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Biomedicine & Pharmacotherapy =... Jan 2022Ferroptosis is a programmed iron-dependent cell death characterized by accumulation of lipid peroxides (LOOH) and redox disequilibrium. Ferroptosis shows unique...
Ferroptosis is a programmed iron-dependent cell death characterized by accumulation of lipid peroxides (LOOH) and redox disequilibrium. Ferroptosis shows unique characteristics in biology, chemistry, and gene levels, compared to other cell death forms. The metabolic disorder of intracellular LOOH catalyzed by iron causes the inactivity of GPX4, disrupts the redox balance, and triggers cell death. Metabolism of amino acid, iron, and lipid, including associated pathways, is considered as a specific hallmark of ferroptosis. Epidemiological studies and animal experiments have shown that ferroptosis plays an important character in the pathophysiology of cardiovascular disease such as atherosclerosis, myocardial infarction (MI), ischemia/reperfusion (I/R), heart failure (HF), cardiac hypertrophy, cardiomyopathy, and abdominal aortic aneurysm (AAA). This review systematically summarized the latest research progress on the mechanisms of ferroptosis. Then we report the contribution of ferroptosis in cardiovascular diseases. Finally, we discuss and analyze the therapeutic approaches targeting for ferroptosis associated with cardiovascular diseases.
Topics: Animals; Cardiovascular Diseases; Cell Death; Ferroptosis; Humans; Lipid Peroxides; Metabolic Diseases; Oxidation-Reduction
PubMed: 34800783
DOI: 10.1016/j.biopha.2021.112423 -
International Journal of Cardiology.... Jun 2023Despite the success of interventional coronary reperfusion strategies, morbidity and mortality from acute myocardial infarction are still substantial. Physical exercise... (Review)
Review
BACKGROUND
Despite the success of interventional coronary reperfusion strategies, morbidity and mortality from acute myocardial infarction are still substantial. Physical exercise is a well-recognized effective non-pharmacological therapy for cardiovascular diseases. Therefore, the objective of this systematic review was to analyze studies in animal models of ischemia-reperfusion in association with physical exercise protocols.
SEARCH STRATEGY
Articles published on the topic over a 13-year period (2010-2022) were searched in two databases (PubMed and Google Scholar) using the keywords exercise training, ischemia/reperfusion or ischemia reperfusion injury. Meta-analysis and quality assessment of the studies were performed using the Review Manager 5.3 program.
RESULTS
From the 238 articles retrieved from PubMed and 200 from Google Scholar, after screening and eligibility assessment, 26 articles were included in the systematic review and meta-analysis. For meta-analysis comparing the group of previously exercised animals with the non-exercised animals and then submitted to ischemia-reperfusion, the infarct size was significantly decreased by exercise (p < 0.00001). In addition, the group exercised had increased heart-to-body weight ratio (p < 0.00001) and improved ejection fraction as measured by echocardiography (p < 0.0004) in comparison to non-exercised animals.
CONCLUSION
We concluded that the animal models of ischemia-reperfusion indicates that exercise reduce infarct size and preserve ejection fraction, associated with beneficial myocardial remodeling.
PubMed: 37181278
DOI: 10.1016/j.ijcha.2023.101214 -
Pharmacological Reviews Apr 2021The complement system was discovered at the end of the 19th century as a heat-labile plasma component that "complemented" the antibodies in killing microbes, hence the...
The complement system was discovered at the end of the 19th century as a heat-labile plasma component that "complemented" the antibodies in killing microbes, hence the name "complement." Complement is also part of the innate immune system, protecting the host by recognition of pathogen-associated molecular patterns. However, complement is multifunctional far beyond infectious defense. It contributes to organ development, such as sculpting neuron synapses, promoting tissue regeneration and repair, and rapidly engaging and synergizing with a number of processes, including hemostasis leading to thromboinflammation. Complement is a double-edged sword. Although it usually protects the host, it may cause tissue damage when dysregulated or overactivated, such as in the systemic inflammatory reaction seen in trauma and sepsis and severe coronavirus disease 2019 (COVID-19). Damage-associated molecular patterns generated during ischemia-reperfusion injuries (myocardial infarction, stroke, and transplant dysfunction) and in chronic neurologic and rheumatic disease activate complement, thereby increasing damaging inflammation. Despite the long list of diseases with potential for ameliorating complement modulation, only a few rare diseases are approved for clinical treatment targeting complement. Those currently being efficiently treated include paroxysmal nocturnal hemoglobinuria, atypical hemolytic-uremic syndrome, myasthenia gravis, and neuromyelitis optica spectrum disorders. Rare diseases, unfortunately, preclude robust clinical trials. The increasing evidence for complement as a pathogenetic driver in many more common diseases suggests an opportunity for future complement therapy, which, however, requires robust clinical trials; one ongoing example is COVID-19 disease. The current review aims to discuss complement in disease pathogenesis and discuss future pharmacological strategies to treat these diseases with complement-targeted therapies. SIGNIFICANCE STATEMENT: The complement system is the host's defense friend by protecting it from invading pathogens, promoting tissue repair, and maintaining homeostasis. Complement is a double-edged sword, since when dysregulated or overactivated it becomes the host's enemy, leading to tissue damage, organ failure, and, in worst case, death. A number of acute and chronic diseases are candidates for pharmacological treatment to avoid complement-dependent damage, ranging from the well established treatment for rare diseases to possible future treatment of large patient groups like the pandemic coronavirus disease 2019.
