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Pyroptosis inhibition improves the symptom of acute myocardial infarction.

ABSTRACT: Acute myocardial infarction (AMI), the leading cause of mortality worldwide, is a rapidly developing and irreversible disease. Therefore, proper prompt intervention at the early stage of AMI is crucial for its treatment. However, the molecular features in the early stage have not been clarified. Here, we constructed mouse AMI model and profiled transcriptomes and proteomes at the early stages of AMI progress. Immune system was extensively activated at 6-h AMI. Then, pyroptosis was activated at 24-h AMI. VX-765 treatment, a pyroptosis inhibitor, significantly reduced the infarct size and improved the function of cardiomyocytes. Besides, we identified that WIPI1, specifically expressed in heart, was significantly upregulated at 1 h after AMI. Moreover, WIPI1 expression is significantly higher in the peripheral blood of patients with AMI than healthy control. WIPI1 can serve as a potential early diagnostic biomarker for AMI. It likely decelerates AMI progress by activating autophagy pathways. These findings shed new light on gene expression dynamics in AMI progress, and present a potential early diagnostic marker and a candidate drug for clinical pre-treatment to prolong the optimal cure time.

SUBMITTER: Liu W

PROVIDER: S-EPMC8445977 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Pyroptosis inhibition improves the symptom of acute myocardial infarction.

Liu Wenju W Shen Junwei J Shen Junwei J Li Yanfei Y Wu Jiawen J Luo Xiaoli X Yu Yuanyuan Y Zhang Yuhan Y Gu Liang L Zhang Xiaobai X Jiang Cizhong C Li Jue J

Cell death & disease 20210916 10

Acute myocardial infarction (AMI), the leading cause of mortality worldwide, is a rapidly developing and irreversible disease. Therefore, proper prompt intervention at the early stage of AMI is crucial for its treatment. However, the molecular features in the early stage have not been clarified. Here, we constructed mouse AMI model and profiled transcriptomes and proteomes at the early stages of AMI progress. Immune system was extensively activated at 6-h AMI. Then, pyroptosis was activated at 2 ...[more]

PMID: 34531373

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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.

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.

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Pyroptosis inhibition improves the symptom of acute myocardial infarction.

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Pyroptosis inhibition improves the symptom of acute myocardial infarction.

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