The amino acid metabolomics signature of differentiating myocardial infarction from strangulation death in mice models.

This study differentiates myocardial infarction (MI) and strangulation death (STR) from the perspective of amino acid metabolism. In this study, MI mice model via subcutaneous injection of isoproterenol and STR mice model by neck strangulation were constructed, and were randomly divided into control (CON), STR, mild MI (MMI), and severe MI (SMI) groups. The metabolomics profiles were obtained by liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics. Principal component analysis, partial least squares-discriminant analysis, volcano plots, and heatmap were used for discrepancy metabolomics analysis. Pathway enrichment analysis was performed and the expression of proteins related to metabolomics was detected using immunohistochemical and western blot methods. Differential metabolites and metabolite pathways were screened. In addition, we found the expression of PPM1K was significantly reduced in the MI group, but the expression of p-mTOR and p-S6K1 were significantly increased (all P < 0.05), especially in the SMI group (P < 0.01). The expression of Cyt-C was significantly increased in each group compared with the CON group, especially in the STR group (all P < 0.01), and the expression of AMPKα1 was significantly increased in the STR group (all P < 0.01). Our study for the first time revealed significant differences in amino acid metabolism between STR and MI.

CCK1R2R-/- ameliorates myocardial damage caused by unpredictable stress via altering fatty acid metabolism.

The heart is the main organ of the circulatory system and requires fatty acids to maintain its activity. Stress is a contributor to aggravating cardiovascular diseases and even death, and exacerbates the abnormal lipid metabolism. The cardiac metabolism may be disturbed by stress. Cholecystokinin (CCK), which is a classical peptide hormone, and its receptor (CCKR) are expressed in myocardial cells and affect cardiovascular function. Nevertheless, under stress, the exact role of CCKR on cardiac function and cardiac metabolism is unknown and the mechanism is worth exploring. After unpredictable stress, a common stress-inducing model that induces the development of mood disorders such as anxiety and reduces motivated behavior, we found that the abnormal contraction and diastole of the heart, myocardial injury, oxidative stress and inflammation of mice were aggravated. Cholecystokinin A receptor and cholecystokinin B receptor knockout (CCK1R2R-/-) significantly reversed these changes. Mechanistically, fatty acid metabolism was found to be altered in CCK1R2R-/- mice. Differential metabolites, especially L-tryptophan, L-aspartic acid, cholesterol, taurocholic acid, ADP, oxoglutaric acid, arachidonic acid and 17-Hydroxyprogesterone, influenced cardiac function after CCK1R2R knockout and unpredictable stress. We conclude that CCK1R2R-/- ameliorated myocardial damage caused by unpredictable stress via altering fatty acid metabolism.

Abnormal fatty acid metabolism and ceramide expression may discriminate myocardial infarction from strangulation death: A pilot study.

Determining myocardial infarction (MI) and mechanical asphyxia (MA) was one of the most challenging tasks in forensic practice. The present study aimed to investigate the potential of fatty acid (FAs) metabolism, and lipid alterations in determining MI and MA. MA and MI mouse models were constructed, and metabolic profiles were obtained by LC-MS-based untargeted metabolomics. The metabolic alterations were explored using the PCA, OPLS-DA, the Wilcoxon test, and fold change analysis. The contents of lipid droplets (LDs) were detected by the transmission scanning electron microscope and Oil red O staining. The immunohistochemical assay was performed to detect CD36 and dysferlin. The ceramide was assessed by LC-MS. PCA showed considerable differences in the metabolite profiles, and the well-fitting OPLS-DA model was developed to screen differential metabolites. Thereinto, 9 metabolites in the MA were reduced, while metabolites were up- and down-regulated in MI. The increased CD36 suggested that MI and MA could enhance the intake of FAs and disturb energy metabolism. The increased LDs, decreased dysferlin, and increased ceramide (C18:0, C22:0, and C24:0) were observed in MI groups, confirming the lipid deposition. The present study indicated significant differences in myocardial FAs metabolism and lipid alterations between MI and MA, suggesting that FAs metabolism and related proteins, certain ceramide may harbor the potential as biomarkers for discrimination of MI and MA.

Research Progress and Forensic Application of Postmortem Genetic Testing in Hereditary Cardiac Diseases.

Hereditary cardiac disease accounts for a large proportion of sudden cardiac death (SCD) in young adults. Hereditary cardiac disease can be divided into hereditary structural heart disease and channelopathies. Hereditary structural heart disease mainly includes hereditary cardiomyopathy, which results in arhythmia, heart failure and SCD. The autopsy and histopathological examinations of SCD caused by channelopathies lack characteristic morphological manifestations. Therefore, how to determine the cause of death in the process of examination has become one of the urgent problems to be solved in forensic identification. Based on the review of recent domestic and foreign research results on channelopathies and hereditary cardiomyopathy, this paper systematically reviews the pathogenesis and molecular genetics of channelopathies and hereditary cardiomyopathy, and discusses the application of postmortem genetic testing in forensic identification, to provide reference for forensic pathology research and identification of SCD.

Case report: Myocarditis following COVID-19 protein subunit vaccination.

We report findings in a 34-year-old female patient who presented with fulminant myocarditis 8 days after receiving the first dose of the ZF2001 RBD-subunit vaccine against coronavirus disease 2019 (COVID-19). Autopsy showed severe interstitial myocarditis, including multiple patchy infiltrations of lymphocytes and monocytes in the myocardium of the left and right ventricular walls associated with myocyte degeneration and necrosis. This report highlights the details of clinical presentations and autopsy findings of myocarditis after ZF2001 (RBD-subunit vaccine) vaccination. The correlation between vaccination and death due to myocarditis is discussed.