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Cureus May 2024This case report delineates the clinical trajectory and management strategies of a 59-year-old Hispanic male diagnosed with a left ventricular pseudoaneurysm (LVPA)...
This case report delineates the clinical trajectory and management strategies of a 59-year-old Hispanic male diagnosed with a left ventricular pseudoaneurysm (LVPA) following a delayed presentation of ST-segment elevation myocardial infarction (STEMI), for which reperfusion treatment was not administered. Initially, an echocardiogram demonstrated an extensive anterolateral myocardial infarction, severe left ventricular systolic dysfunction, and an early-stage left ventricular apical aneurysm with thrombus, leading to the initiation of warfarin. Metabolic myocardial perfusion imaging via positron emission tomography indicated a substantial myocardial scar without viability, guiding the decision against revascularization. Post discharge, the patient, equipped with a wearable cardioverter defibrillator for sudden cardiac death prevention, experienced symptomatic ventricular tachycardia, which was resolved with defibrillator shocks. Subsequent imaging revealed an acute LVPA adjacent to the existing left ventricular aneurysm. Given the high surgical risk, conservative management was elected, resulting in thrombosis and closure of the pseudoaneurysm after two weeks. The patient eventually transitioned to home hospice, surviving an additional five months. This report underscores the complexities and therapeutic dilemmas in managing post-MI LVPA patients who are ineligible for surgical intervention.
PubMed: 38854241
DOI: 10.7759/cureus.60026 -
BioRxiv : the Preprint Server For... Jun 2024We and others discovered a highly-conserved mitochondrial transmembrane microprotein, named Mitoregulin (Mtln), that supports lipid metabolism. We reported that Mtln...
We and others discovered a highly-conserved mitochondrial transmembrane microprotein, named Mitoregulin (Mtln), that supports lipid metabolism. We reported that Mtln strongly binds cardiolipin (CL), increases mitochondrial respiration and Ca retention capacities, and reduces reactive oxygen species (ROS). Here we extend our observation of Mtln-CL binding and examine Mtln influence on cristae structure and mitochondrial membrane integrity during stress. We demonstrate that mitochondria from constitutive- and inducible Mtln-knockout (KO) mice are susceptible to membrane freeze-damage and that this can be rescued by acute Mtln re-expression. In mitochondrial-simulated lipid monolayers, we show that synthetic Mtln decreases lipid packing and monolayer elasticity. Lipidomics revealed that Mtln-KO heart tissues show broad decreases in 22:6-containing lipids and increased cardiolipin damage/remodeling. Lastly, we demonstrate that Mtln-KO mice suffer worse myocardial ischemia-reperfusion injury, hinting at a translationally-relevant role for Mtln in cardioprotection. Our work supports a model in which Mtln binds cardiolipin and stabilizes mitochondrial membranes to broadly influence diverse mitochondrial functions, including lipid metabolism, while also protecting against stress.
PubMed: 38853979
DOI: 10.1101/2024.05.31.596875 -
Biomedicine & Pharmacotherapy =... Jul 2024Integrated stress response (ISR) is activated to promote cell survival by maintaining the phosphorylation of eukaryotic translation initiation factor 2 (eIF2α). We...
OBJECTIVE
Integrated stress response (ISR) is activated to promote cell survival by maintaining the phosphorylation of eukaryotic translation initiation factor 2 (eIF2α). We investigated whether Sephin1 enhances ISR and attenuates myocardial ischemia-reperfusion (MIR) injury.
METHODS
Male C57BL/6 J mice were injected with Sephin1 (2 mg/kg,i.p.) 30 min before surgery to establish a model of MIR with 45 min ischemia and 180 min reperfusion. In vitro, the H9C2 cell line with hypoxia-reoxygenation (H/R) was used to simulate MIR. Myocardial injury was evaluated by echocardiography, histologic observation after staining with TTC and H&E and electron microscopy. ISR, autophagy and apoptosis in vivo and in vitro were evaluated by immunoblotting, immunohistochemistry, immunofluorescence, and flow cytometry, respectively. Global protein synthesis was determined using a non-radioactive SUnSET Assay based on the puromycin method. Autophinib, an autophagy-specific inhibitor, was used to investigate the correlation between autophagy and apoptosis in the presence of Sephin1.
