Light Emitting Diode Therapy Protects against Myocardial Ischemia/Reperfusion Injury through Mitigating Neuroinflammation

Background. Neuroinflammation plays a key role in myocardial ischemia-reperfusion (I/R) injury. Previous studies showed that light-emitting diode (LED) therapy might improve M2 microglia activation and brain-derived neurotrophic factor (BDNF) expression, thereby exerting anti-inflammatory effects. Therefore, we hypothesized that LED therapy might reduce myocardial I/R injury by neuroinflammation modulation. Objective. To explore the effect of LED therapy on myocardial I/R-induced injury and seek the underlying mechanism. Methods. Thirty rats were randomly divided into three groups: Control group (without LED treatment or myocardial I/R, n=6), I/R group (with myocardial I/R only, n=12), and LED+I/R group (with myocardial I/R and LED therapy, n=12). Electrocardiogram was recorded continuously during the procedure. In addition, brain tissue was extracted for BDNF, Iba1, and CD206 analyses, and heart tissue for myocardial injury (ischemic size and infarct size), IL-4 and IL-10 mRNA analysis. Results. In comparison with the I/R group, the ischemia size and the infarct size were significantly attenuated by LED therapy in the LED+I/R group. Meanwhile, the microglia activation induced by I/R injury was prominently attenuated by LED treatment either. And it is apparent that there was also an increase in the beneficial neuroinflammation markers (BDNF and CD206) in the paraventricular nucleus (PVN) in the LED+I/R group. Furthermore, the anti-inflammatory cytokines, IL-4 and IL-10, were greatly decreased by I/R while improved by LED treatment in myocardium. Conclusion. LED therapy might reduce neuroinflammation in PVN and decrease myocardium injury by elevating BDNF and M2 microglia.

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Berberine Attenuates Myocardial Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Inflammation Response: Role of Silent Information Regulator 1

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/1689602 ◽

2016 ◽

Vol 2016 ◽

pp. 1-16 ◽

Cited By ~ 37

Author(s):

Liming Yu ◽

Qing Li ◽

Bo Yu ◽

Yang Yang ◽

Zhenxiao Jin ◽

...

Keyword(s):

Myocardial Ischemia ◽

Cardiac Function ◽

Infarct Size ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Inflammation Response ◽

Silent Information Regulator 1 ◽

Anti Inflammatory ◽

Myocardial Ischemia Reperfusion

Berberine (BBR) exerts potential protective effect against myocardial ischemia/reperfusion (MI/R) injury. Activation of silent information regulator 1 (SIRT1) signaling attenuates MI/R injury by reducing oxidative damage and inflammation response. This study investigated the antioxidative and anti-inflammatory effects of BBR treatment in MI/R condition and elucidated its potential mechanisms. Sprague-Dawley rats were treated with BBR in the absence or presence of the SIRT1 inhibitor sirtinol (Stnl) and then subjected to MI/R injury. BBR conferred cardioprotective effects by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase levels, upregulating SIRT1, Bcl-2 expressions, and downregulating Bax and caspase-3 expressions. Stnl attenuated these effects by inhibiting SIRT1 signaling. BBR treatment also reduced myocardium superoxide generation, gp91phoxexpression, malondialdehyde (MDA) level, and cardiac inflammatory markers and increased myocardium superoxide dismutase (SOD) level. However, these effects were also inhibited by Stnl. Consistently, BBR conferred similar antioxidative and anti-inflammatory effects against simulated ischemia reperfusion injury in cultured H9C2 cardiomyocytes. SIRT1 siRNA administration also abolished these effects. In summary, our results demonstrate that BBR significantly improves post-MI/R cardiac function recovery and reduces infarct size against MI/R injury possibly due to its strong antioxidative and anti-inflammatory activity. Additionally, SIRT1 signaling plays a key role in this process.

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Suppression of Long Non-Coding RNA LINC00652 Restores Sevoflurane-Induced Cardioprotection Against Myocardial Ischemia-Reperfusion Injury by Targeting GLP-1R Through the cAMP/PKA Pathway in Mice

Cellular Physiology and Biochemistry ◽

10.1159/000493450 ◽

2018 ◽

Vol 49 (4) ◽

pp. 1476-1491 ◽

Cited By ~ 9

Author(s):

Shu-Bo Zhang ◽

Tie-Jun Liu ◽

Guo-Hua Pu ◽

Bao-Yong Li ◽

Xiao-Zeng Gao ◽

...

Keyword(s):

Myocardial Ischemia ◽

Cardiac Function ◽

Infarct Size ◽

Ischemia Reperfusion ◽

Myocardial Cells ◽

Non Coding Rna ◽

Tnf Α ◽

Myocardial Ischemia Reperfusion ◽

Pka Pathway ◽

Long Non Coding Rna

Background/Aims: Long non-coding RNA (lncRNA) and glucagon-like peptide 1 receptor (GLP-1R) are crucial for heart development and for adult heart structural maintenance and function. Herein, we performed a study to explore the effect of lncRNA LINC00652 (LINC00652) on myocardial ischemia-reperfusion (I/R) injury by targeting GLP-1R through the cyclic adenosine monophosphate-protein kinase A (cAMP/PKA) pathway. Methods: Bioinformatics software was used to screen the long-chain non-coding RNAs associated with myocardial ischemia-reperfusion and to predict target genes. The mRNA and protein levels of LINC00652, GLP-1R and CREB were detected by RT-qPCR and western blotting. In order to identify the interaction between LINC00652 and myocardial I/R injury, the cardiac function, the hemodynamic changes, the pathological changes of the myocardial tissues, the myocardial infarct size, and the apoptosis of myocardial cells of mice were measured. Meanwhile, the levels of serum IL-1β and TNF-α were detected. Results: LINC00652 was overexpressed in the myocardial cells of mice with myocardial I/R injury. GLP-1R is the target gene of LINC00652. We also determined higher levels of LINC00652 and GLP-1R in the I/R modeled mice. Additionally, si-LINC00652 decreased cardiac pathology, infarct size, apoptosis rates of myocardial cells, and levels of IL-1β and TNF-α, and increased GLP-1R expression cardiac function, normal hemodynamic index, and the expression and phosphorylation of GLP-1R and CREB proteins. Conclusion: Taken together, our key findings of the present highlight LINC00652 inhibits the activation of the cAMP/PKA pathway by targeting GLP-1R to reduce the protective effect of sevoflurane on myocardial I/R injury in mice.

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Abstract 16598: The Role of Paraoxonase 2 in Myocardial Ischemia/Reperfusion Injury

Circulation ◽

10.1161/circ.132.suppl_3.16598 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Jingyuan Li ◽

Victor R Grijalva ◽

Srinivasa T Reddy ◽

Mansoureh Eghbali

Keyword(s):

Myocardial Ischemia ◽

Infarct Size ◽

Er Stress ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Ros Production ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

Objectives: Paraoxonases (PON) gene family consists of three proteins PON1, PON2, and PON3. PON2 is an intracellular membrane-associated protein that is widely expressed in vascular cells and many tissues. At the subcellular level, PON2 is localized to both the ER and mitochondria, and protects against oxidative stress. Hypothesis: The aim of this study was to investigate the role of PON2 in myocardial ischemia reperfusion injury. Methods: PON2 deficient (PON2-/-) and WT male mice were subjected to in-vivo ischemia/reperfusion injury. The left anterior descending coronary artery was occluded for 30 min followed by 24 hr of reperfusion. The infarct size, mitochondrial calcium retention capacity (CRC) and reactive oxygen species (ROS) generation were measured. The expression of C/EBP homologous protein (CHOP), GSK3b and phosphate GSK3b protein were examined by Western Blot. The number of animals was 5-7/group and data were expressed as mean±SEM. T test were used for statistical analysis. Probability values <0.05 were considered statistically significant. Results: The infarct size was ~2 fold larger in PON2 deficient mice compared to WT mice (p<0.05). The threshold for opening of mitochondrial permeability transition pore (mPTP) in response to calcium overload was much lower in PON2-/- mice compared with WT mice (173±19 in PON2-/-, 250±41 in WT, nmol/mg-mitochondrial protein, p<0.05). The ROS production was ~2 fold higher in isolated cardiac mitochondria from PON2-/- mice compared with WT mice (p<0.05). ER stress protein CHOP increased significantly in PON2-/- mice compared to WT mice (normalized to WT: 1±0.05 in WT, 1.66±0.08 in PON2-/-, p<0.001). Phospho-GSK3b level was significantly downregulated in in PON2-/- mice compared to WT mice (pGSK3b/GSK3b normalized to WT: 1±0.06 in WT 0.67±0.08 in PON2-/-, p<0.05). Conclusions: PON2 regulates myocardial ischemia/reperfusion injury via inhibiting the opening of mPTP, which is associated with reduced mitochondria ROS production, deactivation of ER stress signaling CHOP and GSK3b.

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Effect of Ranolazine on Infarct Size in a Canine Model of Regional Myocardial Ischemia/Reperfusion

Journal of Cardiovascular Pharmacology ◽

10.1097/00005344-199424060-00009 ◽

1994 ◽

Vol 24 (6) ◽

pp. 921-928 ◽

Cited By ~ 23

Author(s):

Shawn C. Black ◽

Michael R. Gralinski ◽

James G. McCormack ◽

Edward M. Driscoll ◽

Benedict R. Lucchesi

Keyword(s):

Myocardial Ischemia ◽

Infarct Size ◽

Ischemia Reperfusion ◽

Canine Model ◽

Regional Myocardial Ischemia ◽

Myocardial Ischemia Reperfusion

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Repeated intermittent stress exacerbates myocardial ischemia-reperfusion injury

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.274.2.r470 ◽

1998 ◽

Vol 274 (2) ◽

pp. R470-R475 ◽

Cited By ~ 1

Author(s):

Deborah A. Scheuer ◽

Steven W. Mifflin

Keyword(s):

Heart Disease ◽

Myocardial Ischemia ◽

Ischemic Heart Disease ◽

Infarct Size ◽

Chronic Stress ◽

Restraint Stress ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

Chronic stress in humans has been correlated with increased risk for ischemic heart disease. Thus experiments were conducted to determine if repeated intermittent restraint stress increased infarct size in a rat model of myocardial ischemia-reperfusion injury. Male Sprague-Dawley rats were subjected to no stress (control) or to daily restraint stress for 1–1.5 h for 8–14 days (stress protocol A) or for 2 h daily for 11 or 12 days (stress protocol B). Myocardial ischemia-reperfusion (30-min ischemia, 3-h reperfusion) was performed in anesthetized rats. Average baseline arterial pressures were 111 ± 4, 120 ± 10, and 125 ± 7 mmHg in the control, stress protocol A, and stress protocol B groups, respectively. Infarct size (%area at risk) was significantly larger in both groups of stressed rats compared with control rats (58 ± 5, 78 ± 2, and 79 ± 3% in the control, stress protocol A, and stress protocol B groups, respectively). During ischemia or early reperfusion, zero of eight control, two of six protocol A stress, and two of five protocol B stress rats had at least one period of severe arrhythmia. Therefore, these results provide experimental evidence corroborating correlative studies in humans that link chronic stress with increased morbidity and mortality from ischemic heart disease.

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Nrf2 Deficiency Unmasks the Significance of Nitric Oxide Synthase Activity for Cardioprotection

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/8309698 ◽

2018 ◽

Vol 2018 ◽

pp. 1-15 ◽

Cited By ~ 9

Author(s):

Ralf Erkens ◽

Tatsiana Suvorava ◽

Thomas R. Sutton ◽

Bernadette O. Fernandez ◽

Monika Mikus-Lelinska ◽

...

Keyword(s):

Myocardial Ischemia ◽

Infarct Size ◽

De Novo ◽

Ischemia Reperfusion Injury ◽

Systolic Function ◽

Ischemia Reperfusion ◽

Systolic Dysfunction ◽

Left Ventricular ◽

Early Reperfusion ◽

Myocardial Ischemia Reperfusion

The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key master switch that controls the expression of antioxidant and cytoprotective enzymes, including enzymes catalyzing glutathione de novo synthesis. In this study, we aimed to analyze whether Nrf2 deficiency influences antioxidative capacity, redox state, NO metabolites, and outcome of myocardial ischemia reperfusion (I/R) injury. In Nrf2 knockout (Nrf2 KO) mice, we found elevated eNOS expression and preserved NO metabolite concentrations in the aorta and heart as compared to wild types (WT). Unexpectedly, Nrf2 KO mice have a smaller infarct size following myocardial ischemia/reperfusion injury than WT mice and show fully preserved left ventricular systolic function. Inhibition of NO synthesis at onset of ischemia and during early reperfusion increased myocardial damage and systolic dysfunction in Nrf2 KO mice, but not in WT mice. Consistent with this, infarct size and diastolic function were unaffected in eNOS knockout (eNOS KO) mice after ischemia/reperfusion. Taken together, these data suggest that eNOS upregulation under conditions of decreased antioxidant capacity might play an important role in cardioprotection against I/R. Due to the redundancy in cytoprotective mechanisms, this fundamental antioxidant property of eNOS is not evident upon acute NOS inhibition in WT mice or in eNOS KO mice until Nrf2-related signaling is abrogated.

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