial infarction and type 2 diabetes.
Stem Cell Reports
January 2025
Toronto General Hospital Research Institute, University Health Network, 101 College St., Toronto, ON M5G 1L7, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Laboratory of Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Heart & Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, ON, Canada; Ajmera Transplant Center, University Health Network, Toronto, ON, Canada. Electronic address:
People with type 2 diabetes (T2D) are at a higher risk for myocardial infarction (MI) than age-matched healthy individuals. Here, we studied cell-based cardiac regeneration post MI in T2D rats modeling the co-morbid conditions in patients with MI. We recapitulated the T2D hallmarks and clinical aspects of diabetic cardiomyopathy using high-fat diet and streptozotocin in athymic rats, which were then subjected to MI and intramyocardial implantation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with or without rat adipose-derived microvessels (MVs).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!