Topics: COVID-19; Collectins; Complement Activating Enzymes; Complement C3; Complement Inactivating Agents; Complement System Proteins; Genetic Therapy; Humans; Inflammation Mediators; Lectins; Mannose-Binding Protein-Associated Serine Proteases; Pandemics; Rare Diseases; SARS-CoV-2; Synapses; Ficolins
PubMed: 33687995
DOI: 10.1124/pharmrev.120.000072 -
Lipids in Health and Disease Feb 2024Myocardial ischemia-reperfusion injury (MIRI) is widespread in the treatment of ischemic heart disease, and its treatment options are currently limited. Adiponectin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Myocardial ischemia-reperfusion injury (MIRI) is widespread in the treatment of ischemic heart disease, and its treatment options are currently limited. Adiponectin (APN) is an adipocytokine with cardioprotective properties; however, the mechanisms of APN in MIRI are unclear. Therefore, based on preclinical (animal model) evidence, the cardioprotective effects of APN and the underlying mechanisms were explored.
METHODS
The literature was searched for the protective effect of APN on MIRI in six databases until 16 November 2023, and data were extracted according to selection criteria. The outcomes were the size of the myocardial necrosis area and hemodynamics. Markers of oxidation, apoptosis, and inflammation were secondary outcome indicators. The quality evaluation was performed using the animal study evaluation scale recommended by the Systematic Review Center for Laboratory animal Experimentation statement. Stata/MP 14.0 software was used for the summary analysis.
RESULTS
In total, 20 papers with 426 animals were included in this study. The pooled analysis revealed that APN significantly reduced myocardial infarct size [weighted mean difference (WMD) = 16.67 (95% confidence interval (CI) = 13.18 to 20.16, P < 0.001)] and improved hemodynamics compared to the MIRI group [Left ventricular end-diastolic pressure: WMD = 5.96 (95% CI = 4.23 to 7.70, P < 0.001); + dP/dtmax: WMD = 1393.59 (95% CI = 972.57 to 1814.60, P < 0.001); -dP/dtmax: WMD = 850.06 (95% CI = 541.22 to 1158.90, P < 0.001); Left ventricular ejection fraction: WMD = 9.96 (95% CI = 7.29 to 12.63, P < 0.001)]. Apoptosis indicators [caspase-3: standardized mean difference (SMD) = 3.86 (95% CI = 2.97 to 4.76, P < 0.001); TUNEL-positive cells: WMD = 13.10 (95% CI = 8.15 to 18.05, P < 0.001)], inflammatory factor levels [TNF-α: SMD = 4.23 (95% CI = 2.48 to 5.98, P < 0.001)], oxidative stress indicators [Superoxide production: SMD = 4.53 (95% CI = 2.39 to 6.67, P < 0.001)], and lactate dehydrogenase levels [SMD = 2.82 (95% CI = 1.60 to 4.04, P < 0.001)] were significantly reduced. However, the superoxide dismutase content was significantly increased [SMD = 1.91 (95% CI = 1.17 to 2.65, P < 0.001)].
CONCLUSION
APN protects against MIRI via anti-inflammatory, antiapoptotic, and antioxidant effects, and this effect is achieved by activating different signaling pathways.
Topics: Rats; Animals; Myocardial Reperfusion Injury; Rats, Sprague-Dawley; Adiponectin; Myocardial Infarction; Signal Transduction; Apoptosis
PubMed: 38368320
DOI: 10.1186/s12944-024-02028-w -
Journal of Cardiovascular Development... Apr 2022Myocardial damage in acute myocardial infarctions (AMI) is primarily the result of ischemia−reperfusion injury (IRI). Recognizing the timing of transcriptional events... (Review)
Review
Myocardial damage in acute myocardial infarctions (AMI) is primarily the result of ischemia−reperfusion injury (IRI). Recognizing the timing of transcriptional events and their modulation by cardioprotective strategies is critical to address the pathophysiology of myocardial IRI. Despite the relevance of pigs for translational studies of AMI, only a few have identified how transcriptomic changes shape cellular signaling pathways in response to injury. We systematically reviewed transcriptomic studies of myocardial IRI and cardioprotection in Sus scrofa. Gene expression datasets were analyzed for significantly enriched terms using the Enrichr analysis tool, and statistically significant results (adjusted p-values of <0.05) for Signaling Pathways, Transcription Factors, Molecular Functions, and Biological Processes were compared between eligible studies to describe how these dynamic changes transform the myocardium from an injured and inflamed tissue into a scar. Then, we address how cardioprotective interventions distinctly modulate the myocardial transcriptome and discuss the implications of uncovering gene regulatory networks for cardiovascular pathologies and translational applications.
