ArticleCardiovascular drugs and therapy2022
Ester Prodrugs of Malonate with Enhanced Intracellular Delivery Protect Against Cardiac Ischemia-Reperfusion Injury In Vivo.
Article in Cardiovascular drugs and therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- Spontaneous reperfusion enhances succinate concentration in peripheral blood from stemi patients but its levels does not correlate with myocardial infarct size or area at risk.Scientific reports · 2023Trial
- Mitochondrial oxidative stress, calcium and dynamics in cardiac ischaemia-reperfusion injury.The Journal of physiology · 2026Review
- Review
- Metabolic Intervention with Dimethyl Malonate Impairs Phagocytic Clearance but Fails to Protect Neurons.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial succinate transport is required for cardiac ischaemia/reperfusion injury.Cardiovascular research · 2026Article
- Activity-based CORedox biology · 2026Article
- Article
- The immune-cardiovascular metabolic circuitry in myocardial ischemia-reperfusion injury: from metabolic signal release to spatiotemporal reprogramming.Frontiers in immunology · 2026Review
- NEK7 couples SDHB to orchestrate respiratory chain electron transport homeostasis that impedes liver fibrosis.Nature communications · 2025Article
- Succinate Dehydrogenase Subunit A (SDHA) Mediated Microglia Extracellular Traps Formation Participating in Cerebral Ischemic Reperfusion Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Involvement of connexin 43 in myocardial ischemia-reperfusion injury.Cell and tissue research · 2025Review
- Local arterial administration of acidified malonate as an adjunct therapy to mechanical thrombectomy in ischemic stroke.Cardiovascular research · 2025Article
- Role of Gut Microbial Metabolites in Ischemic and Non-Ischemic Heart Failure.International journal of molecular sciences · 2025Review
- Pro-inflammatory macrophages produce mitochondria-derived superoxide by reverse electron transport at complex I that regulates IL-1β release during NLRP3 inflammasome activation.Nature metabolism · 2025Article
- Therapeutic strategies to ameliorate mitochondrial oxidative stress in ischaemia-reperfusion injury: A narrative review.Clinical science (London, England : 1979) · 2025Review
- Paracrine role of endothelial IGF-1 receptor in depot-specific adipose tissue adaptation in male mice.Nature communications · 2025Article
- Connexin 43 modulates reverse electron transfer in cardiac mitochondria from inducible knock-out Cx43Basic research in cardiology · 2024Article
- Malonate given at reperfusion prevents post-myocardial infarction heart failure by decreasing ischemia/reperfusion injury.Basic research in cardiology · 2024Article
- Long-Term Protective Effects of Succinate Dehydrogenase Inhibition during Reperfusion with Malonate on Post-Infarction Left Ventricular Scar and Remodeling in Mice.International journal of molecular sciences · 2024Article
- The Development of a Regulator of Human Serine Racemase for N-Methyl-D-aspartate Function.Biomedicines · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeMitochondrial reactive oxygen species (ROS) production upon reperfusion of ischemic tissue initiates the ischemia/reperfusion (I/R) injury associated with heart attack. During ischemia, succinate accumulates and its oxidation upon reperfusion by succinate dehydrogenase (SDH) drives ROS production. Inhibition of succinate accumulation and/or oxidation by dimethyl malonate (DMM), a cell permeable prodrug of the SDH inhibitor malonate, can decrease I/R injury. However, DMM is hydrolysed slowly, requiring administration to the heart prior to ischemia, precluding its administration to patients at the point of reperfusion, for example at the same time as unblocking a coronary artery following a heart attack. To accelerate malonate delivery, here we developed more rapidly hydrolysable malonate esters.
methodsWe synthesised a series of malonate esters and assessed their uptake and hydrolysis by isolated mitochondria, C2C12 cells and in mice in vivo. In addition, we assessed protection against cardiac I/R injury by the esters using an in vivo mouse model of acute myocardial infarction.
resultsWe found that the diacetoxymethyl malonate diester (MAM) most rapidly delivered large amounts of malonate to cells in vivo. Furthermore, MAM could inhibit mitochondrial ROS production from succinate oxidation and was protective against I/R injury in vivo when added at reperfusion.
conclusionsThe rapidly hydrolysed malonate prodrug MAM can protect against cardiac I/R injury in a clinically relevant mouse model.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.