RESULTS
In vivo, Sephin1 significantly reduced myocardial injury and improved the cardiac function in MIR mice. Sephin1 administration prolonged ISR, reduced cell apoptosis, and promoted autophagy. In vitro, Sephin1 increased the number of stress granules (SGs) and autophagic vesicles, enhanced ISR and related protein synthesis suppression, and reduced cell apoptosis. Autophinib partly reversed autophagosome formation and apoptosis in H9c2 cells.
CONCLUSIONS
Sephin1 enhances ISR and related protein synthesis suppression, ameliorates myocardial apoptosis, and promotes autophagy during MIR stress. Sephin1 could act as a noval ISR enhancer for managing acute myocardial ischemia disease.
Topics: Animals; Autophagy; Male; Myocardial Reperfusion Injury; Mice, Inbred C57BL; Mice; Apoptosis; Cell Line; Myocytes, Cardiac; Disease Models, Animal; Erythropoietin; Peptide Fragments
PubMed: 38850665
DOI: 10.1016/j.biopha.2024.116869 -
Scientific Reports Jun 2024Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a feasible and effective rescue strategy for prolonged cardiac arrest (CA). However, prolonged total...
Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a feasible and effective rescue strategy for prolonged cardiac arrest (CA). However, prolonged total body ischemia and reperfusion can cause microvascular occlusion that prevents organ reperfusion and recovery of function. One hypothesized mechanism of microvascular "no-reflow" is leukocyte adhesion and formation of neutrophil extracellular traps. In this study we tested the hypothesis that a leukocyte filter (LF) or leukocyte modulation device (L-MOD) could reduce NETosis and improve recovery of heart and brain function in a swine model of prolonged cardiac arrest treated with ECPR. Thirty-six swine (45.5 ± 2.5 kg, evenly distributed sex) underwent 8 min of untreated ventricular fibrillation CA followed by 30 min of mechanical CPR with subsequent 8 h of ECPR. Two females were later excluded from analysis due to CPR complications. Swine were randomized to standard care (Control group), LF, or L-MOD at the onset of CPR. NET formation was quantified by serum dsDNA and citrullinated histone as well as immunofluorescence staining of the heart and brain for citrullinated histone in the microvasculature. Primary outcomes included recovery of cardiac function based on cardiac resuscitability score (CRS) and recovery of neurologic function based on the somatosensory evoked potential (SSEP) N20 cortical response. In this model of prolonged CA treated with ECPR we observed significant increases in serum biomarkers of NETosis and immunohistochemical evidence of microvascular NET formation in the heart and brain that were not reduced by LF or L-MOD therapy. Correspondingly, there were no significant differences in CRS and SSEP recovery between Control, LF, and L-MOD groups 8 h after ECPR onset (CRS = 3.1 ± 2.7, 3.7 ± 2.6, and 2.6 ± 2.6 respectively; p = 0.606; and SSEP = 27.9 ± 13.0%, 36.7 ± 10.5%, and 31.2 ± 9.8% respectively, p = 0.194). In this model of prolonged CA treated with ECPR, the use of LF or L-MOD therapy during ECPR did not reduce microvascular NETosis or improve recovery of myocardial or brain function. The causal relationship between microvascular NETosis, no-reflow, and recovery of organ function after prolonged cardiac arrest treated with ECPR requires further investigation.
Topics: Animals; Heart Arrest; Cardiopulmonary Resuscitation; Swine; Female; Disease Models, Animal; Male; Extracorporeal Membrane Oxygenation; Leukocytes; Extracellular Traps; Leukocyte Reduction Procedures
PubMed: 38844477
DOI: 10.1038/s41598-024-63522-w -
Nutrition & Diabetes Jun 2024Insulin resistance (IR) is indicated to be linked with adverse outcomes of acute myocardial infarction (AMI), for its pro-inflammatory and pro-thromboplastic function.... (Meta-Analysis)
Meta-Analysis Review
The association of triglyceride-glucose index with major adverse cardiovascular and cerebrovascular events after acute myocardial infarction: a meta-analysis of cohort studies.
