Photobiomodulation Regulation as One Promising Therapeutic Approach for Myocardial Infarction

Myocardial infarction refers to myocardial necrosis caused by acute or persistent coronary ischemia and hypoxia. It is considered to be one of the significant crises threatening human health in the world. Following myocardial infarction, collagen gradually replaces the original tissue due to the loss of many cardiomyocytes, myocardial contractile function decreases, and myocardial fibrosis eventually leads to heart failure. Phototherapy is a new treatment which has shown superior efficacy on the nerve, skeletal muscle, skin, and other tissues. Likewise, there is growing evidence that phototherapy also has many positive effects on the heart. Therefore, this article introduces the progress of research on phototherapy as a new therapeutic strategy in the treatment of myocardial infarction. The wavelength of photobiomodulation in the treatment of myocardial infarction is specific, and the influence of light source power and light duration on the tissue presents a bell-shaped distribution. Under these conditions, phototherapy can promote ATP synthesis and angiogenesis, inhibit the inflammatory response, improve heart function, reduce infarct size, and protect myocardium. In addition, we summarized the molecular mechanisms of phototherapy. According to the location of photoreceptors, they can be divided into mitochondrial and nonmitochondrial parts.

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

Cell Transplantation ◽

10.1177/0963689718786882 ◽

2018 ◽

Vol 27 (8) ◽

pp. 1256-1268 ◽

Cited By ~ 1

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.

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Erratum: Bone Marrow Mesenchymal Stem Cells (BM-MSCs) Improve Heart Function in Swine Myocardial Infarction Model through Paracrine Effects

Scientific Reports ◽

10.1038/srep31528 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 9

Author(s):

Min Cai ◽

Rui Shen ◽

Lei Song ◽

Minjie Lu ◽

Jianguang Wang ◽

...

Keyword(s):

Myocardial Infarction ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Heart Function ◽

Paracrine Effects ◽

Marrow Mesenchymal Stem Cells ◽

Improve Heart Function

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Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction

Journal of Experimental Medicine ◽

10.1084/jem.20160081 ◽

2016 ◽

Vol 213 (7) ◽

pp. 1353-1374 ◽

Cited By ~ 53

Author(s):

Anta Ngkelo ◽

Adèle Richart ◽

Jonathan A. Kirk ◽

Philippe Bonnin ◽

Jose Vilar ◽

...

Keyword(s):

Myocardial Infarction ◽

Mast Cells ◽

Cardiac Function ◽

Cardiac Remodeling ◽

Molecular Mechanisms ◽

Troponin I ◽

Heart Function ◽

Ischemic Disease ◽

Cardiomyocyte Contractility ◽

The Impact

Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit–independent MC-deficient (Cpa3Cre/+) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca2+ desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC-specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA-regulated force–Ca2+ interactions in response to MI. Identification of this MC-cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators.

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Myocardial-restricted ablation of the GTPase RAD results in a pro-adaptive heart response in mice

Journal of Biological Chemistry ◽

10.1074/jbc.ra119.008782 ◽

2019 ◽

Vol 294 (28) ◽

pp. 10913-10927 ◽

Cited By ~ 2

Author(s):

Brooke M. Ahern ◽

Bryana M. Levitan ◽

Sudhakar Veeranki ◽

Mihir Shah ◽

Nemat Ali ◽

...

Keyword(s):

Adrenergic Receptor ◽

Contractile Function ◽

Heart Function ◽

Unmet Need ◽

Calcium Transient ◽

Adverse Outcomes ◽

Endoplasmic Reticulum Calcium ◽

Functional Remodeling ◽

Improve Heart Function ◽

Sustained Increase

Existing therapies to improve heart function target β-adrenergic receptor (β-AR) signaling and Ca2+ handling and often lead to adverse outcomes. This underscores an unmet need for positive inotropes that improve heart function without any adverse effects. The GTPase Ras associated with diabetes (RAD) regulates L-type Ca2+ channel (LTCC) current (ICa,L). Global RAD-knockout mice (gRAD−/−) have elevated Ca2+ handling and increased cardiac hypertrophy, but RAD is expressed also in noncardiac tissues, suggesting the possibility that pathological remodeling is due also to noncardiac effects. Here, we engineered a myocardial-restricted inducible RAD-knockout mouse (RADΔ/Δ). Using an array of methods and techniques, including single-cell electrophysiological and calcium transient recordings, echocardiography, and radiotelemetry monitoring, we found that RAD deficiency results in a sustained increase of inotropy without structural or functional remodeling of the heart. ICa,L was significantly increased, with RAD loss conferring a β-AR–modulated phenotype on basal ICa,L. Cardiomyocytes from RADΔ/Δ hearts exhibited enhanced cytosolic Ca2+ handling, increased contractile function, elevated sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, and faster lusitropy. These results argue that myocardial RAD ablation promotes a beneficial elevation in Ca2+ dynamics, which would obviate a need for increased β-AR signaling to improve cardiac function.

