CD36 as a target for metabolic modulation therapy in cardiac disease

Glatz, Jan F. C.; Wang, Fang; Nabben, Miranda; Luiken, Joost J. F. P.

doi:10.1080/14728222.2021.1941865

Cited by 24 publications

(17 citation statements)

References 60 publications

(83 reference statements)

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“…NGR1 administration effectively improved the abnormal increase of CPT2 in ischemic myocardium ( Figure 6B ). CD36, as a dynamic gatekeeper of fatty acids, markedly declined in the ischemic myocardium, suggesting subdued β-oxidation ( Glatz et al, 2021 ). NGR1 significantly upregulated the expression of CD36 in the ischemic myocardium, which suggested that NGR1 partly restores β-oxidation ( Figure 6B ).…”

Section: Resultsmentioning

confidence: 99%

Notoginsenoside R1 Regulates Ischemic Myocardial Lipid Metabolism by Activating the AKT/mTOR Signaling Pathway

Wei

Yan

et al. 2022

Front. Pharmacol.

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Ischemic heart diseases are responsible for more than one-third of all deaths worldwide. Radix notoginseng is widely used to treat ischemic heart disease in China and other Asian countries, and notoginsenoside R1 (NGR1) is its characteristic and large-amount ingredient. However, the potential molecular mechanisms of NGR1 in improving ischemic heart diseases are unclear. In this study, we combined pharmacological evaluation with network pharmacology, myocardial proteomics, and conventional molecular dynamics (MD) simulation to explore the cardio-protection mechanisms of NGR1. Our results revealed that NGR1 improved the echocardiographic, tissue pathological, and serum biochemical perturbations in myocardial ischemic rats. The network pharmacology studies indicated that NGR1 mainly regulated smooth muscle cell proliferation, vasculature development, and lipid metabolism signaling, especially in the PI3K/AKT pathway. Myocardial proteomics revealed that the function of NGR1 was focused on regulating metabolic and energy supply processes. The research combined reverse-docked targets with differential proteins and demonstrated that NGR1 modulated lipid metabolism in ischemic myocardia by interacting with mTOR and AKT. Conventional MD simulation was applied to investigate the influence of NGR1 on the structural stabilization of the mTOR and AKT complex. The results suggested that NGR1 can strengthen the affinity stabilization of mTOR and AKT. Our study first revealed that NGR1 enhanced the affinity stabilization of mTOR and AKT, thus promoting the activation of the AKT/mTOR pathway and improving lipid metabolic abnormity in myocardial ischemic rats.

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Section: Resultsmentioning

confidence: 99%

Notoginsenoside R1 Regulates Ischemic Myocardial Lipid Metabolism by Activating the AKT/mTOR Signaling Pathway

Wei

Yan

et al. 2022

Front. Pharmacol.

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“…Previous studies have shown that long-term treatment with PUFAs provides cardioprotection in rats in vivo [ 32 ]. While CD36-mediated transport is pivotal for FA oxidation to support myocardial contractile function [ 33 ], lipotoxicity, in turn, is a well-known paradigm based on cardiac imbalance between reduced utilization of FAs and noninterrupted FA delivery [ 34 ]. Thus, ongoing CPT I-dependent metabolism of FAs and subsequent accumulation of saturated LCAC is known to impair mitochondrial functionality, which further damages the myocardium after I/R [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Fatty Acid Metabolism Increases EPA and DHA Levels and Protects against Myocardial Ischaemia‐Reperfusion Injury in Zucker Rats

Kuka

Makrecka-Kūka

Vilks

et al. 2021

Oxidative Medicine and Cellular Longevity

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Long-chain ω-3 polyunsaturated fatty acids (PUFAs) are known to induce cardiometabolic benefits, but the metabolic pathways of their biosynthesis ensuring sufficient bioavailability require further investigation. Here, we show that a pharmacological decrease in overall fatty acid utilization promotes an increase in the levels of PUFAs and attenuates cardiometabolic disturbances in a Zucker rat metabolic syndrome model. Metabolome analysis showed that inhibition of fatty acid utilization by methyl-GBB increased the concentration of PUFAs but not the total fatty acid levels in plasma. Insulin sensitivity was improved, and the plasma insulin concentration was decreased. Overall, pharmacological modulation of fatty acid handling preserved cardiac glucose and pyruvate oxidation, protected mitochondrial functionality by decreasing long-chain acylcarnitine levels, and decreased myocardial infarct size twofold. Our work shows that partial pharmacological inhibition of fatty acid oxidation is a novel approach to selectively increase the levels of PUFAs and modulate lipid handling to prevent cardiometabolic disturbances.