BACKGROUND
Insulin resistance (IR) is indicated to be linked with adverse outcomes of acute myocardial infarction (AMI), for its pro-inflammatory and pro-thromboplastic function. The triglyceride-glucose (TyG) index is a newly developed substitute marker for IR. The aim of this pooled analysis was to provide a summary of the relationship of TyG index with occurrences of major adverse cardiovascular and cerebrovascular events (MACCEs) among populations suffering from AMI.
METHODS
Cohorts reporting multivariate-adjusted hazard ratios of TyG index with MACCEs or its independent events were identified through systematically searching PubMed, MEDLINE, Web of science, Embase and Cochrane databases. Results were combined using a random-effects model.
RESULTS
21 cohorts comprising 20403 individuals were included. Compared to individuals in the lowest TyG category, patients in the highest TyG category exhibited elevated risks of both MACCEs (P < 0.00001) and all-cause death (P < 0.00001). These findings were in line with the results as TyG analyzed as continuous variables (MACCEs: P = 0.006; all-cause death: P < 0.00001). Subgroup analysis demonstrated that diabetic status, type of AMI, nor the reperfusion therapy did not destruct this correlation (for subgroups, all P < 0.05).
CONCLUSION
All these indicated that higher TyG index could potentially predict MACCEs and all-cause death in patients with AMI as an independent indicator.
Topics: Humans; Myocardial Infarction; Triglycerides; Blood Glucose; Cerebrovascular Disorders; Cardiovascular Diseases; Insulin Resistance; Cohort Studies; Risk Factors; Biomarkers
PubMed: 38844442
DOI: 10.1038/s41387-024-00295-1 -
PloS One 2024Type 2 diabetes predisposes patients to heart disease, which is the primary cause of death across the globe. Type 2 diabetes often accompanies obesity and is defined by...
Type 2 diabetes predisposes patients to heart disease, which is the primary cause of death across the globe. Type 2 diabetes often accompanies obesity and is defined by insulin resistance and abnormal glucose handling. Insulin resistance impairs glucose uptake and results in hyperglycemia, which damages tissues such as kidneys, liver, and heart. 2-oxoglutarate (2-OG)- and iron-dependent oxygenases (2-OGDOs), a family of enzymes regulating various aspects of cellular physiology, have been studied for their role in obesity and diet-induced insulin resistance. However, nothing is known of the 2-OGDO family member 2-oxoglutarate and iron-dependent prolyl hydroxylase domain containing protein 1 (OGFOD1) in this setting. OGFOD1 deletion leads to protection in cardiac ischemia-reperfusion injury and cardiac hypertrophy, which are two cardiac events that can lead to heart failure. Considering the remarkable correlation between heart disease and diabetes, the cardioprotection observed in OGFOD1-knockout mice led us to challenge these knockouts with high-fat diet. Wildtype mice fed a high-fat diet developed diet-induced obesity, insulin resistance, and glucose intolerance, but OGFOD1 knockout mice fed this same diet were resistant to diet-induced obesity and insulin resistance. These results support OGFOD1 down-regulation as a strategy for preventing obesity and insulin handling defects.
