scholarly journals Human Lysyl Oxidase Over-Expression Enhances Baseline Cardiac Oxidative Stress but Does Not Aggravate ROS Generation or Infarct Size Following Myocardial Ischemia-Reperfusion

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 75
Author(s):  
Laura Valls-Lacalle ◽  
Lídia Puertas-Umbert ◽  
Saray Varona ◽  
José Martínez-González ◽  
Cristina Rodríguez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Infarct Size ◽  
Cardiac Remodeling ◽  
Lysyl Oxidase ◽  
Ischemia Reperfusion ◽  
Ros Production ◽  
Over Expression ◽  
Myocardial Oxidative Stress ◽  
Myocardial Ischemia Reperfusion

Lysyl oxidase (LOX) is an enzyme critically involved in collagen maturation, whose activity releases H2O2 as a by-product. Previous studies demonstrated that LOX over-expression enhances reactive oxygen species (ROS) production and exacerbates cardiac remodeling induced by pressure overload. However, whether LOX influences acute myocardial infarction and post-infarct left ventricular remodeling and the contribution of LOX to myocardial oxidative stress following ischemia-reperfusion have not been analyzed. Isolated hearts from transgenic mice over-expressing human LOX in the heart (TgLOX) and wild-type (WT) littermates were subjected to global ischemia and reperfusion. Although under basal conditions LOX transgenesis is associated with higher cardiac superoxide levels than WT mice, no differences in ROS production were detected in ischemic hearts and a comparable acute ischemia-reperfusion injury was observed (infarct size: 56.24 ± 9.44 vs. 48.63 ± 2.99% of cardiac weight in WT and TgLOX, respectively). Further, similar changes in cardiac dimensions and function were observed in TgLOX and WT mice 28 days after myocardial infarction induced by transient left anterior descending (LAD) coronary artery occlusion, and no differences in scar area were detected (20.29 ± 3.10 vs. 21.83 ± 2.83% of left ventricle). Our data evidence that, although LOX transgenesis induces baseline myocardial oxidative stress, neither ROS production, infarct size, nor post-infarction cardiac remodeling were exacerbated following myocardial ischemia-reperfusion.

scholarly journals Cardioprotective Effect of the Aqueous Extract of Lavender Flower against Myocardial Ischemia/Reperfusion Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Dong Wang ◽  
Xin Guo ◽  
Mingjie Zhou ◽  
Jichun Han ◽  
Bo Han ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Aqueous Extract ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Myocardial Oxidative Stress ◽  
Myocardial Ischemia Reperfusion

This study was conducted to evaluate the cardioprotective property of the aqueous extract of lavender flower (LFAE). The myocardial ischemia/reperfusion (I/R) injury of rat was prepared by Langendorff retrograde perfusion technology. The heart was preperfused with K-H solution containing LFAE for 10 min before 20 minutes global ischemia, and then the reperfusion with K-H solution was conducted for 45 min. The left ventricular developed pressure (LVDP) and the maximum up/downrate of left ventricular pressure (±dp/dtmax) were recorded by physiological recorder as the myocardial function and the myocardial infarct size was detected by TTC staining. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities in the effluent were measured to determine the myocardial injury degree. The superoxide anion dismutase (SOD) and malondialdehyde (MDA) in myocardial tissue were detected to determine the oxidative stress degree. The results showed that the pretreatment with LFAE significantly decreased the myocardial infarct size and also decreased the LDH, CK activities, and MDA level, while it increased the LVDP, ±dp/dtmax, SOD activities, and the coronary artery flow. Our findings indicated that LFAE could provide protection for heart against the I/R injury which may be related to the improvement of myocardial oxidative stress states.

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

Circulation ◽  
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.

Cardioprotective Effects of Saponins from Rhizoma Panacis Majoris on Myocardial Ischemia/Reperfusion Injury via Scavenging Excessive Reactive Oxygen Species

2014 ◽  
Vol 934 ◽  
pp. 165-172
Author(s):  
Cai Hong Bai ◽  
Hai Bo He ◽  
Fan Cheng ◽  
Jun Zhi Wang ◽  
Xiao Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Radical Scavenging ◽  
Protective Effects ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion

Saponins from Rhizoma Panacis Majoris (SRPM), the bioactive component inRhizoma Panacis Majoris, were reported to possess protective effects on myocardial injury, but the underlying mechanisms remain poorly understood. This study was performed to investigate the protective effects and possible mechanism of SRPM on myocardial ischemia/reperfusion (I/R) injury in vivo. Cardioprotective effects of SPRM in I/R rats was evaluated by hemodynamic, infarct size, biochemical values, histopathological observations, antioxidative relative gene expressions; And the antioxidant activity of SPRM was studied using DPPH scavenging and β-carotene/linoleic acid tests. In the study, we found that SRPM possessed significant free radical-scavenging activity and considerable antioxidant activity, and significantly improved cardiac function, serum biochemical index and antioxidation level, decreased infarct size, reversed the down-regulated mRNA expressions of the SOD1, SOD2, SOD3 in I/R rats. The studies demonstrated that oxidative stress caused the overgeneration and accumulation of ROS, which was central of myocardial I/R injury. SPRM exerted beneficially cardioprotective effects on myocardial I/R injury, mainly scavenging oxidative stress-triggered overgeneration and accumulation of ROS, alleviating myocardial I/R injury and apoptotic cell death.

scholarly journals AMPK/SIRT1 Pathway is Involved in Arctigenin-Mediated Protective Effects Against Myocardial Ischemia-Reperfusion Injury

2021 ◽  
Vol 11 ◽  
Author(s):  
Cheng-Yin Liu ◽  
Yi Zhou ◽  
Tao Chen ◽  
Jing-Chao Lei ◽  
Xue-Jun Jiang
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Dependent Manner ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Arctigenin, one of the active ingredients extracted from Great Burdock (Arctium lappa) Achene, has been found to relieve myocardial infarction injury. However, the specific mechanism of Arctigenin against myocardial infarction remains largely unknown. Here, both acute myocardial ischemia-reperfusion injury (AMI/R) rat model and oxygen glucose deprivation (OGD)-induced myocardial cell injury model were constructed to explore the underlying role of AMPK/SIRT1 pathway in Arctigenin-mediated effects. The experimental data in our study demonstrated that Arctigenin ameliorated OGD-mediated cardiomyocytes apoptosis, inflammation and oxidative stress in a dose-dependent manner. Besides, Arctigenin activated AMPK/SIRT1 pathway and downregulated NF-κB phosphorylation in OGD-treated cardiomyocytes, while inhibiting AMPK or SIRT1 by the Compound C (an AMPK inhibitor) or SIRT1-IN-1 (a SIRT1 inhibitor) significantly attenuated Arctigenin-exerted protective effects on cardiomyocytes. In the animal experiments, Arctigenin improved the heart functions and decreased infarct size of the AMI/R-rats, accompanied with downregulated oxidative stress, inflammation and apoptotic levels in the heart tissues. What’s more, Arctigenin enhanced the AMPK/SIRT1 pathway and repressed NF-κB pathway activation. Taken together, our data indicated that Arctigenin reduced cardiomyocytes apoptosis against AMI/R-induced oxidative stress and inflammation at least via AMPK/SIRT1 pathway.

scholarly journals Effects on cardiac function, remodeling and inflammation following myocardial ischemia–reperfusion injury or unreperfused myocardial infarction in hypercholesterolemic APOE*3-Leiden mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Niek J. Pluijmert ◽  
Cindy I. Bart ◽  
Wilhelmina H. Bax ◽  
Paul H. A. Quax ◽  
Douwe E. Atsma
Keyword(s):  
Myocardial Infarction ◽  
Clinical Trials ◽  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Apo E ◽  
Lv Remodeling ◽  
Myocardial Ischemia Reperfusion

Abstract Many novel therapies to treat myocardial infarction (MI), yielding promising results in animal models, nowadays failed in clinical trials for several reasons. The most used animal MI model is based on permanent ligation of the left anterior descending (LAD) coronary artery in healthy mice resulting in transmural MI, while in clinical practice reperfusion is usually accomplished by primary percutaneous coronary interventions (PCI) limiting myocardial damage and inducing myocardial ischemia–reperfusion (MI-R) injury. To evaluate a more similar murine MI model we compared MI-R injury to unreperfused MI in hypercholesterolemic apolipoprotein (APO)E*3-Leiden mice regarding effects on cardiac function, left ventricular (LV) remodeling and inflammation. Both MI-R and MI resulted in significant LV dilation and impaired cardiac function after 3 weeks. Although LV dilation, displayed by end-diastolic (EDV) and end-systolic volumes (ESV), and infarct size (IS) were restricted following MI-R compared to MI (respectively by 27.6% for EDV, 39.5% ESV, 36.0% IS), cardiac function was not preserved. LV-wall thinning was limited with non-transmural LV fibrosis in the MI-R group (66.7%). Two days after inducing myocardial ischemia, local leucocyte infiltration in the infarct area was decreased following MI-R compared to MI (36.6%), whereas systemic circulating monocytes were increased in both groups compared to sham (130.0% following MI-R and 120.0% after MI). Both MI-R and MI models against the background of a hypercholesterolemic phenotype appear validated experimental models, however reduced infarct size, restricted LV remodeling as well as a different distributed inflammatory response following MI-R resemble the contemporary clinical outcome regarding primary PCI more accurately which potentially provides better predictive value of experimental therapies in successive clinical trials.

Adrenomedullin gene delivery attenuates myocardial infarction and apoptosis after ischemia and reperfusion

2003 ◽  
Vol 285 (4) ◽  
pp. H1506-H1514 ◽  
Author(s):  
Kazuo Kato ◽  
Hang Yin ◽  
Jun Agata ◽  
Hideaki Yoshida ◽  
Lee Chao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Infarct Size ◽  
P38 Mapk ◽  
Ischemia Reperfusion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Area At Risk ◽  
Calcitonin Gene ◽  
Myocardial Ischemia Reperfusion

Adrenomedullin (AM) has been shown to protect against cardiac remodeling. In this study, we investigated the potential role of AM in myocardial ischemia-reperfusion (I/R) injury through adenovirus-mediated gene delivery. One week after AM gene delivery, rats were subjected to 30-min coronary occlusion, followed by 2-h reperfusion. AM gene transfer significantly reduced the ratio of infarct size to ischemic area at risk and the occurrence of sustained ventricular fibrillation compared with control rats. AM gene delivery also attenuated apoptosis, assessed by both terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and DNA laddering. The effect of AM gene transfer on infarct size, arrhythmia, and apoptosis was abolished by an AM antagonist, calcitonin gene-related peptide [CGRP(8–37)]. Expression of human AM significantly increased cardiac cGMP levels and reduced superoxide production, superoxide density, NAD(P)H oxidase activity, p38 MAPK activation, and Bax levels. Moreover, AM increased Akt and Bad phosphorylation and Bcl-2 levels, but decreased caspase-3 activation. These results indicate that AM protects against myocardial infarction, arrhythmia, and apoptosis in I/R injury via suppression of oxidative stress-induced Bax and p38 MAPK phosphorylation and activation of the Akt-Bad-Bcl-2 signaling pathway. Successful application of this technology may have a protective effect in coronary artery diseases.

scholarly journals ADAMTS13 Deficiency Exacerbates VWF-Dependent Acute Myocardial Ischemia/Reperfusion Injury in Mice

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 264-264 ◽  
Author(s):  
Chintan Gandhi ◽  
David G Motto ◽  
Melissa Jensen ◽  
Steven R. Lentz ◽  
Anil K Chauhan
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neutrophil Infiltration ◽  
Adamts13 Deficiency ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocyte Apoptosis ◽  
Myocardial Ischemia Reperfusion

