scholarly journals Acetyl-CoA production by specific metabolites promotes cardiac repair after myocardial infarction via histone acetylation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ienglam Lei ◽  
Shuo Tian ◽  
Wenbin Gao ◽  
Liu Liu ◽  
Yijing Guo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Histone Acetylation ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Carbon Sources ◽  
Metabolic Enzyme ◽  
Acetyl Coa ◽  
Antioxidant Genes ◽  
Heart Repair ◽  
Energy Deprivation

Myocardial infarction (MI) is accompanied by severe energy deprivation and extensive epigenetic changes. However, how energy metabolism and chromatin modifications are interlinked during MI and heart repair has been poorly explored. Here, we examined the effect of different carbon sources that are involved in the major metabolic pathways of acetyl-CoA synthesis on myocardial infarction and found that elevation of acetyl-CoA by sodium octanoate (8C) significantly improved heart function in ischemia reperfusion (I/R) rats. Mechanistically, 8C reduced I/R injury by promoting histone acetylation which in turn activated the expression of antioxidant genes and inhibited cardiomyocyte (CM) apoptosis. Furthermore, we elucidated that 8C-promoted histone acetylation and heart repair were carried out by metabolic enzyme medium-chain acyl-CoA dehydrogenase (MCAD) and histone acetyltransferase Kat2a, suggesting that 8C dramatically improves cardiac function mainly through metabolic acetyl-CoA-mediated histone acetylation. Therefore, our study uncovers an interlinked metabolic/epigenetic network comprising 8C, acetyl-CoA, MCAD, and Kat2a to combat heart injury.

scholarly journals Acetyl-CoA production by select metabolic pathways promotes cardiac repair after myocardial infarction via mediating histone acetylation

2019 ◽  
Author(s):  
Ienglam Lei ◽  
Shuo Tian ◽  
Wenbin Gao ◽  
Liu Liu ◽  
Yijing Guo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Histone Acetylation ◽  
Metabolic Pathways ◽  
Heart Function ◽  
Carbon Sources ◽  
Metabolic Enzyme ◽  
Acetyl Coa ◽  
Antioxidant Genes ◽  
Heart Repair ◽  
Energy Deprivation

AbstractMyocardial infarction (MI) is accompanied by severe energy deprivation and extensive epigenetic changes. However, how energy metabolism and chromatin modifications are interlinked during MI and heart repair has been poorly explored. Here, we examined the effect of different carbon sources that involved in the major metabolic pathways of acetyl-CoA synthesis on myocardial infarction and found that elevation of acetyl-CoA significantly improved heart function in I/R rats by administration of sodium octanoate (8C). Mechanistically, 8C prevented I/R injury by promoting histone acetylation which in turn activated the expression of antioxidant genes HO1, NQO1 and SOD2 and inhibited cardiomyocyte apoptosis. Furthermore, we identified that 8C-promoted histone acetylation and heart repair were carried out by metabolic enzyme medium-chain acyl-CoA dehydrogenase (MCAD) and histone acetyltransferase Kat2a. Therefore, our results demonstrate that 8C dramatically improves cardiac function through metabolic acetyl-CoA-mediated histone acetylation. This study uncovers an interlinked metabolic/epigenetic network comprising 8C, acetyl-CoA, MCAD, and Kat2a in stimulating histone acetylation and anti-oxidative stress gene expression to combat heart injury.

scholarly journals Trop2 Guarantees Cardioprotective Effects of Cortical Bone-Derived Stem Cells on Myocardial Ischemia/Reperfusion Injury

2018 ◽  
Vol 27 (8) ◽  
pp. 1256-1268 ◽  
Author(s):  
Tianyu Li ◽  
Yunshu Su ◽  
Xiongli Yu ◽  
Durgahee S.A. Mouniir ◽  
Jackson Ferdinand Masau ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Myocardial Ischemia ◽  
Cortical Bone ◽  
Heart Function ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Promising Therapeutic Approach ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion

Stem cell transplantation represents a promising therapeutic approach for myocardial ischemia/reperfusion (I/R) injury, where cortical bone-derived stem cells (CBSCs) stand out and hold superior cardioprotective effects on myocardial infarction than other types of stem cells. However, the molecular mechanism underlying CBSCs function on myocardial I/R injury is poorly understood. In a previous study, we reported that Trop2 (trophoblast cell-surface antigen 2) is expressed exclusively on the CBSCs membrane, and is involved in regulation of proliferation and differentiation of CBSCs. In this study, we found that the Trop2 is essential for the ameliorative effects of CBSCs on myocardial I/R-induced heart damage via promoting angiogenesis and inhibiting cardiomyocytes apoptosis in a paracrine manner. Trop2 is required for the colonization of CBSCs in recipient hearts. When Trop2 was knocked out, CBSCs largely lost their functions in lowering myocardial infarction size, improving heart function, enhancing capillary density, and suppressing myocardial cell death. Mechanistically, activating the AKT/GSK3β/β-Catenin signaling axis contributes to the essential role of Trop2 in CBSCs-rendered cardioprotective effects on myocardial I/R injury. In conclusion, maintaining the expression and/or activation of Trop2 in CBSCs might be a promising strategy for treating myocardial infarction, I/R injury, and other related heart diseases.

scholarly journals The impact of pressure overload on coronary vascular changes following myocardial infarction in rats

2013 ◽  
Vol 304 (5) ◽  
pp. H719-H728 ◽  
Author(s):  
Jiqiu Chen ◽  
Artiom Petrov ◽  
Elisa Yaniz-Galende ◽  
Lifan Liang ◽  
Hans J. de Haas ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Pulmonary Edema ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Pressure Overload ◽  
Coronary Artery Ligation ◽  
Pathological Changes ◽  
Vascular Changes ◽  
Atrial Thrombus ◽  
The Impact

This study investigates the impact of pressure overload on vascular changes after myocardial infarction (MI) in rats. To evaluate the effect of pressure overload, MI was induced in three groups: 1) left coronary artery ligation for 1 mo (MI-1m), 2) ischemia 30 min/reperfusion for 1 mo (I/R-1m), and 3) ischemia-reperfusion (I/R) was performed after pressure overload induced by aortic banding for 2 mo; 1 mo post-I/R, aortic constriction was released (Ab+I/R+DeAb). Heart function was assessed by echocardiography and in vivo hemodynamics. Resin casting and three-dimensional imaging with microcomputed tomography were used to characterize changes in coronary vasculature. TTC (triphenyltetrazohum chloride) staining and Masson's Trichrome were conducted in parallel experiments. In normal rats, MI induced by I/R and permanent occlusion was transmural or subendocardial. Occluded arterial branches vanished in MI-1m rats. A short residual tail was retained, distal to the occluded site in the ischemic area in I/R-1m hearts. Vascular pathological changes in transmural MI mostly occurred in ischemic areas and remote vasculature remained normal. In pressure overloaded rats, I/R injury induced a sub-MI in which ischemia was transmural, but myocardium in the involved area had survived. The ischemic arterial branches were preserved even though the capillaries were significantly diminished and the pathological changes were extended to remote areas, characterized by fibrosis, atrial thrombus, and pulmonary edema in the Ab+I/R+DeAb group. Pressure overload could increase vascular tolerance to I/R injury, but also trigger severe global ventricular fibrosis and results in atrial thrombus and pulmonary edema.

scholarly journals Innate Lymphoid Cells and Myocardial Infarction

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenling Yang ◽  
Jibin Lin ◽  
Jin Zhou ◽  
Yuqi Zheng ◽  
Shijiu Jiang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
High Morbidity ◽  
Human Immune System ◽  
Treatment And Prevention ◽  
Heart Repair ◽  
Myocardial Ischemia Reperfusion

Myocardial infarction results from obstruction of a coronary artery that causes insufficient blood supply to the myocardium and leads to ischemic necrosis. It is one of the most common diseases threatening human health and is characterized by high morbidity and mortality. Atherosclerosis is the pathological basis of myocardial infarction, and its pathogenesis has not been fully elucidated. Innate lymphoid cells (ILCs) are an important part of the human immune system and participate in many processes, including inflammation, metabolism and tissue remodeling, and play an important role in atherosclerosis. However, their specific roles in myocardial infarction are unclear. This review describes the current understanding of the relationship between innate lymphoid cells and myocardial infarction during the acute phase of myocardial infarction, myocardial ischemia-reperfusion injury, and heart repair and regeneration following myocardial infarction. We suggest that this review may provide new potential intervention targets and ideas for treatment and prevention of myocardial infarction.