Topics: Animals; Insulin Resistance; Obesity; Mice; Diet, High-Fat; Mice, Knockout; Male; Prolyl Hydroxylases; Glucose Intolerance; Mice, Inbred C57BL; Gene Deletion; Cardiomegaly; Myocardial Reperfusion Injury
PubMed: 38843265
DOI: 10.1371/journal.pone.0304761 -
Cell & Bioscience Jun 2024Cardiovascular diseases (CVDs) have emerged as a predominant threat to human health, surpassing the incidence and mortality rates of neoplastic diseases. Extracellular... (Review)
Review
Cardiovascular diseases (CVDs) have emerged as a predominant threat to human health, surpassing the incidence and mortality rates of neoplastic diseases. Extracellular vesicles (EVs) serve as vital mediators in intercellular communication and material exchange. Endothelial progenitor cells (EPCs), recognized as precursors of vascular endothelial cells (ECs), have garnered considerable attention in recent years due to the potential therapeutic value of their derived extracellular vesicles (EPC-EVs) in the context of CVDs. This comprehensive review systematically explores the origins, characteristics, and functions of EPCs, alongside the classification, properties, biogenesis, and extraction techniques of EVs, with particular emphasis on their protective roles in CVDs. Additionally, we delve into the essential bioactive components of EPC-EVs, including microRNAs, long non-coding RNAs, and proteins, analyzing their beneficial effects in promoting angiogenesis, anti-inflammatory and anti-oxidant activities, anti-fibrosis, anti-apoptosis, and myocardial regeneration. Furthermore, this review comprehensively investigates the therapeutic potential of EPC-EVs across various CVDs, encompassing acute myocardial infarction, myocardial ischemia-reperfusion injury, atherosclerosis, non-ischemic cardiomyopathies, and diabetic cardiovascular disease. Lastly, we summarize the potential challenges associated with the clinical application of EPC-EVs and outline future directions, aiming to offer a valuable resource for both theoretical insights and practical applications of EPC-EVs in managing CVDs.
PubMed: 38840175
DOI: 10.1186/s13578-024-01255-z -
Scientific Reports Jun 2024Growth/differentiation factor-15 (GDF15) is considered an unfavourable prognostic biomarker for cardiovascular disease in clinical data, while experimental studies...
Growth/differentiation factor-15 (GDF15) is considered an unfavourable prognostic biomarker for cardiovascular disease in clinical data, while experimental studies suggest it has cardioprotective potential. This study focuses on the direct cardiac effects of GDF15 during ischemia-reperfusion injury in Wistar male rats, employing concentrations relevant to patients at high cardiovascular risk. Initially, we examined circulating levels and heart tissue expression of GDF15 in rats subjected to ischemia-reperfusion and sham operations in vivo. We then evaluated the cardiac effects of GDF15 both in vivo and ex vivo, administering recombinant GDF15 either before 30 min of ischemia (preconditioning) or at the onset of reperfusion (postconditioning). We compared infarct size and cardiac contractile recovery between control and rGDF15-treated rats. Contrary to our expectations, ischemia-reperfusion did not increase GDF15 plasma levels compared to sham-operated rats. However, cardiac protein and mRNA expression increased in the infarcted zone of the ischemic heart after 24 h of reperfusion. Notably, preconditioning with rGDF15 had a cardioprotective effect, reducing infarct size both in vivo (65 ± 5% in control vs. 42 ± 6% in rGDF15 groups) and ex vivo (60 ± 4% in control vs. 45 ± 4% in rGDF15 groups), while enhancing cardiac contractile recovery ex vivo. However, postconditioning with rGDF15 did not alter infarct size or the recovery of contractile parameters in vivo or ex vivo. These novel findings reveal that the short-term exogenous administration of rGDF15 before ischemia, at physiologically relevant levels, protects the heart against ischemia-reperfusion injury in both in vivo and ex vivo settings. The ex vivo results indicate that rGDF15 operates independently of the inflammatory, endocrine and nervous systems, suggesting direct and potent cardioprotective properties against ischemia-reperfusion injury.
Topics: Growth Differentiation Factor 15; Animals; Male; Myocardial Infarction; Rats, Wistar; Rats; Myocardial Reperfusion Injury; Myocardium; Cardiotonic Agents; Recombinant Proteins; Ischemic Preconditioning, Myocardial
PubMed: 38839839
DOI: 10.1038/s41598-024-63880-5 -
Biomedicine & Pharmacotherapy =... Jul 2024Our previous research discovered that cinnamamide derivatives are a new type of potential cardioprotective agents myocardial ischemia-reperfusion (MIR) injury, among...
