scholarly journals MG53 E3 Ligase-dead Mutant Protects Diabetic Hearts from Acute Ischemic/Reperfusion Injury and Ameliorates Diet-induced Cardiometabolic Damage

2021 ◽  
Author(s):  
Han Feng ◽  
Hao Shen ◽  
Matthew J Robeson ◽  
Yue-Han Wu ◽  
Hong-Kun Wu ◽  
...  
Keyword(s):  
Side Effects ◽  
Metabolic Disorders ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Metabolic Stress ◽  
E3 Ligase ◽  
Cardiovascular Complications ◽  
Membrane Repair ◽  
Cardiac Damage ◽  
Metabolic Side Effects

Cardiometabolic diseases, including diabetes and its cardiovascular complications, are the global leading cause of death, highlighting a major unmet medical need. Over the last decade, MG53, also named TRIM72, has emerged as a powerful agent for myocardial membrane repair and cardioprotection, but its therapeutic value is complicated by its E3 ligase activity that mediates metabolic disorders. Here, we show that an E3 ligase-dead mutant, MG53-C14A, retains its cardioprotective function without causing metabolic side-effects. When administrated in normal animals, both recombinant human wild type MG53 protein (rhMG53-WT) and its E3 ligase-dead mutant (rhMG53-C14A) protect the heart equally from myocardial infarction and ischemia/reperfusion (I/R) injury. However, in diabetic <i>db/db</i> mice, rhMG53-WT treatment markedly aggravates hyperglycemia, cardiac I/R injury and mortality, whereas acute and chronic treatment of rhMG53-C14A still effectively ameliorates I/R-induced myocardial injury and mortality or diabetic cardiomyopathy, respectively, without inflicting metabolic side-effects. Furthermore, knock-in of MG53-C14A protects the mice from high-fat diet-induced metabolic disorders and cardiac damage. Thus, the E3 ligase-dead mutant MG53-C14A not only protects the heart from acute myocardial injury but also counteract metabolic stress, providing a potentially important therapy for the treatment of acute myocardial injuries amidst metabolic disorders, including diabetes and obesity.

scholarly journals MG53 E3 Ligase-dead Mutant Protects Diabetic Hearts from Acute Ischemic/Reperfusion Injury and Ameliorates Diet-induced Cardiometabolic Damage

2021 ◽  
Author(s):  
Han Feng ◽  
Hao Shen ◽  
Matthew J Robeson ◽  
Yue-Han Wu ◽  
Hong-Kun Wu ◽  
...  
Keyword(s):  
Side Effects ◽  
Metabolic Disorders ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Metabolic Stress ◽  
E3 Ligase ◽  
Cardiovascular Complications ◽  
Membrane Repair ◽  
Cardiac Damage ◽  
Metabolic Side Effects

Cardiometabolic diseases, including diabetes and its cardiovascular complications, are the global leading cause of death, highlighting a major unmet medical need. Over the last decade, MG53, also named TRIM72, has emerged as a powerful agent for myocardial membrane repair and cardioprotection, but its therapeutic value is complicated by its E3 ligase activity that mediates metabolic disorders. Here, we show that an E3 ligase-dead mutant, MG53-C14A, retains its cardioprotective function without causing metabolic side-effects. When administrated in normal animals, both recombinant human wild type MG53 protein (rhMG53-WT) and its E3 ligase-dead mutant (rhMG53-C14A) protect the heart equally from myocardial infarction and ischemia/reperfusion (I/R) injury. However, in diabetic <i>db/db</i> mice, rhMG53-WT treatment markedly aggravates hyperglycemia, cardiac I/R injury and mortality, whereas acute and chronic treatment of rhMG53-C14A still effectively ameliorates I/R-induced myocardial injury and mortality or diabetic cardiomyopathy, respectively, without inflicting metabolic side-effects. Furthermore, knock-in of MG53-C14A protects the mice from high-fat diet-induced metabolic disorders and cardiac damage. Thus, the E3 ligase-dead mutant MG53-C14A not only protects the heart from acute myocardial injury but also counteract metabolic stress, providing a potentially important therapy for the treatment of acute myocardial injuries amidst metabolic disorders, including diabetes and obesity.