scholarly journals The Drosophila Citrate Lyase Is Required for Cell Division during Spermatogenesis

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 206
Author(s):  
Maria Laura Di Giorgio ◽  
Patrizia Morciano ◽  
Elisabetta Bucciarelli ◽  
Antonella Porrazzo ◽  
Francesca Cipressa ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Division ◽  
Histone Acetylation ◽  
Male Meiosis ◽  
Metabolic Enzyme ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Alternative Pathways ◽  
Citrate Lyase ◽  
First Time

The Drosophila melanogaster DmATPCL gene encodes for the human ATP Citrate Lyase (ACL) ortholog, a metabolic enzyme that from citrate generates glucose-derived Acetyl-CoA, which fuels central biochemical reactions such as the synthesis of fatty acids, cholesterol and acetylcholine, and the acetylation of proteins and histones. We had previously reported that, although loss of Drosophila ATPCL reduced levels of Acetyl-CoA, unlike its human counterpart, it does not affect global histone acetylation and gene expression, suggesting that its role in histone acetylation is either partially redundant in Drosophila or compensated by alternative pathways. Here, we describe that depletion of DmATPCL affects spindle organization, cytokinesis, and fusome assembly during male meiosis, revealing an unanticipated role for DmATPCL during spermatogenesis. We also show that DmATPCL mutant meiotic phenotype is in part caused by a reduction of fatty acids, but not of triglycerides or cholesterol, indicating that DmATPCL-derived Acetyl-CoA is predominantly devoted to the biosynthesis of fatty acids during spermatogenesis. Collectively, our results unveil for the first time an involvement for DmATPCL in the regulation of meiotic cell division, which is likely conserved in human cells.

scholarly journals Protective Effects of Polyphenols against Ischemia/Reperfusion Injury

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3469
Author(s):  
Martina Cebova ◽  
Olga Pechanova
Keyword(s):  
Myocardial Infarction ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Radical Scavenging ◽  
Myocardial Necrosis ◽  
Protective Effects ◽  
Natural Polyphenols ◽  
Tissue Degeneration ◽  
Heart Contractility

Myocardial infarction (MI) is a leading cause of morbidity and mortality across the world. It manifests as an imbalance between blood demand and blood delivery in the myocardium, which leads to cardiac ischemia and myocardial necrosis. While it is not easy to identify the first pathogenic cause of MI, the consequences are characterized by ischemia, chronic inflammation, and tissue degeneration. A poor MI prognosis is associated with extensive cardiac remodeling. A loss of viable cardiomyocytes is replaced with fibrosis, which reduces heart contractility and heart function. Recent advances have given rise to the concept of natural polyphenols. These bioactive compounds have been studied for their pharmacological properties and have proven successful in the treatment of cardiovascular diseases. Studies have focused on their various bioactivities, such as their antioxidant and anti-inflammatory effects and free radical scavenging. In this review, we summarized the effects and benefits of polyphenols on the cardiovascular injury, particularly on the treatment of myocardial infarction in animal and human studies.

scholarly journals Non-coding RNAs modulate autophagy in myocardial ischemia-reperfusion injury: a systematic review

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Fuwen Huang ◽  
Jingting Mai ◽  
Jingwei Chen ◽  
Yinying He ◽  
Xiaojun Chen
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Diseases ◽  
Myocardial Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Circular Rnas ◽  
Non Coding Rnas ◽  
Myocardial Ischemia Reperfusion

AbstractThe myocardial infarction is the main cause of morbidity and mortality in cardiovascular diseases around the world. Although the timely and complete reperfusion via Percutaneous Coronary Intervention (PCI) or thrombolysis have distinctly decreased the mortality of myocardial infarction, reperfusion itself may lead to supererogatory irreversible myocardial injury and heart function disorders, namely ischemia-reperfusion (I/R) injury. Extensive studies have indicated that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play important roles in the progress of myocardial I/R injury, which is closely correlative with cardiomyocytes autophagy. Moreover, autophagy plays an important role in maintaining homeostasis and protecting cells in the myocardial ischemia reperfusion and cardiomyocyte hypoxia-reoxygenation (H/R) progress. In this review, we first introduced the biogenesis and functions of ncRNAs, and subsequently summarized the roles and relevant molecular mechanisms of ncRNAs regulating autophagy in myocardial I/R injury. We hope that this review in addition to develop a better understanding of the physiological and pathological roles of ncRNAs, can also lay a foundation for the therapies of myocardial I/R injury, and even for other related cardiovascular diseases.

