Pyroptosis inhibition improves the symptom of acute myocardial infarction.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu W
PROVIDER: S-EPMC8445977 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The recovery from acute myocardial infarction (AMI) is influenced by physiological and psychological factors. While the physiological effects have been extensively studied, the contribution of psychological factors and whether they can be modulated is not completely clear. Here we show that the activity of the reward system, a brain network involved in motivation and positive expectation, affects outcomes in mice following AMI. We found that chemogenetic activation of dopaminergic neurons in the ventral tegmental area (VTA) significantly attenuated the remodeling process following AMI, resulting in improved left-ventricular performance compared to controls. VTA activation was associated with modulation of the immune response following AMI and increased blood vessel formation in the damaged area, mediated, at least in part, by changes in liver-secreted proteins. Together, our findings reveal a potential mechanism by which specific brain activity can affect the multifactorial systemic and local tissue response to AMI, introducing a novel target for therapeutic interventions
2024-05-03 | PXD043448 | Pride
Project description:BackgroundThe diagnosis of acute myocardial infarction (AMI) is missed more frequently in young women than men, which may be related to the cognitive psychology of the diagnostic process. Physicians start the diagnostic process by intuitively recognizing familiar symptom phenotypes, but little is known about how symptoms combine in individuals as unique symptom phenotypes. We examined how symptoms of AMI combine as unique symptom phenotypes in individual patients to compare the distribution of symptom phenotypes in women versus men.Methods and resultsThe VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) was a multicenter, observational cohort study of 3501 young adults hospitalized with AMI. Data were collected on presenting symptoms with standardized interviews and from medical record abstraction. The number and distribution of unique symptom phenotypes were compared between women and men. Because of the 2:1 female-to-male enrollment ratio, women and men were compared with permutation testing and repeated subsampling. There were 426 interview-symptom phenotypes in women and 280 in men. The observed difference between women and men of 146 phenotypes was significant, even allowing for the greater enrollment of women (permutation P=0.004, median difference 110 under the null hypothesis of no association between sex and phenotype). The repeated subsample analysis also showed significantly more interview-symptom phenotypes in women than men (206.8±7.3 versus 188.6±6.0, P<0.001). Women were more broadly distributed among symptom phenotype subgroups than men (P<0.001). Similar findings were observed in the analysis of symptoms abstracted from the medical record.ConclusionsWomen exhibited substantially more variation in unique symptom phenotypes than men, regardless of whether the symptoms were derived from structured interviews or abstracted from the medical record. These findings may provide an explanation for the higher missed diagnosis rate in young women with AMI and may have important implications for teaching and improving clinicians' ability to recognize the diagnosis of AMI in women.
| S-EPMC7041412 | biostudies-literature
Project description:Podoplanin, a small mucine-type transmembrane glycoprotein, has been recently shown to be expressed by lymphangiogenic, fibrogenic and mesenchymal progenitor cells in the acutely and chronically infarcted myocardium. Podoplanin binds to CLEC-2, a C-type lectin-like receptor 2 highly expressed by CD11bhigh cells following inflammatory stimuli. Why podoplanin expression appears only after organ injury is currently unknown. Here, we characterize the role of podoplanin in different stages of myocardial repair after infarction and propose a podoplanin-mediated mechanism in the resolution of post-MI inflammatory response and cardiac repair. Neutralization of podoplanin led to significant improvements in the left ventricular functions and scar composition in animals treated with podoplanin neutralizing antibody. The inhibition of the interaction between podoplanin and CLEC-2 expressing immune cells in the heart enhances the cardiac performance, regeneration and angiogenesis post MI. Our data indicates that modulating the interaction between podoplanin positive cells with the immune cells after myocardial infarction positively affects immune cell recruitment and may represent a novel therapeutic target to augment post-MI cardiac repair, regeneration and function.
