Downregulation of HMGB1 carried by macrophage-derived extracellular vesicles delays atherosclerotic plaque formation through Caspase-11-dependent macrophage pyroptosis.

BACKGROUND: Macrophage-derived extracellular vesicle (macrophage-EV) is highly studied for its regulatory role in atherosclerosis (AS). Our current study tried to elucidate the possible role of macrophage-EV loaded with small interfering RNA against high-mobility group box 1 (siHMGB1) affecting atherosclerotic plaque formation. METHODS: In silico analysis was performed to find critical factors in mouse atherosclerotic plaque formation. EVs secreted by RAW 264.7 cells were collected by ultracentrifugation and characterized, followed by the preparation of macrophage-EV-loaded siHMGB1 (macrophage-EV/siHMGB1). ApoE-/- mice were used to construct an AS mouse model by a high-fat diet, followed by injection of macrophage-EV/siHMGB1 to assess the in vivo effect of macrophage-EV/siHMGB1 on AS mice. RAW264.7 cells were subjected to ox-LDL, LPS or macrophage-EV/siHMGB1 for analyzing the in vitro effect of macrophage-EV/siHMGB1 on macrophage pyrophosis and inflammation. RESULTS: In silico analysis found that HMGB1 was closely related to the development of AS. Macrophage-EV/siHMGB could inhibit the release of HMGB1 from macrophages to outside cells, and the reduced HMGB1 release could inhibit foam cell formation. Besides, macrophage-EV/siHMGB also inhibited the LPS-induced Caspase-11 activation, thus inhibiting macrophage pyroptosis and preventing atherosclerotic plaque formation. CONCLUSION: Our results proved that macrophage-EV/siHMGB could inhibit foam cell formation and suppress macrophage pyroptosis, finally preventing atherosclerotic plaque formation in AS mice.

L1 cell adhesion molecule may be a protective molecule for atrial fibrillation in patients with valvular heart disease.

Background: Atrial fibrillation (AF) is the most prevalent sustained arrhythmia. L1 cell adhesion molecule (L1CAM) served as a crucial regulator of signaling pathways. This research sought to examine the clinical value and functions of soluble L1CAM in the serum of AF patients. Methods: In total, 118 patients (valvular heart disease patients [VHD, total: n = 93; AF: n = 47; sinus rhythm (SR): n = 46] and healthy controls [n = 25]) were recruited in this retrospective study. Plasma levels of L1CAM were detected by enzyme-linked immunosorbent assays. The Pearson's correlation approach, as applicable, was used for analyzing the correlations. The L1CAM was shown to independently serve as a risk indicator of AF in VHD after being analyzed by the multivariable logistic regression. To examine the specificity and sensitivity of AF, receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used. A nomogram was developed for the visualisation of the model. We further evaluate the prediction model for AF using calibration plot and decision curve analysis. Results: The plasma level of L1CAM was substantially decreased in AF patients as opposed to healthy control and SR patients (healthy control = 46.79 ± 12.55 pg/ml, SR = 32.86 ± 6.11 pg/ml, AF = 22.48 ± 5.39 pg/ml; SR vs. AF, P < 0.001; control vs. AF, P < 0.001). L1CAM was significantly and negatively correlated with LA and NT-proBNP (LA: r = -0.344, P = 0.002; NT-proBNP: r = -0.380, P = 0.001). Analyses using logistic regression showed a substantial correlation between L1CAM and AF in patients with VHD (For L1CAM, Model 1: OR = 0.704, 95%CI = 0.607-0.814, P < 0.001; Model 2: OR = 0.650, 95% CI = 0.529-0.798, P < 0.001; Model 3: OR = 0.650, 95% CI = 0.529-0.798, P < 0.001). ROC analysis showed that inclusion of L1CAM in the model significantly improved the ability of other clinical indicators to predict AF. The predictive model including L1CAM, LA, NT-proBNP and LVDd had excellent discrimination and a nomogram was developed. The model had good the calibration and clinical utility. Conclusion: L1CAM was shown to independently serve as a risk indicator for AF in VHD. In AF patients with VHD, the prognostic and predictive effectiveness of models incorporating L1CAM was satisfactory. Collectively, L1CAM may be a protective molecule for atrial fibrillation in patients with valvular heart disease.

Noncoding RNA in the Regulation of Acute Aortic Dissection: From Profile to Mechanism.

Aortic dissection is a life-threatening condition caused by a tear in the intimal layer of the aorta or bleeding within the aortic wall, resulting in the separation of the layers of the aortic wall. As Nienaber reported, aortic dissection is most common in people 65-75 years old and has an incidence of 35 cases per 100,000 people per year in this population. Many pathogenic factors are involved in aortic dissection, including hypertension, dyslipidemia, and abnormality of the aortic intima caused by genetic variation. However, with the development of gene sequencing and transgenic technology, genetic methods are being used for the diagnosis and treatment of diseases, including acute aortic dissection. Genetic research on acute aortic dissection began around 2006. Recently, research on acute aortic dissection has mainly focused on microRNA (miRNA). Studies have found that miRNA plays a critical regulatory role in the occurrence and development of acute aortic dissection. By regulating miRNA expression, acute aortic dissection can be prevented and treated.

Relationship of pulse pressure index and carotid intima-media thickness in hypertensive adults.

OBJECTIVE: To evaluate the relationship between pulse pressure index (PPI) and carotid intima-media thickness (CIMT). METHOD: Observational trial was design and 342 patients newly diagnosed as hypertension without anti-hypertensive therapy were enrolled. According to the cut-off value of CIMT, 342 participants were divided into normal (< 0.9mm) and increased CIMT groups (≥ 0.9mm). Baseline characteristics were compared, logistic regression analysis and receiver operating characteristic curve (ROC) were performed. RESULTS: Approximately 34.2% of participants (n = 117) were with CIMT ≥ 0.9 mm and participants in increased CIMT group were more elderly. Diastolic blood pressure was lower in increased CIMT group than normal group (79.3 ± 10.8 mm Hg versus 83.8 ± 9.4 mm Hg, p < 0.001), whereas pulse pressure (PP) (59.3 ± 20.2 mm Hg versus 53.6 ± 15.5 mm Hg, p = 0.004) and PPI (0.43 ± 0.09 versus 0.38 ± 0.08, p < 0.001) were significantly higher in increased CIMT group. CIMTs were 1.11 ± 0.11 mm and 0.76 ± 0.12 in increased group and normal group respectively (p < 0.001). After adjusted for the traditional risk factors, only PPI was found an independent determinant for CIMT increase, and the odd ratio was 1.644 (95% interval confidence 1.280-2.112, p < 0.001). The ROC evaluations showed that area under the curve for PP to predict CIMT increase was 0.591 ± 0.034, and PPI was 0.664 ± 0.033. PPI was more powerful than PP in discriminating CIMT increase (p = 0.006). CONCLUSION: PPI is a valuable parameter for the preliminary screening of hypertensive patients who have an increased risk of atherosclerosis.