-
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 -
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 -
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 -
Annals of Medicine 2023Cardiac sympathetic hyperinnervation after myocardial infarction (MI) is associated with arrhythmogenesis and sudden cardiac death. The characteristics of cardiac... (Review)
Review
BACKGROUND
Cardiac sympathetic hyperinnervation after myocardial infarction (MI) is associated with arrhythmogenesis and sudden cardiac death. The characteristics of cardiac sympathetic hyperinnervation remain underexposed.
OBJECTIVE
To provide a systematic review on cardiac sympathetic hyperinnervation after MI, taking into account: (1) definition, experimental model and quantification method and (2) location, amount and timing, in order to obtain an overview of current knowledge and to expose gaps in literature.
METHODS
References on cardiac sympathetic hyperinnervation were screened for inclusion. The included studies received a full-text review and quality appraisal. Relevant data on hyperinnervation were collected and qualitatively analysed.
RESULTS
Our literature search identified 60 eligible studies performed between 2000 and 2022. Cardiac hyperinnervation is generally defined as an increased sympathetic nerve density or increased number of nerves compared to another control group (100%). Studies were performed in a multitude of experimental models, but most commonly in male rats with permanent left anterior descending (LAD) artery ligation (male: 63%, rat: 68%, permanent ligation: 93%, LAD: 97%). Hyperinnervation seems to occur mainly in the borderzone. Quantification after MI was performed in regions of interest in µm/mm (41%) or in percentage of nerve fibres (46%) and the reported amount showed a great variation ranging from 439 to 126,718 µm/mm. Hyperinnervation seems to start from three days onwards to >3 months without an evident peak, although studies on structural evaluation over time and in the chronic phase were scarce.
CONCLUSIONS
Cardiac sympathetic hyperinnervation after MI occurs mainly in the borderzone from three days onwards and remains present at later timepoints, for at least 3 months. It is most commonly studied in male rats with permanent LAD ligation. The amount of hyperinnervation differs greatly between studies, possibly due to differential quantification methods. Further studies are required that evaluate cardiac sympathetic hyperinnervation over time and in the chronic phase, in transmural sections, in the female sex, and in MI with reperfusion.
Topics: Male; Female; Rats; Humans; Animals; Heart; Myocardial Infarction; Arrhythmias, Cardiac; Sympathetic Nervous System; Death, Sudden, Cardiac
PubMed: 38065671
DOI: 10.1080/07853890.2023.2283195 -
Diagnostics (Basel, Switzerland) Nov 2020The complement system has a significant role in myocardial ischemia/reperfusion injury, being responsible for cell lysis and amplification of inflammatory response. In... (Review)
Review
The complement system has a significant role in myocardial ischemia/reperfusion injury, being responsible for cell lysis and amplification of inflammatory response. In this context, several studies highlight that terminal complement complex C5b-9, also known as the membrane attack complex (MAC), is a significant contributor. The MAC functions were studied by many researchers analyzing the characteristics of its activation in myocardial infarction. Here, a systematic literature review was reported to evaluate the principal features, advantages, and limits (regarding the application) of complement components and MAC in post mortem settings to perform the diagnosis of myocardial ischemia/infarction. The review was performed according to specific inclusion and exclusion criteria, and a total of 26 studies were identified. Several methods studied MAC, and each study contributes to defining better how and when it affects the myocardial damage in ischemic/reperfusion injury. The articles were discussed, focusing on the specificity, sensibility, and post mortem stability of MAC as a marker of myocardial ischemia/infarction, supporting the usefulness in routine post mortem investigations.
PubMed: 33147886
DOI: 10.3390/diagnostics10110898 -
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 -
Oxidative Medicine and Cellular... 2017Ginseng is an important herbal drug that has been used worldwide for many years. Ginsenoside Rb1 (G-Rb1), the major pharmacological extract from ginseng, possesses a... (Review)
Review
Ginseng is an important herbal drug that has been used worldwide for many years. Ginsenoside Rb1 (G-Rb1), the major pharmacological extract from ginseng, possesses a variety of biological activities in the cardiovascular systems. Here, we conducted a preclinical systematic review to investigate the efficacy of G-Rb1 for animal models of myocardial ischemia/reperfusion injury and its possible mechanisms. Ten studies involving 211 animals were identified by searching 6 databases from inception to May 2017. The methodological quality was assessed by using the CAMARADES 10-item checklist. All the data were analyzed using RevMan 5.3 software. As a result, the score of study quality ranged from 3 to 7 points. Meta-analyses showed that G-Rb1 can significantly decrease the myocardial infarct size and cardiac enzymes (including lactate dehydrogenase, creatine kinase, and creatine kinase-MB) when compared with control group ( < 0.01). Significant decrease in cardiac troponin T and improvement in the degree of ST-segment depression were reported in one study ( < 0.05). Additionally, the possible mechanisms of G-Rb1 for myocardial infarction are antioxidant, anti-inflammatory, antiapoptosis, promoting angiogenesis and improving the circulation. Thus, G-Rb1 is a potential cardioprotective candidate for further clinical trials of myocardial infarction.