Abstract Abstract 264 Background and objective: ADAMTS13 (A Disintegrin And Metalloprotease with Thrombospondin type I repeats-13) cleaves von Willebrand factor (VWF), a large multimeric protein that plays an important role in thrombus formation by binding to platelets following vascular injury. Epidemiological studies suggest that elevated VWF levels and reduced ADAMTS13 activity in the plasma are risk factors for myocardial infarction. It remains unknown, however, whether the ADAMTS13-VWF axis plays a causal role in the pathophysiology of myocardial infarction. We tested the hypothesis that ADAMTS13 reduces VWF-mediated acute myocardial ischemia/reperfusion (I/R) injury in mice. Methods: Myocardial infarction was induced in male mice (8–10 weeks of age) by ligating the left anterior descending coronary artery for 30 minutes followed by 23.5 hours of reperfusion. The extent of myocardium damage was evaluated by measuring infarct size (%) in 2 mm serial sections stained with 2% triphenyl-2, 3, 4-tetrazolium-chloride. Neutrophil infiltration and myocyte apoptosis in the left ventricular area was quantified by immunohistochemistry and TUNEL staining respectively. Results: Adamts13 -/- mice exhibited significantly increased infarct size (22.2 % ± 1.1 %, P <.01) compared with WT mice (16.9 % ± 1.2 %, P<0.05). Plasma levels of cardiac troponin T (cTnT), an index of myocyte injury, were significantly higher in Adamts13−/− mice compared with WT mice (P <0.01). Adamts13+/− mice, which have a 50% reduction in ADAMTS13 activity, had similar sized infarcts (16.6 ± 1.3%) and cTnT levels compared to those in WT mice. Larger infarcts in the Adamts13−/− mice were concordant with increased neutrophil infiltration and myocyte apoptosis compared with WT mice. Because VWF remains the only known substrate of ADAMTS13 in multiple experimental models, we hypothesized that ADAMTS13 reduces myocardial injury through its proteolytic effect on hyper adhesive ULVWF and /or VWF. Vwf−/− mice exhibited significantly reduced infarct size, neutrophil infiltration, and myocyte apoptosis compared with WT mice, suggesting a detrimental role for VWF in myocardial I/R injury. VWF-deficient mice have a defect in regulation of endothelial P-selectin due to the loss of Weibel-Palade body formation. To confirm that exacerbated myocardial I/R injury in the setting of ADAMTS13 deficiency is dependent on VWF rather than P-selectin, we compared WT and Adamts13−/− mice treated with anti-VWF inhibitory antibodies. Treating WT or Adamts13−/− mice with neutralizing antibodies to VWF prior to myocardial I/R injury significantly reduced infarct size compared with control Ig-treated mice, suggesting that exacerbated myocardial I/R injury observed in Adamts13−/− mice is entirely VWF-dependent. Finally, myocardial I/R injury in Adamts13−/−/Vwf−/− mice was similar to that in Vwf−/− mice, suggesting that the exacerbated myocardial I/R injury observed in the setting of ADAMTS13 deficiency is VWF-dependent. Conclusion: These findings reveal a new role for anti-thrombotic enzyme ADAMTS13 in reducing VWF-mediated myocardial ischemia/reperfusion injury. Disclosures: Lentz: Novo Nordisk A/S: Consultancy, Investigator Other.

scholarly journals Exercise and Cardioprotection: A Natural Defense Against Lethal Myocardial Ischemia–Reperfusion Injury and Potential Guide to Cardiovascular Prophylaxis

2018 ◽  
Vol 24 (1) ◽  
pp. 18-30 ◽  
Author(s):  
Mohammed Andaleeb Chowdhury ◽  
Haden K. Sholl ◽  
Megan S. Sharrett ◽  
Steven T. Haller ◽  
Christopher C. Cooper ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Beneficial Effects ◽  
Natural Defense ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Similar to ischemic preconditioning, high-intensity exercise has been shown to decrease infarct size following myocardial infarction. In this article, we review the literature on beneficial effects of exercise, exercise requirements for cardioprotection, common methods utilized in laboratories to study this phenomenon, and discuss possible mechanisms for exercise-mediated cardioprotection.

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