PubMed: 35621843
DOI: 10.3390/jcdd9050132 -
The Journal of Invasive Cardiology Nov 2014To correlate early and late mortality with markers of reperfusion in ST-elevation myocardial infarction (STEMI). (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To correlate early and late mortality with markers of reperfusion in ST-elevation myocardial infarction (STEMI).
BACKGROUND
Early reperfusion improves STEMI outcomes. Reperfusion can be assessed using angiographic (Thrombolysis in Myocardial Infarction [TIMI] flow grade or myocardial blush grade [MBG]) or electrocardiographic markers (ST-segment recovery (STR).
METHODS
We searched electronic databases for all STEMI randomized clinical studies from the last decade reporting markers of reperfusion and clinical outcome. We used a generalized estimating equation (GEE) model with logistic regression link in order to assess the correlation between each marker of reperfusion and mortality at 30 and 365 days. We also performed random effect meta-analysis for selected studies comparing mortality for specific categories of MBG.
RESULTS
We identified 44 studies with 19,955 patients. Final TIMI 3 flow was achieved in 87%, 70% had MBG 2 or 3, and 66% had complete STR. Average 30-day and 1-year mortality was 2.97 ± 2.34% and 4.11 ± 2.52%, respectively. Adjusting (study level) for age, diabetes, chronic kidney disease, infarct location, ejection fraction, and female sex, there was significant correlation between each of the three markers and 1-year mortality (P=.03 for TIMI 3; P=.02 for MBG 2 or 3; and P=.04 for STR). In nearly 6000 patients, there was substantial excess mortality in those with MBG 0/1 compared with MBG 2/3 (relative risk = 2.14 [1.65-2.77] with P<.001 at 30 days; relative risk = 1.49 [1.3-1.7] and P<.001 at 1 year).
CONCLUSION
After correcting for clinical factors known to affect outcome, there was a significant correlation between survival and better reperfusion.
Topics: Coronary Circulation; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Myocardial Infarction; Myocardial Reperfusion; Prognosis; Randomized Controlled Trials as Topic; Statistics as Topic; Stroke Volume; Survival Analysis; Thrombolytic Therapy
PubMed: 25364000
DOI: No ID Found -
Frontiers in Pharmacology 2022Phytoestrogens are a class of natural compounds that have structural similarities to estrogens. They have been identified to confer potent cardioprotective effects in...
Phytoestrogens are a class of natural compounds that have structural similarities to estrogens. They have been identified to confer potent cardioprotective effects in experimental myocardial ischemia-reperfusion injury (MIRI) animal models. We aimed to investigate the effect of PE on MIRI and its intrinsic mechanisms. A systematic search was conducted to identify PEs that have been validated in animal studies or clinical studies as effective against MIRI. Then, we collected studies that met inclusion and exclusion criteria from January 2016 to September 2021. The SYRCLE's RoB tool was used to evaluate the quality. Data were analyzed by STATA 16.0 software. The search yielded 18 phytoestrogens effective against heart disease. They are genistein, quercetin, biochanin A, formononetin, daidzein, kaempferol, icariin, puerarin, rutin, notoginsenoside R1, tanshinone IIA, ginsenoside Rb1, ginsenoside Rb3, ginsenoside Rg1, ginsenoside Re, resveratrol, polydatin, and bakuchiol. Then, a total of 20 studies from 17 articles with a total of 355 animals were included in this meta-analysis. The results show that PE significantly reduced the myocardial infarct size in MIRI animals compared with the control group ( < 0.001). PE treatment significantly reduced the creatine kinase level ( < 0.001) and cTnI level ( < 0.001), increased left ventricular ejection fraction ( < 0.001) and left ventricular fractional shortening ( < 0.001) in MIRI animals. In addition, PE also exerts a significant heart rate lowering effect ( < 0.001). Preclinical evidence suggests that PE can be multi-targeted for cardioprotective effects in MIRI. More large animal studies and clinical research are still needed in the future to further confirm its role in MIRI.
PubMed: 35668938
DOI: 10.3389/fphar.2022.847748 -
Oxidative Medicine and Cellular... 2022We conducted a meta-analysis to quantitatively evaluate the effect of melatonin therapy on patients with myocardial ischemia-reperfusion injury (MIRI) and explore the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We conducted a meta-analysis to quantitatively evaluate the effect of melatonin therapy on patients with myocardial ischemia-reperfusion injury (MIRI) and explore the influencing factors.