BACKGROUND AND PURPOSE
Our previous research discovered that cinnamamide derivatives are a new type of potential cardioprotective agents myocardial ischemia-reperfusion (MIR) injury, among which Compound 10 exhibits wonderful beneficial action in vitro. However, the exact mechanism of Compound 10 still needs to be elucidated.
EXPERIMENTAL APPROACH
The protective effect of Compound 10 was determined by detecting the cell viability and LDH leakage rate in H9c2 cells subjected to HO Alterations of electrocardiogram, echocardiography, cardiac infarct area, histopathology and serum myocardial zymogram were tested in MIR rats. Additionally, the potential mechanism of Compound 10 was explored through PCR. Network pharmacology and Western blotting was conducted to monitor levels of proteins related to autophagic flux and mTOR, autophagy regulatory substrate, induced by Compound 10 both in vitro and in vivo, as well as expressions of Sirtuins family members.
KEY RESULTS
Compound 10 significantly ameliorated myocardial injury, as demonstrated by increased cell viability, decreased LDH leakage in vitro, and declined serum myocardial zymogram, ST elevation, cardiac infarct area and improved cardiac function and microstructure of heart tissue in vivo. Importantly, Compound 10 markedly enhanced the obstruction of autophagic flux and inhibited excessive autophagy initiation against MIR by decreased ATG5, Rab7 and increased P-mTOR and LAMP2. Furthermore, Sirt1 knockdown hindered Compound 10's regulation on mTOR, leading to interrupted cardiac autophagic flux.
CONCLUSIONS AND IMPLICATIONS
Compound 10 exerted cardioprotective effects on MIR by reducing excessive autophagy and improving autophgic flux blockage. Our work would take a novel insight in seeking effective prevention and treatment strategies against MIR injury.
Topics: Animals; Male; Rats; Autophagy; Cardiotonic Agents; Cell Line; Cell Survival; Cinnamates; Myocardial Reperfusion Injury; Myocytes, Cardiac; Rats, Sprague-Dawley; Sirtuin 1
PubMed: 38834003
DOI: 10.1016/j.biopha.2024.116819 -
International Heart Journal 2024Myocardial infarction/reperfusion (I/R) injury significantly impacts the health of older individuals. We confirmed that the level of lncRNA Peg13 was downregulated in...
Myocardial infarction/reperfusion (I/R) injury significantly impacts the health of older individuals. We confirmed that the level of lncRNA Peg13 was downregulated in I/R injury. However, the detailed function of Peg13 in myocardial I/R injury has not yet been explored.To detect the function of Peg13, in vivo model of I/R injury was constructed. RT-qPCR was employed to investigate RNA levels, and Western blotting was performed to assess levels of endoplasmic reticulum stress and apoptosis-associated proteins. EdU staining was confirmed to assess the cell proliferation.I/R therapy dramatically produced myocardial injury, increased the infarct area, and decreased the amount of Peg13 in myocardial tissues of mice. In addition, hypoxia/reoxygenation (H/R) notably induced the apoptosis and promoted the endoplasmic reticulum (ER) stress of HL-1 cells, while overexpression of Peg13 reversed these phenomena. Additionally, Peg13 may increase the level of Sirt1 through binding to miR-34a. Upregulation of Peg13 reversed H/R-induced ER stress via regulation of miR-34a/Sirt1 axis.LncRNA Peg13 reduces ER stress in myocardial infarction/reperfusion injury through mediation of miR-34a/Sirt1 axis. Hence, our research might shed new lights on developing new strategies for the treatment of myocardial I/R injury.
Topics: Animals; Endoplasmic Reticulum Stress; MicroRNAs; RNA, Long Noncoding; Sirtuin 1; Myocardial Reperfusion Injury; Mice; Male; Myocardial Infarction; Apoptosis; Disease Models, Animal; Mice, Inbred C57BL
PubMed: 38825496
DOI: 10.1536/ihj.23-453