| S-EPMC6693826 | biostudies-other
Project description:BackgroundPrompt recognition of acute myocardial infarction symptoms and timely care-seeking behavior are critical to optimize acute medical therapies. Relatively little is known about the symptom presentation and care-seeking experiences of women aged ≤55 years with acute myocardial infarction, a group shown to have increased mortality risk as compared with similarly aged men. Understanding symptom recognition and experiences engaging the healthcare system may provide opportunities to reduce delays and improve acute care for this population.Methods and resultsWe conducted a qualitative study using in-depth interviews with 30 women (aged 30-55 years) hospitalized with acute myocardial infarction to explore their experiences with prodromal symptoms and their decision-making process to seek medical care. Five themes characterized their experiences: (1) prodromal symptoms varied substantially in both nature and duration; (2) they inaccurately assessed personal risk of heart disease and commonly attributed symptoms to noncardiac causes; (3) competing and conflicting priorities influenced decisions about seeking acute care; (4) the healthcare system was not consistently responsive to them, resulting in delays in workup and diagnosis; and (5) they did not routinely access primary care, including preventive care for heart disease.ConclusionsParticipants did not accurately assess their cardiovascular risk, reported poor preventive health behaviors, and delayed seeking care for symptoms, suggesting that differences in both prevention and acute care may be contributing to young women's elevated acute myocardial infarction mortality relative to men. Identifying factors that promote better cardiovascular knowledge, improved preventive health care, and prompt care-seeking behaviors represent important target for this population.
| S-EPMC4801001 | biostudies-literature
Project description:PF-1355 is an oral myeloperoxidase (MPO) inhibitor that successfully decreased elevated MPO activity in mouse myocardial infarction models. Short duration PF-1355 treatment for 7 days decreased the number of inflammatory cells and attenuated left ventricular dilation. Cardiac function and remodeling improved when treatment was increased to 21 days. Better therapeutic effect was further achieved with early compared with delayed treatment initiation (1 h vs. 24 h after infarction). In conclusion, PF-1355 treatment protected a mouse heart from acute and chronic effects of MI, and this study paves the way for future translational studies investigating this class of drugs in cardiovascular diseases.
| S-EPMC6113523 | biostudies-literature
Project description:BackgroundDiabetes is frequently associated with poor prognosis among acute myocardial infarction (AMI) patients. Patients with these comorbidities often have atypical symptoms and subsequent delay in treatment. Few studies have reported detailed AMI symptoms in patients with diabetes. This study compared AMI symptoms and presentation characteristics between diabetics and non-diabetics.MethodsWe included patients from the China AMI registry diagnosed with AMI between January 2013 and September 2014. Baseline characteristics, symptomology, and delay in treatment were compared between diabetics and non-diabetics. Multivariable logistic regression analysis was used to explore independent predictors of atypical symptoms.ResultsA total of 4450 (20.2%) patients had diabetes. They were older, more often women, higher in body mass index, and more likely to have non-ST segment elevation myocardial infarction. Fewer diabetic patients presented with persistent precordial chest pain (63.1% vs. 68%, P < 0.0001), diaphoresis (60.1% vs. 65.6%, P < 0.0001), fatigue (16.7% vs. 18.3%, P = 0.0123), and incontinence (0.4% vs. 0.7%, P = 0.0093). Time to hospital presentation was longer among patients with diabetes than those without. In multivariable analysis, diabetes was identified as an independent predictor of atypical symptoms (OR: 1.112, 95% CI: 1.034-1.196).ConclusionsOur study is the first large-scale study providing evidence that diabetics are less likely to present with typical chest pain and more likely to experience treatment delay when suffering from an AMI. Our results may increase clinician awareness of recognizing AMI patients rapidly to reduce diagnosis and treatment delay, particularly in the context of diabetes.
| S-EPMC6558571 | biostudies-literature
Project description:BackgroundPreclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans.Methods and resultsOverall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (≤30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P<0.0001) and plasma C-reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P=0.0005) despite having similar aortic (P=0.12) and less coronary (P=0.006) atherosclerotic burden and similar paraspinal muscular 18F-fluorodeoxyglucose uptake (P=0.52). Patients with ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to >50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P=0.03) than those with non-ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI.ConclusionsThe presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01749254.