scholarly journals Phosphatidylserine Supplementation as a Novel Strategy for Reducing Myocardial Infarct Size and Preventing Adverse Left Ventricular Remodeling

2021 ◽  
Vol 22 (9) ◽  
pp. 4401
Author(s):  
David Schumacher ◽  
Adelina Curaj ◽  
Mareike Staudt ◽  
Franziska Cordes ◽  
Andreea R. Dumitraşcu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
Ventricular Remodeling ◽  
Heart Function ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Novel Strategy

Phosphatidylserines are known to sustain skeletal muscle activity during intense activity or hypoxic conditions, as well as preserve neurocognitive function in older patients. Our previous studies pointed out a potential cardioprotective role of phosphatidylserine in heart ischemia. Therefore, we investigated the effects of phosphatidylserine oral supplementation in a mouse model of acute myocardial infarction (AMI). We found out that phosphatidylserine increases, significantly, the cardiomyocyte survival by 50% in an acute model of myocardial ischemia-reperfusion. Similar, phosphatidylserine reduced significantly the infarcted size by 30% and improved heart function by 25% in a chronic model of AMI. The main responsible mechanism seems to be up-regulation of protein kinase C epsilon (PKC-ε), the main player of cardio-protection during pre-conditioning. Interestingly, if the phosphatidylserine supplementation is started before induction of AMI, but not after, it selectively inhibits neutrophil’s activation, such as Interleukin 1 beta (IL-1β) expression, without affecting the healing and fibrosis. Thus, phosphatidylserine supplementation may represent a simple way to activate a pre-conditioning mechanism and may be a promising novel strategy to reduce infarct size following AMI and to prevent myocardial injury during myocardial infarction or cardiac surgery. Due to the minimal adverse effects, further investigation in large animals or in human are soon possible to establish the exact role of phosphatidylserine in cardiac diseases.

scholarly journals Exosomal Expression of CXCR4 Targets Cardioprotective Vesicles to Myocardial Infarction and Improves Outcome after Systemic Administration

2019 ◽  
Vol 20 (3) ◽  
pp. 468 ◽  
Author(s):  
Alessandra Ciullo ◽  
Vanessa Biemmi ◽  
Giuseppina Milano ◽  
Sara Bolis ◽  
Elisabetta Cervio ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Systemic Administration ◽  
Systemic Delivery ◽  
Cxcr4 Antagonist ◽  
Intramyocardial Injection ◽  
Vitro Effect

Cell therapy has been evaluated to enhance heart function after injury. Delivered cells mostly act via paracrine mechanisms, including secreted growth factors, cytokines, and vesicles, such as exosomes (Exo). Intramyocardial injection of cardiac-resident progenitor cells (CPC)-derived Exo reduced scarring and improved cardiac function after myocardial infarction in rats. Here, we explore a clinically relevant approach to enhance the homing process to cardiomyocytes (CM), which is crucial for therapeutic efficacy upon systemic delivery of Exo. By overexpressing exosomal CXCR4, we increased the efficacy of plasmatic injection of cardioprotective Exo-CPC by increasing their bioavailability to ischemic hearts. Intravenous injection of ExoCXCR4 significantly reduced infarct size and improved left ventricle ejection fraction at 4 weeks compared to ExoCTRL (p < 0.01). Hemodynamic measurements showed that ExoCXCR4 improved dp/dt min, as compared to ExoCTRL and PBS group. In vitro, ExoCXCR4 was more bioactive than ExoCTRL in preventing CM death. This in vitro effect was independent from SDF-1α, as shown by using AMD3100 as specific CXCR4 antagonist. We showed, for the first time, that systemic administration of Exo derived from CXCR4-overexpressing CPC improves heart function in a rat model of ischemia reperfusion injury These data represent a substantial step toward clinical application of Exo-based therapeutics in cardiovascular disease.

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