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“…The genes in relation to Covid-19 which are different are obtained from National Center for Biotechnology Information (NCBI) ( https://www.ncbi.nlm.nih.gov ), Online Mendelian Inheritance in Man(OMIM) ( https://www.omim.org ), GeneCards ( https://www.genecards.org ), and Kyoto Encyclopedia of Genes and Genomes(KEGG) ( https://www.genome.jp/kegg ) [ 37 , 38 ] ( Figure 2 ).…”

Section: Methodsmentioning

confidence: 99%

Reveal the Mechanisms of Yi-Fei-Jian-Pi-Tang on Covid-19 through Network Pharmacology Approach

Lang

Yang

Cai

et al. 2022

Computational Intelligence and Neuroscience

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Objectives. The Traditional Chinese Medicine (TCM) formula Yi-Fei-Jian-Pi-Tang (YFJPT) has been demonstrated effective against Corona Virus Disease 2019 (Covid-19). The aim of this article is to make a thorough inquiry about its active constituent as well as mechanisms against Covid-19 via TCM network pharmacology. Methods. All the ingredients of YFJPT are obtained from the pharmacology database of the TCM system. The genes which are associated with the targets are obtained by utilizing UniProt. The herb-target network is built up by utilizing Cytoscape. The target protein-protein interaction network is built by utilizing the STRING database and Cytoscape. The critical targets of YFJPT are explored by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results. The outcomes show that YFJPT might has 33 therapeutic targets on Covid-19, namely, interleukin 2 (IL2), heme oxygenase 1 (HMOX1), interleukin 4 (IL4), interferon gamma (FNG), α nuclear factor of kappa light polypeptide gene enhancer in Bcells inhibitor, alpha (NFKBIA), nuclear factor-k-gene binding (NFKB), nitric oxide synthase 3 (NOS3), intercellular adhesion molecule 1 (ICAM1), hypoxia inducible factor 1 subunit alpha (HIF1A), mitogen-activated protein kinase 3 (MAPK3), epidermal growth factor receptor (EGFR), interleukin 10 (IL10), jun proto-oncogene (JUN), C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 8 (CXCL8), tumor protein p53 (TP53), interleukin 1 beta (IL1B), AKT serine/threonine kinase 1 (AKT1), tumor necrosis factor (TNF), interleukin 6 (IL6), erb-b2 receptor tyrosine kinase 2 (ERBB2), RELA proto-oncogene (RELA), NF-κB subunit, caspase 8 (CASP8), peroxisome proliferator activated receptor alpha (PPARA), TIMP metallopeptidase inhibitor 1 (TIMP1), transforming growth factor beta 1 (TGFB1), interleukin 1 alpha (IL1A), signal transducer and activator of transcription 1 (STAT1), mitogen-activated protein kinase 8 (MAPK8), myeloperoxidase (MPO), matrix metallopeptidase 3 (MMP3), matrix metallopeptidase 1 (MMP1), and NFE2 like bZIP transcription factor 2 (NFE2L2). The gene enrichment analysis prompts that YFJPT most likely contributes to patients related to Covid-19 by regulating the pathways of cancers. Conclusions. That will lay a foundation for the clinical rational application and further experimental research of YFJPT.

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CD36 as a target for metabolic modulation therapy in cardiac disease

Cited by 24 publications

References 60 publications

Notoginsenoside R1 Regulates Ischemic Myocardial Lipid Metabolism by Activating the AKT/mTOR Signaling Pathway

Notoginsenoside R1 Regulates Ischemic Myocardial Lipid Metabolism by Activating the AKT/mTOR Signaling Pathway

Inhibition of Fatty Acid Metabolism Increases EPA and DHA Levels and Protects against Myocardial Ischaemia‐Reperfusion Injury in Zucker Rats

Reveal the Mechanisms of Yi-Fei-Jian-Pi-Tang on Covid-19 through Network Pharmacology Approach

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