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Mitochondrial Oxidation of the Cytoplasmic Reducing Equivalents at the Onset of Oxidant Stress in the Isoproterenol-Induced Rat Myocardial Infarction

Antioxidants ◽

10.3390/antiox10091444 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1444

Author(s):

Olivia Vázquez-Martínez ◽

Mauricio Díaz-Muñoz ◽

Fernando López-Barrera ◽

Rolando Hernández-Muñoz

Keyword(s):

Myocardial Infarction ◽

Oxidant Stress ◽

Myocardial Necrosis ◽

Atp Synthesis ◽

Mitochondrial Activity ◽

Cardiac Damage ◽

Relevant Role ◽

Functional Consequences ◽

Malate Aspartate Shuttle ◽

Reducing Equivalents

We have developed and characterized a model of isoproterenol (ISO)-induced myocardial necrosis, identifying three stages of cardiac damage: a pre-infarction (0–12 h), infarction (24 h), and post-infarction period (48–96 h). Using this model, we have previously found alterations in calcium homeostasis and their relationship with oxidant stress in mitochondria, which showed deficient oxygen consumption and coupled ATP synthesis. Therefore, the present study was aimed at assessing the mitochondrial ability to transport and oxidize cytoplasmic reducing equivalents (NADH), correlating the kinetic parameters of the malate-aspartate shuttle, oxidant stress, and mitochondrial functionality. Our results showed only discreet effects during the cardiotoxic ISO action on the endogenous malate-aspartate shuttle activity, suggesting that endogenous mitochondrial NADH oxidation capacity (Nohl dehydrogenase) was not affected by the cellular stress. On the contrary, the reconstituted system showed significant enhancement in maximal capacity of the malate-aspartate shuttle activity only at later times (post-infarction period), probably as a compensatory part of cardiomyocytes’ response to the metabolic and functional consequences of the infarcted tissue. Therefore, these findings support the notion that heart damage associated with myocardial infarction suffers a set of sequential biochemical and metabolic modifications within cardiomyocytes, where mitochondrial activity, controlling the redox state, could play a relevant role.

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PEMANFAATAN SEL PUNCA PADA INFARK MIOKARD

JURNAL BIOMEDIK (JBM) ◽

10.35790/jbm.3.1.2011.854 ◽

2013 ◽

Vol 3 (1) ◽

Author(s):

Loretta C. Wangko ◽

J. H. Awaloei ◽

Janry A. Pangemanan

Keyword(s):

Myocardial Infarction ◽

Stem Cells ◽

Stem Cell ◽

Growth Factors ◽

Tissue Repair ◽

Heart Function ◽

Improve Heart Function ◽

Β Blockers ◽

Causes Of Deaths ◽

Myocardial Thickness

Abstract: World-wide, myocardial infarction and heart failure are still the leading causes of deaths and use up a great deal of money. In myocardial infarction there frequently incur cardiomyocyte injuries. Naturally, resident cardiomyocytes will undergo proliferation and contribute to the increasing and repairing of myocardium post infarction. Unfortunately, this capacity of regeneration is very limited. Moreover, injured cardiomyocytes are replaced by scar tissues. Pharmacotherapy with ACE-Inhibitors and β blockers can give some clinical improvement, but can not inhibit the loss of cardiomyocytes. Nowadays, stem cell therapy has proclaimed some promising benefits. Among all the introduced stem cells, mesenchymal stem cells are the most popular since they have the capability to differentiate and then to develop into cardiomyocytes, maintain the myocardial thickness, reduce heart remodeling of the non infarct myocardium, improve heart function, and can be used from allogenic donors. Besides that, these cells are easier to obtain and isolate, are genetically stable, have the capacity for angiogenesis, homing to the injured areas or inflammation, and supplying growth factors and cytokines for tissue repair. Key words: stem cell, cardiomyocyte, transplantation, donor. Abstrak: Infark miokard dan gagal jantung masih merupakan penyebab kematian utama di dunia dan menyerap biaya pengobatan yang tinggi. Pada infark miokard sering terjadi cedera kardiomiosit. Secara alamiah kardiomiosit residen akan mengalami proliferasi dan mengambil bagian dalam meningkatkan dan memulihkan miokard pasca infark. Kapasitas regenerasi ini sangat terbatas. Selain itu kardiomiosit yang cedera akan digantikan oleh jaringan ikat. Farmakoterapi dengan penghambat ACE dan β bloker dapat memberikan perbaikan klinis, tetapi tidak dapat menghambat kehilangan kardiomiosit. Dewasa ini terapi sel punca telah mengumandangkan manfaat yang menjanjikan. Dari berbagai sel punca yang dikemukakan, sel punca mesensimal yang paling diminati oleh karena kemampuannya berdiferensiasi dan berkembang menjadi kardiomiosit, mempertahankan ketebalan miokard, menurunkan remodeling jantung pada bagian yang tidak infark, memperbaiki fungsi jantung. dan dapat diambil dari donor alogenik. Disamping itu, sel-sel ini lebih mudah diperoleh dan diisolasi, stabil secara genetik, berkapasitas angiogenesis, homing ke tempat cedera atau inflamasi, dan memasok growth factors dan sitokin untuk perbaikan jaringan. Kata kunci: sel punca, kardiomiosit, transplantasi, donor.

