Mitochondria-targeted ROS scavenger JP4-039 improves cardiac function in a post-myocardial infarction animal model and induces angiogenesis in vitro

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izdano v:PLoS One vol. 20, no. 4 (Apr 2025), p. e0320703
Glavni avtor: Teixeira, Rayane Brinck
Drugi avtorji: Albro, Jane H, Sabra, Mohamed, Abedin, Taslova, Tucker, Aja N, Raj Sidharth, Sellke, Frank W, Wipf, Peter, Abid, M Ruhul
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Public Library of Science
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024 7 |a 10.1371/journal.pone.0320703  |2 doi 
035 |a 3194483879 
045 2 |b d20250401  |b d20250430 
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100 1 |a Teixeira, Rayane Brinck 
245 1 |a Mitochondria-targeted ROS scavenger JP4-039 improves cardiac function in a post-myocardial infarction animal model and induces angiogenesis <i><b>in vitro</b></i> 
260 |b Public Library of Science  |c Apr 2025 
513 |a Journal Article 
520 3 |a BackgroundThis study aimed at evaluating the effects of JP4-039, a mitochondria-specific reactive oxygen species (mito-ROS) scavenger, on coronary angiogenesis and cardiac function in a post-myocardial infarction (MI) animal model.MethodsMice underwent ligation of the left anterior descending (LAD) artery to induce MI and received intraperitoneal (i.p.) injections of JP4-039 or vehicle (n=8 animals/group) three times/week for four weeks. Echocardiography for cardiac function and immunohistochemistry for Infarction area and capillary density were carried out. Angiogenic potential of endothelial cells (EC) was assessed by ex vivo tube formation using mouse heart EC (MHEC) and by aortic and atrial sprouting. Western blots were conducted using mouse cardiac tissue and lysates from HCAECs that were treated with or without JP4-039.ResultsCardiac function including ejection fraction, fractional shortening, and fractional area change were improved significantly in JP4-039-treated animals compared to the vehicle group. JP4-039-treated hearts demonstrated significant reduction in infarction size and increased capillary density in the ischemic area. These findings were consistent with increased ex vivo endothelial sprouting of the aortae and atrial tissue from the mice treated with JP4-039. Western blots using cardiac tissue lysates from JP4-039-treated animals showed decrease in phosphorylation of AMPKα at the Threonine 172, suggesting a plausible increase in the ATP:AMP ratio. Interestingly, JP4-039 increased expression of mitochondrial complexes I and IV and increased ATP synthesis in EC.ConclusionsJP4-039-mediated reduction in mito-ROS results in significantly increased coronary vascular density in ischemic myocardium, improved ATP synthesis, and recovery of post-MI cardiac function. Together, these results suggest that nitroxide nanodrug-mediated reduction in mito-ROS may help recover post-MI cardiac function. 
610 4 |a Nikon Instruments Inc 
651 4 |a United States--US 
651 4 |a Germany 
653 |a Mitochondria 
653 |a Aorta 
653 |a Heart 
653 |a Phosphorylation 
653 |a Cytochrome 
653 |a Nitroxide 
653 |a Heart failure 
653 |a Ischemia 
653 |a Hypoxia 
653 |a Reactive oxygen species 
653 |a Antioxidants 
653 |a Myocardial infarction 
653 |a Lysates 
653 |a Animal models 
653 |a Synthesis 
653 |a Density 
653 |a Echocardiography 
653 |a Myocardium 
653 |a Angiogenesis 
653 |a Homeostasis 
653 |a Animals 
653 |a Heart attacks 
653 |a Endothelial cells 
653 |a Coronary vessels 
653 |a Cardiovascular disease 
653 |a Immunohistochemistry 
653 |a Veins & arteries 
653 |a Cardiac function 
653 |a Western blotting 
653 |a Social 
700 1 |a Albro, Jane H 
700 1 |a Sabra, Mohamed 
700 1 |a Abedin, Taslova 
700 1 |a Tucker, Aja N 
700 1 |a Raj Sidharth 
700 1 |a Sellke, Frank W 
700 1 |a Wipf, Peter 
700 1 |a Abid, M Ruhul 
773 0 |t PLoS One  |g vol. 20, no. 4 (Apr 2025), p. e0320703 
786 0 |d ProQuest  |t Health & Medical Collection 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3194483879/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full Text  |u https://www.proquest.com/docview/3194483879/fulltext/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3194483879/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch