Humans ; Myocarditis/diagnostic imaging* ; Magnetic Resonance Imaging ; Myocardium ; Giant Cells

Humans ; Myocarditis/diagnostic imaging* ; Magnetic Resonance Imaging ; Myocardium ; Giant Cells

OBJECTIVE: To observe the effects of electroacupuncture (EA) on cardiac function and local field potential (LFP) in sensory and motor cortices in mice with stress cardiomyopathy (SC), and to explore the possible mechanism of EA in improving SC. METHODS: Twenty-seven female C57BL/6 mice were randomized into a blank group, a model group and an EA group, 9 mice in each group. In the model group and the EA group, SC model was established by continuous intraperitoneal injection of isoproterenol (ISO) for 14 days. At the same time of modeling, EA was applied at "Neiguan" (PC 6) and "Shenmen" (HT 7) in the EA group, with disperse-dense wave, in frequency of 2 Hz/15 Hz, 15 min each time, once a day for 14 days. After intervention, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test within 5 minutes were observed; the left ventricular function indexes (left ventricular diameter of end-diastole [LVIDd], left ventricular diameter of end-systole [LVIDs], left ventricular volume of end-diastole [LVEDV], left ventricular volume of end-systole [LVESV], ejection fraction [EF] and fraction shortening [FS]) were detected by echocardiography; the changes in ST-segment amplitude and PR interval of electrocardiogram were observed; the morphology of myocardial tissue was observed by HE staining; the serum levels of cortisol (CORT), cardiac troponin T (cTnT) and brain natriuretic peptide (BNP) were detected by ELISA; the changes of LFP in sensory and motor cortices were recorded by Plexon multi-channel acquisition system. RESULTS: Compared with the blank group, in the model group, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test were decreased (P<0.05); LVIDd, LVIDs, LVEDV and LVESV were increased (P<0.05), EF and FS were decreased (P<0.05); ST-segment amplitude was increased (P<0.05) and PR interval was prolonged (P<0.05); irregular myocardial fiber arrangement, interstitial edema and inflammatory cell infiltration were observed; the serum levels of CORT, cTnT and BNP were increased (P<0.05); in the sensory cortex, the ratios of delta, theta, alpha and beta frequency bands were increased (P<0.05), the maximum energy spectrum of theta and beta frequency bands was increased (P<0.05), the power spectral density (PSD) of delta, theta, alpha, beta and gamma frequency bands was increased (P<0.05); in the motor cortex, the ratios of delta, theta, alpha and beta frequency bands were increased (P<0.05), the maximum energy spectrum as well as PSD of delta, theta, alpha, beta and gamma frequency bands were increased (P<0.05). Compared with model group, in the EA group, the total movement distance, the number of crossing grid and the number of crossing central grid of open field test were increased (P<0.05); LVIDd, LVIDs, LVEDV and LVESV were decreased (P<0.05), EF and FS were increased (P<0.05); ST-segment amplitude was decreased (P<0.05), and the PR interval was shortened (P<0.05); myocardial fiber injury and inflammatory cell infiltration were reduced; the serum levels of CORT, cTnT and BNP were decreased (P<0.05); in the sensory cortex, the ratios of theta, alpha and beta frequency bands were decreased (P<0.05), the ratio of gamma frequency band was increased (P<0.05), the maximum energy spectrum of theta frequency band as well as the PSD of theta, alpha, beta and gamma frequency bands were decreased (P<0.05); in the motor cortex, the ratios of theta, alpha and beta frequency bands were decreased (P<0.05) and the ratio of gamma frequency band was increased (P<0.05), the maximum energy spectrum of delta frequency band was increased (P<0.05), the maximum energy spectrum of theta frequency band as well as the PSD of theta and gamma frequency bands were decreased (P<0.05). CONCLUSION EA can improve cardiac function in mice with stress cardiomyopathy, and its mechanism may be related to the regulation of local field potentials in sensory and motor cortices.
Female ; Mice ; Animals ; Electroacupuncture ; Takotsubo Cardiomyopathy ; Motor Cortex ; Mice, Inbred C57BL ; Myocardium