Effects of intermittent hypoxia on oxidative stress-induced myocardial damage in mice

2007 ◽  
Vol 102 (5) ◽  
pp. 1806-1814 ◽  
Author(s):  
Ah-Mee Park ◽  
Yuichiro J. Suzuki
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Damage ◽  
Obstructive Sleep ◽  
Increased Risk

Obstructive sleep apnea is associated with increased risk for cardiovascular diseases. As obstructive sleep apnea is characterized by episodic cycles of hypoxia and normoxia during sleep, we investigated effects of intermittent hypoxia (IH) on ischemia-reperfusion-induced myocardial injury. C57BL/6 mice were subjected to IH (2 min 6% O2 and 2 min 21% O2) for 8 h/day for 1, 2, or 4 wk; isolated hearts were then subjected to ischemia-reperfusion. IH for 1 or 2 wk significantly enhanced ischemia-reperfusion-induced myocardial injury. However, enhanced cardiac damage was not seen in mice treated with 4 wk of IH, suggesting that the heart has adapted to chronic IH. Ischemia-reperfusion-induced lipid peroxidation and protein carbonylation were enhanced with 2 wk of IH, while, with 4 wk, oxidative stress was normalized to levels in animals without IH. H2O2 scavenging activity in adapted hearts was higher after ischemia-reperfusion, suggesting the increased antioxidant capacity. This might be due to the involvement of thioredoxin, as the expression level of this protein was increased, while levels of other antioxidant enzymes were unchanged. In the heart from mice treated with 2 wk of IH, ischemia-reperfusion was found to decrease thioredoxin. Ischemia-reperfusion injury can also be enhanced when thioredoxin reductase was inhibited in control hearts. These results demonstrate that IH changes the susceptibility of the heart to oxidative stress in part via alteration of thioredoxin.

CLINICAL CHALLENGES FOR ANESTHESIOLOGIST FACING PATIENT WITH ACROMEGALY. CASE REPORT

2020 ◽  
Vol 30 (3) ◽  
pp. 56-59
Author(s):  
Jūratė Gudaitytė ◽  
Justina Jermolajevaitė ◽  
Martynas Judickas
Keyword(s):  
Atrial Fibrillation ◽  
Case Report ◽  
General Population ◽  
Metabolic Disorders ◽  
Upper Airway ◽  
Cardiovascular Complications ◽  
Case Presentation ◽  
Increased Risk ◽  
Fluid Regulation ◽  
Class Iv

Background and objectives: Acromegaly is endocri­nal disorder which results in changes involving ge­neral appearance as well as upper airway abnorma­lities, cardiovascular and metabolic disorders which can aggravate the anesthesia and can lead to compli­cations. We aim to discuss the challenges for anesthe­siologist that occurs facing patient with acromegaly and are necessary to investigate before performing any kind of intervention. Case Presentation: 79 years old male patient presen­ted the hospital with recently diagnosed acromegaly for rectal prolapse surgery. From anamnesis he had NYHAIII with cardiomyopathy, atrial fibrillation and arterial hypertension, also multiple old compressive fractures Th10 – L5. He was graded with Mallam­pati score IV and ASA class IV. The complemen­tary examinations were made to assess the possible complications. In induction of general anesthesia the intubation was performed using fibro- bronchoscope and anesthesia went without complications except hypotension which was managed. After surgery the patient was leaded to the postoperative room for furt­her monitoring. Discussion and Conclusion: Acromegalic patients have an increased risk of difficulty during anesthe­sia compared to general population due to difficult intubation, cardiovascular complications , OSA , alte­ration in intraoperative glucose intolerance and fluid regulation. Therefore profound investigation and as­sessment are necessary to predict and prepare for possible difficulties in the surgery room.

Ginger and Heart Health: From Mechanisms to Therapeutics

2020 ◽  
Vol 13 ◽  
Author(s):  
Sajad Fakhri ◽  
Jayanta Kumar Patra ◽  
Swagat Kumar Das ◽  
Gitishree Das ◽  
Mohammad Bagher Majnooni ◽  
...  
Keyword(s):  
Side Effects ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Health Benefits ◽  
Herbal Medicines ◽  
Cardiovascular Complications ◽  
National Database ◽  
Heart Health ◽  
Natural Entities ◽  
Cardioprotective Effects

Background: As a major cause of morbidity and mortality, cardiovascular diseases (CVDs) are globally increasing. In spite of recent development in the management of cardiovascular complications, CVDs have remained a medical challenge. Numerous conventional drugs are used to play cardioprotective roles; however, they are associated with several side effects. Considering the rich phytochemistry and fewer side effects of herbal medicines, they have gained particular attention to develop novel herbal drugs with cardioprotective potentials. Amongst natural entities, ginger is an extensively used and well-known functional food and condiment, possessing plentiful bioactivities, like antiinflammatory, antioxidant, and antimicrobial properties in several disorders management. Objective: The current review deliberated phytochemical properties as well as the ginger/ginger constituents' biological activities and health benefits in several diseases, with particular attention to cardiovascular complications. Methods: A comprehensive research was conducted using multiple databases, including Scopus, PubMed, Medline, Web of Science, national database (Irandoc and SID), and related articles in terms of the health benefits and cardioprotective effects of ginger/ginger constituents. These data were collected from inception until August 2019. Results: In recent years, several herbal medicines were used to develop new drugs with more potency and also minor side effects. Amongst natural entities, ginger is an extensively used traditional medicine in several diseases. The crude extract, along with related pungent active constituents, is mostly attributed to heart health. The cardioprotective effects of ginger are contributed to its cardiotonic, antihypertensive, anti-hyperlipidemia, and anti-platelet effects. The signaling pathways and molecular mechanisms of ginger regarding its cardioprotective effects are also clarified. Conclusion: This study revealed the biological activities, health benefits, and cardioprotective properties of ginger/ginger constituents along with related mechanisms of action, which gave new insights to show new avenue in the treatment of CVDs.

scholarly journals Focal ST-segment elevation without coronary occlusion: myocardial infarction with no obstructive coronary atherosclerosis associated with COVID-19—a case report

2021 ◽  
Vol 5 (2) ◽  
Author(s):  
Casey Meizinger ◽  
Bruce Klugherz
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Respiratory Failure ◽  
Coronary Atherosclerosis ◽  
Myocardial Injury ◽  
Cardiovascular Complications ◽  
St Segment Elevation ◽  
St Segment ◽  
Hypoxic Respiratory Failure ◽  
Artery Disease

Abstract Background While it is understood that coronavirus disease 2019 (COVID-19) is primarily complicated by respiratory failure, more data are emerging on the cardiovascular complications of this disease. A subset of COVID-19 patients present with ST-elevations on electrocardiogram (ECG) yet normal coronary angiography, a presentation that can fit criteria for myocardial infarction with no obstructive coronary atherosclerosis (MINOCA). There is little known about non-coronary myocardial injury observed in patients with COVID-19, and we present a case that should encourage further conversation and study of this clinical challenge. Case summary An 86-year-old man presented to our institution with acute hypoxic respiratory failure and an ECG showing anteroseptal ST-segment elevation concerning for myocardial infarction. Mechanic ventilation was initiated prior to presentation, and emergent transthoracic echocardiography reported an ejection fraction of 50–55%, with no significant regional wall motion abnormalities. Next, emergent coronary angiography was performed, and no significant coronary artery disease was detected. The patient tested positive for COVID-19. Despite supportive management in the intensive care unit, the patient passed away. Discussion We present a case of COVID-19 that is likely associated with MINOCA. It is crucial to understand that in COVID-19 patients with signs of myocardial infarction, not all myocardial injury is due to obstructive coronary artery disease. In the case of COVID-19 pathophysiology, it is important to consider the cardiovascular effects of hypoxic respiratory failure, potential myocarditis, and significant systemic inflammation. Continued surveillance and research on the cardiovascular complications of COVID-19 is essential to further elucidate management and prognosis.

scholarly journals ST-Elevation Myocardial Infarction and COVID-19 Pneumonia: The Importance of Risk-Stratification of Myocardial Injury in COVID-19 Era

2021 ◽  
pp. 263246362199238
Author(s):  
Julio C. Sauza-Sosa ◽  
Oscar Millan-Iturbe ◽  
Jorge Mendoza-Ramirez ◽  
Carlos N. Velazquez-Gutierrez ◽  
Erika Lizeth De la Cruz Reyna ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Injury Risk ◽  
Myocardial Injury ◽  
Cardiovascular Complications ◽  
Adverse Outcomes ◽  
St Elevation ◽  
Diagnostic Coronary Angiography ◽  
Serial Measurements ◽  
Initial Classification

Background: Myocardial injury is a common manifestation in patients with coronavirus disease (COVID-19), and the correlation with adverse outcomes has been demonstrated; therefore, adequate monitoring of myocardial injury markers is very important. Case Summary: A patient with COVID-19 was hospitalized in our hospital with an initial classification of intermediate risk for myocardial injury, after serial measurements of myocardial injury markers, risk was readjusted to high, as shown later by electrocardiographic abnormalities. The patient underwent emergency diagnostic coronary angiography and successful angioplasty. The patient was discharged to home. Discussion: Myocardial injury risk-stratification is essential in patients with COVID-19, since it is essential in the recognition of patients who are susceptible to cardiovascular complications.