BACKGROUND
Although preclinical studies have shown that melatonin can alleviate MIRI, its protective effect on MIRI in patients remains controversial.
METHODS
We searched PubMed, the Cochrane Library, and Embase. The primary outcome was cardiac function (left ventricular ejection fraction [LVEF], left ventricular end-diastolic volume [LVEDV], and left ventricular end-systolic volume [LVESV]) and myocardial infarct parameters (total left ventricular mass and infarct size).
RESULTS
We included nine randomized controlled clinical trials with 631 subjects. Our results showed that melatonin had no significant effects on the primary outcome, but subgroup analyses indicated that when melatonin was administered by intravenous and intracoronary injection at the early stage of myocardial ischemia, LVEF was improved (<3.5 h; standardized mean difference [SMD]:0.50; 95% CI: 0.06 to 0.94; = 0.03) and the infarct size was reduced (<2.5 h, SMD: -0.86; 95% CI: -1.51 to -0.22; = 0.01), whereas when melatonin was injected at the late stage of myocardial ischemia (≥3.5 h or 2.5 h), the results were the opposite. Furthermore, melatonin intervention reduced the level of cardiac injury markers, inflammatory cytokines, oxidation factors, and increased the level of antioxidant factors ( < 0.001).
CONCLUSIONS
The results indicated that the cardioprotective function of melatonin for MIRI was influenced by the route and timing regimen of melatonin administration; the mechanism of which may be associated with the production of inflammatory cytokines, the balance of oxidation, and antioxidant factors.
Topics: Antioxidants; Female; Humans; Male; Melatonin; Middle Aged; Myocardial Reperfusion Injury
PubMed: 35281465
DOI: 10.1155/2022/4610522 -
Free Radical Biology & Medicine Aug 2021Although myocardial ischemia-reperfusion injury (I/R) and its pathological consequences are the leading cause of morbidity and mortality worldwide, cardioprotective... (Review)
Review
Systematic review and network analysis of microRNAs involved in cardioprotection against myocardial ischemia/reperfusion injury and infarction: Involvement of redox signalling.
Although myocardial ischemia-reperfusion injury (I/R) and its pathological consequences are the leading cause of morbidity and mortality worldwide, cardioprotective therapeutics are still not on the market. Oxidative stress, a major contributing factor to myocardial I/R, changes transcription of coding and non-coding RNAs, alters post-transcriptional modulations, and regulate protein function. MicroRNA (miRNA) expression can be altered by oxidative stress and microRNAs may also regulate cytoprotective mechanisms and exert cardioprotection againts I/R. Transcriptomic analysis of I/R and oxidative stress-induced alterations followed by microRNA-mRNA target interaction network analysis may reveal microRNAs and their mRNA targets that may play a role in cardioprotection and serve as microRNA therapeutics or novel molecular targets for further drug development. Here we provide a summary of a systematic literature review and in silico molecular network analysis to reveal important cardioprotective microRNAs and their molecular targets that may provide cardioprotection via regulation of redox signalling.
Topics: Humans; Infarction; MicroRNAs; Myocardial Reperfusion Injury; Oxidation-Reduction; Signal Transduction
PubMed: 33965565
DOI: 10.1016/j.freeradbiomed.2021.04.034 -
Frontiers in Physiology 2018Astragaloside IV (AS-IV), the major pharmacological extract from , possesses a variety of biological activities in the cardiovascular systems. Here, we aimed to evaluate...
Astragaloside IV (AS-IV), the major pharmacological extract from , possesses a variety of biological activities in the cardiovascular systems. Here, we aimed to evaluate preclinical evidence and possible mechanism of AS-IV for animal models of myocardial ischemia/reperfusion (I/R) injury. Studies of AS-IV in animal models with myocardial I/R injury were identified from 6 databases from inception to May, 2018. The methodological quality was assessed by using CAMARADES 10-item checklist. All the data were analyzed using Rev-Man 5.3 software. As a result, 22 studies with 484 animals were identified. The quality score of studies ranged from 3 to 6 points. Meta-analyses showed AS-IV can significantly decrease the myocardial infarct size and left ventricular ejection fraction, and increase shortening fraction compared with control group ( < 0.01). Significant decreasing of cardiac enzymes and cardiac troponin and increasing of decline degree in ST-segment were reported in one study each ( < 0.05). Additionally, the possible mechanisms of AS-IV for myocardial I/R injury are promoting angiogenesis, improving the circulation, antioxidant, anti-inflammatory and anti-apoptosis. Thus, AS-IV is a potential cardioprotective candidate for further clinical trials of myocardial infarction.
PubMed: 30018562
DOI: 10.3389/fphys.2018.00795