Topics: Animals; Disease Models, Animal; Female; Ginsenosides; Male; Myocardial Reperfusion Injury; Panax; Rats
PubMed: 29430282
DOI: 10.1155/2017/6313625 -
PloS One 2017Metformin improves cardiovascular prognosis in patients with diabetes mellitus, compared to alternative glucose-lowering drugs, despite similar glycemic control. Direct... (Meta-Analysis)
Meta-Analysis Review
Metformin improves cardiovascular prognosis in patients with diabetes mellitus, compared to alternative glucose-lowering drugs, despite similar glycemic control. Direct cardiovascular protective properties have therefore been proposed, and studied in preclinical models of myocardial infarction. We now aim to critically assess the quality and outcome of these studies. We present a systematic review, quality assessment and meta-analysis of the effect of metformin in animal studies of experimental myocardial infarction. Through a comprehensive search in Pubmed and EMBASE, we identified 27 studies, 11 reporting on ex vivo experiments and 18 reporting on in vivo experiments. The primary endpoint infarct size as percentage of area at risk was significantly reduced by metformin in vivo (MD -18.11[-24.09,-12.14]) and ex vivo (MD -18.70[-25.39, -12.02]). Metformin improved the secondary endpoints left ventricular ejection fraction (LVEF) and left ventricular end systolic diameter. A borderline significant effect on mortality was observed, and there was no overall effect on cardiac hypertrophy. Subgroup analyses could be performed for comorbidity and timing of treatment (infarct size and mortality) and species and duration of ischemia (LVEF), but none of these variables accounted for significant amounts of heterogeneity. Reporting of possible sources of bias was extremely poor, including randomization (reported in 63%), blinding (33%), and sample size calculation (0%). As a result, risk of bias (assessed using SYRCLE's risk of bias tool) was unclear in the vast majority of studies. We conclude that metformin limits infarct-size and improves cardiac function in animal models of myocardial infarction, but our confidence in the evidence is lowered by the unclear risk of bias and residual unexplained heterogeneity. We recommend an adequately powered, high quality confirmatory animal study to precede a randomized controlled trial of acute administration of metformin in patients undergoing reperfusion for acute myocardial infarction.
Topics: Animals; In Vitro Techniques; Metformin; Mice; Myocardial Infarction; Rabbits; Rats; Swine
PubMed: 28832637
DOI: 10.1371/journal.pone.0183664 -
Frontiers in Pharmacology 2023Tanshinone IIA (Tan IIA), the major active lipophilic ingredient of , exerts various therapeutic effects on the cardiovascular system. We aimed to identify the...
Tanshinone IIA (Tan IIA), the major active lipophilic ingredient of , exerts various therapeutic effects on the cardiovascular system. We aimed to identify the preclinical evidence and possible mechanisms of Tan IIA as a cardioprotective agent in the treatment of myocardial ischemia/reperfusion injury. The study quality scores of twenty-eight eligible studies and data analyses were separately assessed using the CAMARADES 10-item checklist and Rev-Man 5.3 software. The study quality score ranged from 3/10 to 7/10 points. The present study provided preliminary preclinical evidence that Tan IIA could significantly decrease the myocardial infarct size, cardiac enzyme activity and troponin levels compared with those in the control group (). Tan IIA alleviated myocardial I/R injury via antioxidant, anti-inflammatory, anti-apoptosis mechanisms and improved circulation and energy metabolism. Thus, Tan IIA is a promising cardioprotective agent for the treatment of myocardial ischemia/reperfusion injury and should be further investigated in clinical trials.
PubMed: 37261285
DOI: 10.3389/fphar.2023.1165212 -
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