Effect of liraglutide on neural and peripheral markers of metabolic function during antipsychotic treatment in rats

2021 ◽  
Vol 35 (3) ◽  
pp. 284-302
Author(s):  
Ilijana Babic ◽  
Dominic Sellers ◽  
Paul L Else ◽  
Jessica Nealon ◽  
Ashleigh L Osborne ◽  
...  
Keyword(s):  
Side Effects ◽  
Chronic Treatment ◽  
Antipsychotic Treatment ◽  
Metabolic Markers ◽  
Metabolic Side Effects ◽  
Feeding Efficiency ◽  
Adaptive Mechanisms ◽  
Liver And Kidney ◽  
Glucagon Like Peptide 1 ◽  
Peripheral Markers

Background: Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that prevents metabolic side effects of the antipsychotic drugs (APDs) olanzapine and clozapine through unknown mechanisms. Aim: This study aimed to investigate the effect of chronic APD and liraglutide co-treatment on key neural and peripheral metabolic signals, and acute liraglutide co-treatment on clozapine-induced hyperglycaemia. Methods: In study 1, rats were administered olanzapine (2 mg/kg), clozapine (12 mg/kg), liraglutide (0.2 mg/kg), olanzapine + liraglutide co-treatment, clozapine + liraglutide co-treatment or vehicle for six weeks. Feeding efficiency was examined weekly. Examination of brain tissue (dorsal vagal complex (DVC) and mediobasal hypothalamus (MBH)), plasma metabolic hormones and peripheral (liver and kidney) cellular metabolism and oxidative stress was conducted. In study 2, rats were administered a single dose of clozapine (12 mg/kg), liraglutide (0.4 mg/kg), clozapine + liraglutide co-treatment or vehicle. Glucose tolerance and plasma hormone levels were assessed. Results: Liraglutide co-treatment prevented the time-dependent increase in feeding efficiency caused by olanzapine, which plateaued by six weeks. There was no effect of chronic treatment on melanocortinergic, GABAergic, glutamatergic or endocannabionoid markers in the MBH or DVC. Peripheral hormones and cellular metabolic markers were unaltered by chronic APD treatment. Acute liraglutide co-treatment was unable to prevent clozapine-induced hyperglycaemia, but it did alter catecholamine levels. Conclusion: The unexpected lack of change to central and peripheral markers following chronic treatment, despite the presence of weight gain, may reflect adaptive mechanisms. Further studies examining alterations across different time points are required to continue to elucidate the mechanisms underlying the benefits of liraglutide on APD-induced metabolic side effects.

Overexpression of miR-431 attenuates hypoxia/reoxygenation-induced myocardial damage via autophagy-related 3

2020 ◽  
Author(s):  
Kang Zhou ◽  
Yan Xu ◽  
Qiong Wang ◽  
Lini Dong
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Protective Role ◽  
Human Cardiomyocytes ◽  
Hypoxia Reoxygenation

Abstract Myocardial injury is still a serious condition damaging the public health. Clinically, myocardial injury often leads to cardiac dysfunction and, in severe cases, death. Reperfusion of the ischemic myocardial tissues can minimize acute myocardial infarction (AMI)-induced damage. MicroRNAs are commonly recognized in diverse diseases and are often involved in the development of myocardial ischemia/reperfusion injury. However, the role of miR-431 remains unclear in myocardial injury. In this study, we investigated the underlying mechanisms of miR-431 in the cell apoptosis and autophagy of human cardiomyocytes in hypoxia/reoxygenation (H/R). H/R treatment reduced cell viability, promoted cell apoptotic rate, and down-regulated the expression of miR-431 in human cardiomyocytes. The down-regulation of miR-431 by its inhibitor reduced cell viability and induced cell apoptosis in the human cardiomyocytes. Moreover, miR-431 down-regulated the expression of autophagy-related 3 (ATG3) via targeting the 3ʹ-untranslated region of ATG3. Up-regulated expression of ATG3 by pcDNA3.1-ATG3 reversed the protective role of the overexpression of miR-431 on cell viability and cell apoptosis in H/R-treated human cardiomyocytes. More importantly, H/R treatments promoted autophagy in the human cardiomyocytes, and this effect was greatly alleviated via miR-431-mimic transfection. Our results suggested that miR-431 overexpression attenuated the H/R-induced myocardial damage at least partly through regulating the expression of ATG3.

Sign in / Sign up

Export Citation Format

Share Document