Humans ; Muscular Dystrophy, Duchenne/epidemiology* ; Prevalence ; Myocardium

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Angiotensin II/pharmacology* ; Fibroblasts ; Mice, Inbred C57BL ; Fibrosis ; Collagen/pharmacology* ; Collagen Type I/metabolism* ; RNA, Messenger/metabolism* ; Myocardium/pathology*

Objective: To define differentially expressed N6-adenylate methylation (m6A) genes in the myocardial tissue of mice with myocardial infarction (MI) and explore its potential impact on the pathological process of MI. Methods: The random number table method was used to divide the eighteen SPF C57BL/6J male mice aged from 8 to 10 weeks into MI group (MI group, n=9) and control group (control group, n=9). Modified m6A genes from the myocardial tissue were detected via methylated RNA immunoprecipitation with the next generation sequencing (MeRIP-seq). We explored methylation modified characteristics, verified mRNA expression and m6A modified level by bioinformatics analysis, qPCR and MeRIP-qPCR. Results: The Heatmap revealed that 901 differentially modified m6A genes between MI and control group, of which 537 genes were upregulated, and 364 genes were downregulated. The principal component analysis affirmed that two groups could be distinguished significantly in terms of m6A gene modification. The characteristic sequence of m6A modification was GGACU and mainly concentrated in the coding sequence. According to the conjoint analysis with RNA-seq and MeRIP-seq, 119 genes expressed simultaneous m6A modification difference and mRNA expression difference. The Venn diagram exhibited the positive and negative correlation between m6A modification and mRNA expression. Besides, the GO enrichment analysis indicated that the genes with m6A differential modification in MI group were mainly involved in heart development and other processes. qPCR verified that Gbp6 was up-regulated, while Dnaja1 and Dnajb1 were down-regulated. MeRIP-qPCR revealed that the m6A modification level of Hspa1b was downregulated. Conclusion: Myocardial infarction induces differential modification of m6A in the mice model. In addition, the genes with m6A modification may be affected by methylation related enzymes, thus participating the pathogenesis of MI by regulating apoptosis and inflammation.
Male ; Animals ; Mice ; Mice, Inbred C57BL ; Methylation ; Myocardial Infarction/genetics* ; Myocardium ; RNA, Messenger/genetics* ; HSP40 Heat-Shock Proteins

Humans ; Cardiomyopathies ; Myocardium ; Ventricular Dysfunction, Left ; Ventricular Function, Left ; Stroke Volume

While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), the underlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, including heart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment by periodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate the relationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes (NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagy inhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. This study also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomal sensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity than gingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wild-type P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-type P.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which are virulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms the strong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.
Mice ; Rats ; Animals ; Porphyromonas gingivalis ; Gingipain Cysteine Endopeptidases ; Autophagosomes ; Myocardium ; Periodontal Diseases ; Heart Rupture

Heart failure with preserved ejection fraction (HFpEF) displays normal or near-normal left ventricular ejection fraction, diastolic dysfunction, cardiac hypertrophy, and poor exercise capacity. Berberine, an isoquinoline alkaloid, possesses cardiovascular benefits. Adult male mice were assigned to chow or high-fat diet with L-NAME ("two-hit" model) for 15 weeks. Diastolic function was assessed using echocardiography and noninvasive Doppler technique. Myocardial morphology, mitochondrial ultrastructure, and cardiomyocyte mechanical properties were evaluated. Proteomics analysis, autophagic flux, and intracellular Ca²⁺ were also assessed in chow and HFpEF mice. The results show exercise intolerance and cardiac diastolic dysfunction in "two-hit"-induced HFpEF model, in which unfavorable geometric changes such as increased cell size, interstitial fibrosis, and mitochondrial swelling occurred in the myocardium. Diastolic dysfunction was indicated by the elevated E value, mitral E/A ratio, and E/e' ratio, decreased e' value and maximal velocity of re-lengthening (-dL/dt), and prolonged re-lengthening in HFpEF mice. The effects of these processes were alleviated by berberine. Moreover, berberine ameliorated autophagic flux, alleviated Drp1 mitochondrial localization, mitochondrial Ca²⁺ overload and fragmentation, and promoted intracellular Ca²⁺ reuptake into sarcoplasmic reticulum by regulating phospholamban and SERCA2a. Finally, berberine alleviated diastolic dysfunction in "two-hit" diet-induced HFpEF model possibly because of the promotion of autophagic flux, inhibition of mitochondrial fragmentation, and cytosolic Ca²⁺ overload.
Male ; Mice ; Animals ; Heart Failure/drug therapy* ; Stroke Volume/physiology* ; Ventricular Function, Left/physiology* ; Berberine/therapeutic use* ; Disease Models, Animal ; Mitochondrial Dynamics ; Myocardium ; Homeostasis

