دورية أكاديمية
Malonate given at reperfusion prevents post-myocardial infarction heart failure by decreasing ischemia/reperfusion injury.
| العنوان: | Malonate given at reperfusion prevents post-myocardial infarction heart failure by decreasing ischemia/reperfusion injury. |
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| المؤلفون: | Abe, Jiro, Vujic, Ana, Prag, Hiran A, Murphy, Michael P, Krieg, Thomas |
| المصدر: | Basic Res Cardiol ; ISSN:1435-1803 |
| بيانات النشر: | Springer |
| سنة النشر: | 2024 |
| المجموعة: | PubMed Central (PMC) |
| مصطلحات موضوعية: | Heart failure with reduced ejection fraction, Ischemia/reperfusion injury, Malonate, Mitochondria, Reactive oxygen species, Succinate |
| الوصف: | The mitochondrial metabolite succinate is a key driver of ischemia/reperfusion injury (IRI). Targeting succinate metabolism by inhibiting succinate dehydrogenase (SDH) upon reperfusion using malonate is an effective therapeutic strategy to achieve cardioprotection in the short term (< 24 h reperfusion) in mouse and pig in vivo myocardial infarction (MI) models. We aimed to assess whether inhibiting IRI with malonate given upon reperfusion could prevent post-MI heart failure (HF) assessed after 28 days. Male C57BL/6 J mice were subjected to 30 min left anterior coronary artery (LAD) occlusion, before reperfusion for 28 days. Malonate or without-malonate control was infused as a single dose upon reperfusion. Cardiac function was assessed by echocardiography and fibrosis by Masson's trichrome staining. Reperfusion without malonate significantly reduced ejection fraction (~ 47%), fractional shortening (~ 23%) and elevated collagen deposition 28 days post-MI. Malonate, administered as a single infusion (16 mg/kg/min for 10 min) upon reperfusion, gave a significant cardioprotective effect, with ejection fraction (~ 60%) and fractional shortening (~ 30%) preserved and less collagen deposition. Using an acidified malonate formulation, to enhance its uptake into cardiomyocytes via the monocarboxylate transporter 1, both 1.6 and 16 mg/kg/min 10 min infusion led to robust long-term cardioprotection with preserved ejection fraction (> 60%) and fractional shortening (~ 30%), as well as significantly less collagen deposition than control hearts. Malonate administration upon reperfusion prevents post-MI HF. Acidification of malonate enables lower doses of malonate to also achieve long-term cardioprotection post-MI. Therefore, the administration of acidified malonate upon reperfusion is a promising therapeutic strategy to prevent IRI and post-MI HF. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1007/s00395-024-01063-zTest; https://pubmed.ncbi.nlm.nih.gov/38864895Test |
| DOI: | 10.1007/s00395-024-01063-z |
| الإتاحة: | https://doi.org/10.1007/s00395-024-01063-zTest https://pubmed.ncbi.nlm.nih.gov/38864895Test |
| حقوق: | © 2024. The Author(s). |
| رقم الانضمام: | edsbas.BFBBDA64 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s00395-024-01063-z |
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