| S-EPMC4599491 | biostudies-literature
Project description:Acute myocardial infarction (AMI) induces blood leukocytosis, which correlates inversely with patient survival. The molecular mechanisms leading to leukocytosis in the infarcted heart remain poorly understood. Using an AMI mouse model, we identified gasdermin D (GSDMD) in activated leukocytes early in AMI. We demonstrated that GSDMD is required for enhanced early mobilization of neutrophils to the infarcted heart. Loss of GSDMD resulted in attenuated IL-1β release from neutrophils and subsequent decreased neutrophils and monocytes in the infarcted heart. Knockout of GSDMD in mice significantly reduced infarct size, improved cardiac function, and increased post-AMI survival. Through a series of bone marrow transplantation studies and leukocyte depletion experiments, we further clarified that excessive bone marrow-derived and GSDMD-dependent early neutrophil production and mobilization (24 hours after AMI) contributed to the detrimental immunopathology after AMI. Pharmacological inhibition of GSDMD also conferred cardioprotection after AMI through a reduction in scar size and enhancement of heart function. Our study provides mechanistic insights into molecular regulation of neutrophil generation and mobilization after AMI, and supports GSDMD as a new target for improved ventricular remodeling and reduced heart failure after AMI.
| S-EPMC8718151 | biostudies-literature
Project description:Acute myocardial infarction (AMI) induces blood leukocytosis, which correlates inversely with patient survival. The molecular mechanisms leading to leukocytosis, and recruitment to the infarcted heart, remain poorly understood. Using an AMI mouse model, gasdermin D (GSDMD) was identified in activated neutrophils early in AMI. We demonstrated that GSDMD is required for enhanced recruitment of neutrophils and monocytes to the infarcted heart. Loss of GSDMD resulted in reduced release of IL-1β from neutrophils and reduced recruitment of neutrophils and monocytes to the infarcted heart. Knockout of GSDMD in mice significantly reduced infarct size, improved cardiac function and increased survival post AMI. Through a series of bone marrow transplantation studies and leukocytes depletion experiments, we further demonstrated that excessive bone marrow derived and GSDMD-dependent neutrophil recruitment, contributes to the detrimental immunopathology after AMI. Pharmacological inhibition of GSDMD also conferred cardioprotection post AMI, through reduction of scar size and enhancement of heart function. Our study provides new mechanistic insights into molecular regulation of neutrophil generation and recruitment after AMI, and supports GSDMD as a new target for improved ventricular remodeling and reduced heart failure after AMI.
2022-01-05 | GSE181872 | GEO
Project description:Background Since the knowledge of the symptoms of acute myocardial infarction (AMI) may reduce the decision time for patients to seek help in case of an AMI, we aimed to summarize evidence on the knowledge of the AMI symptoms and the symptom attribution in case of an acute coronary syndrome (ACS). Methods Therefore, we systematically searched the databases PubMed, CINAHL, Embase, and Cochrane Library for relevant studies published between January 1, 2008 and 2019 (last search August 1, 2019). Results A total of 86 studies were included, with a composite sample size of 354,497 participants. The weighted mean of the knowledge scores for the symptoms of AMI of 14,420 participants from the general population, was 42.1% (when maximum score was considered 100%) and 69.5% for 7642 cardiac patients. There was a substantially better level of knowledge for six symptoms (‘chest pain or discomfort’, ‘shortness of breath’, ‘pain or discomfort in arms or shoulders’, ‘feeling weak, lightheaded, or faint’, ‘pain or discomfort in the jaw, neck, or back’, and ‘sweating’) (49.8–88.5%) compared to the four less obvious/atypical symptoms ‘stomach or abdominal discomfort’, ‘nausea or vomiting’, ‘headache’, and ‘feeling of anxiety’ (8.7–36.7%). Only 45.1% of 14,843 patients, who experienced ACS, have correctly attributed their symptoms to a cardiac cause. Conclusion In conclusion, we found a moderate to good knowledge of “classic” and insufficient knowledge of less obvious symptoms of AMI. This might suggest that increasing knowledge about less obvious symptoms of AMI could be beneficial. It appears also important to address cardiac attribution of symptoms.
| S-EPMC7557019 | biostudies-literature