OBJECTIVE: To investigate the value of T2 mapping in the assessment of myocardial changes and prognosis in patients with acute ST segment elevation myocardial infarction (STEMI). METHODS: A retrospective study was conducted. A total of 30 patients with acute STEMI admitted to Tianjin First Central Hospital from January 2021 to March 2022 were enrolled as the experimental group. At the same time, 30 age- and sex-matched healthy volunteers and outpatients with non-specific chest pain with no abnormalities in cardiac magnetic resonance (CMR) examination were selected as the control group. CMR was performed within 2 weeks after the diagnosis of STEMI, as the initial reference. A plain CMR review was performed 6 months later (chronic myocardial infarction, CMI). Plain scanning includes film sequence (CINE), T2 weighted short tau inversion recovery (T2-STIR), native-T1 mapping, and T2 mapping. Enhanced scanning includes first-pass perfusion, late gadolinium enhancement (LGE), and post-contrast T1 mapping. Quantitative myocardial parameters were compared between the two groups, before and after STEMI myocardial infarction. The receiver operator characteristic curve (ROC curve) was used to evaluate the diagnostic efficacy of native-T1 before myocardial contrast enhancement and T2 values in differentiating STEMI and CMI after 6 months. RESULTS: There were no statistically significant differences in age, gender, heart rate and body mass index (BMI) between the two groups, which were comparable. The native-T1 value, T2 value and extracellular volume (ECV) were significantly higher than those in the control group [native-T1 value (ms): 1 434.5±165.3 vs. 1 237.0±102.5, T2 value (ms): 48.3±15.6 vs. 21.8±13.1, ECV: (39.6±13.8)% vs. (22.8±5.0)%, all P < 0.05]. In the experimental group, 12 patients were re-examined by plain CMR scan 6 months later. After 6 months, the high signal intensity on T2-STIR was still visible, but the range was smaller than that in the acute phase, and the native-T1 and T2 values were significantly lower than those in the acute phase [native-T1 value (ms): 1 271.0±26.9 vs. 1 434.5±165.3, T2 value (ms): 34.2±11.2 vs. 48.3±15.6, both P < 0.05]. ROC curve analysis showed that the area under the ROC curve (AUC) of native-T1 and T2 values in differentiating acute STEMI from CMI was 0.71 and 0.80, respectively. When native-T1 cut-off value was 1 316.0 ms, the specificity was 100% and the sensitivity was 53.3%; when T2 cut-off value was 46.7 ms, the specificity was 100% and the sensitivity was 73.8%. CONCLUSIONS The T2 mapping is a non-invasive method for the diagnosis of myocardial changes in patients with acute STEMI myocardial infarction, and can be used to to evaluate the clinical prognosis of patients.
Humans ; ST Elevation Myocardial Infarction/diagnosis* ; Contrast Media ; Prognosis ; Retrospective Studies ; Magnetic Resonance Imaging, Cine/methods* ; Gadolinium ; Myocardium/pathology* ; Myocardial Infarction ; Predictive Value of Tests