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Induced pluripotent stem cell (iPSC)-derived cardiomyocytes engraft and improve heart function in a mouse model of acute myocardial infarction

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0031-1297673 ◽

2012 ◽

Vol 60 (S 01) ◽

Cited By ~ 3

Author(s):

A Martens ◽

G Kensah ◽

S Rojas ◽

A Rotärmel ◽

H Baraki ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Stem Cell ◽

Mouse Model ◽

Pluripotent Stem Cell ◽

Heart Function ◽

Induced Pluripotent Stem Cell ◽

Improve Heart Function ◽

Induced Pluripotent

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Abstract 042: Radiation-Associated Cardiovascular Risks for Future Deep-Space Missions

Circulation Research ◽

10.1161/res.113.suppl_1.a042 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Xinhua Yan ◽

Sharath P Sasi ◽

Hannah Gee ◽

Juyong Lee ◽

Yongyao Yang ◽

...

Keyword(s):

Molecular Mechanisms ◽

Low Dose ◽

Diastolic Pressure ◽

Contractile Function ◽

Heart Function ◽

Left Ventricular ◽

Calcium Handling ◽

Cardiovascular Risks ◽

Compensatory Mechanisms ◽

Negative Effect

During the future Moon and Mars missions astronauts will be exposed to space radiation (IR) for extended time. The effect of cosmic IR during and after space flights on cardiovascular (CV) system is unknown. Nine-month old C57BL/6N male mice were IR once with proton 50 cGy or 56Fe 15 cGy, both at 1 GeV/nucleon. We evaluated IR-induced biological responses - underlying molecular mechanisms, calcium handling, signal transduction and gene expression. Cardiac function was assessed by echocardiography and hemodynamic measurements. Left ventricular end diastolic pressure (LVEDP) was increased in 56Fe mice 1 and 3 months post-IR (p<0.001). One month post-IR, compared to control, proton- and 56Fe-IR sarcolemmal Na+-Ca2+ exchanger (NCX) (p<0.007) and sarco(endo)plasmic reticulum calcium-ATPase (SERCA2a, p<0.02) were both increased more than 200% and p-p38 was decreased 400% (p<0.05), suggesting activation of compensatory mechanisms in [Ca2+]i handling in these hearts. By 3 months, compared to control, proton- and 56Fe-IR hearts SERCA2a and p-Creb1 was decreased 200-500% (p<0.02), suggesting reduced capacity in intracellular [Ca2+]i handling, suggesting that [Ca2+]i handling dysfunction combined with LVEDP increase in 56Fe-IR may be due to prolonged activation of compensatory mechanisms that lead to changes in SERCA2a and p-Creb1 levels. By 10 months, compared to control, LVESP was decreased in proton- and 56Fe-IR (p<0.03), suggesting IR-associated decrease in contractile function. However, compared to age-matched controls (18 months), the LVEDP was increased (p<0.05) and dP/dt Min was decreased (p<0.02) in proton-IR but not 56Fe-IR mice. This data suggests that after 10 months proton- but not 56Fe-IR affects considerably contractile and relaxation functions during aging. Our longitudinal 1, 3 and 10 months studies reveal that a single full body low dose proton- and 56Fe-IR have long-lasting negative effect on heart homeostasis during aging. The divergent effects of low dose proton vs. 56Fe-IR on heart function during aging suggest significantly different biological mechanisms responsible for this ion-dependent dichotomy over 10 months post-IR and necessitate further studies into underlying molecular mechanisms.

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