Expression and clinical significance of NRLP1 in patients with ST-segment elevation myocardial infarction combined with malignant ventricular arrhythmia.

Objective: To investigate the clinical effects of NRLP1 expression in patients with ST-segment elevation myocardial infarction (STEMI) combined with arrhythmia. Methods: We enrolled 231 patients with STEMI in the first hospital of Quanzhou affiliated to Fujian Medical University from January 2019 to December 2020 to the observational group and 230 healthy individuals as the control group. We divided patients with STEMI into a malignant ventricular arrhythmia (MVA) group (n=36) and non-MVA(NMVA) group (n=195) depending on whether the individuals had experienced an episode of MVA within 48 hours after PCI. We recorded general variables such as age, gender, history of smoking, hypertension, of diabetes, hyperlipidemia, left ventricular ejection fraction (LVEF), Gensini score, and mortality. Moreover, we determined NLRP1, IL-1ß, TNF-α, high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), cardiac troponin-1 (cTnI), and creatine kinase isoenzyme (CK-MB) in peripheral blood by ELISA. Results: We found significant differences in LVEF, Gensini scores, smoking history, and mortality between the MVA and NMVA groups. The mean NLRP1 expression was highest in the MVA group, which was positively correlated with the levels of IL-1ß, TNF-α, hs-CRP, NT-pro-BNP, cTnI and CK-MB. The expression of NLRP1 was associated with the smoking history, the LVEF value, the Gensini score, the MVA incidence and the mortality. Patients with higher NLRP1 expression levels had a higher MACE incidence and worse overall survivals within one year. Conclusion: The NLRP1 pathway is associated with the presence of arrhythmias after PCI treatments, and the NLRP1 expression level may be useful as a predictor of arrhythmia in patients with STEMI.

The relationship between dyslipidemia and inflammation among adults in east coast China: A cross-sectional study.

Objective: Dyslipidemia is one of the major public health problems in China. It is characterized by multisystem dysregulation and inflammation, and oxidant/antioxidant balance has been suggested as an important factor for its initiation and progression. The objective of this study was to determine the relationship between prevalence of dyslipidemia and measured changes in the levels of proinflammatory cytokines (IL-6, TNF-a, and MCP-1), thiobarbituric acid-reactant substances (TBARS), and serum total antioxidant capacity (TAC) in serum samples. Study design: A cross-sectional survey with a purposive sampling of 2,631 enrolled participants (age 18-85 years) was performed using the adult population of long-term residents of the municipality of east coast China in Fujian province between the years 2017 and 2019. Information on general health status, dyslipidemia prevalence, and selected mediators of inflammation was collected through a two-stage probability sampling design according to socioeconomic level, sex, and age. Methods: The lipid profile was conducted by measuring the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) with an autoanalyzer. Dyslipidemia was defined according to National Cholesterol Education Program Adult Treatment Panel III diagnostic criteria, and patients with it were identified by means of a computerized database. Serum parameters including IL-6/TNF-a/MCP-1, TBARS, and TAC were measured in three consecutive years. Familial history, education level, risk factors, etc. were determined. The association between dyslipidemia and serum parameters was explored using multivariable logistic regression models. Sociodemographic, age, and risk factors were also investigated among all participants. Results: The mean prevalence of various dyslipidemia in the population at baseline (2017) was as follows: dyslipidemias, 28.50%; hypercholesterolemia, 26.33%; high LDL-C, 26.10%; low HDL-C, 24.44%; and hypertriglyceridemia, 27.77%. A significant effect of aging was found among all male and female participants. The mean levels of serum Il-6/TNF-a/MCP-1 were significantly higher in all the types of dyslipidemia among male participants. Female participants with all types of dyslipidemia but low HDL-C showed an elevation of IL-6 and MCP-1 levels, and those with dyslipidemias and hypercholesterolemia presented higher levels of TNF-a compared to the normal participants. The oxidative stress marker TBARS increased among all types of dyslipidemia except hypertriglyceridemia. All participants with different types of dyslipidemia had a lower total antioxidant capacity. Correlation analysis showed that cytokines and TBARS were positively associated with age, obesity, and diabetes mellitus, but not sex, sedentary leisure lifestyle, hypertension, and CVD/CHD history. The activity of TAC was negatively associated with the above parameters. Conclusions: The correlation between the prevalence of dyslipidemia and the modification of inflammation status was statistically significant. The levels of proinflammatory cytokines, oxidative stress, and antioxidant capacity in serum may reflect the severity of the lipid abnormalities. These promising results further warrant a thorough medical screening in enhanced anti-inflammatory and reduced oxidative stress to better diagnose and comprehensively treat dyslipidemia at an early stage.

Agomelatine prevents angiotensin II-induced endothelial and mononuclear cell adhesion.

Agomelatine is a non-selective melatonin receptor agonist and an atypical antidepressant with anti-inflammatory, neuroprotective, and cardioprotective effects. The renin-angiotensin system modulates blood pressure and vascular homeostasis. Angiotensin II (Ang II) and its receptor Ang II type I receptor (AT1R) are recognized as contributors to the pathogenesis of cardiovascular and cardiometabolic diseases, including diabetes, obesity, and atherosclerosis. The recruitment and attachment of monocytes to the vascular endothelium is a major event in the early stages of atherosclerosis and other cardiovascular diseases. In the present study, we demonstrate that agomelatine reduced Ang II-induced expression of AT1R while significantly inhibiting the attachment of monocytes to endothelial cells induced by Ang II and mediated by ICAM-1 and VCAM-1. Additionally, Ang II inhibited the expression of the chemokines CXCL1, MCP-1, and CCL5, which are critical in the process of immune cell recruitment and invasion. Agomelatine also suppressed the expression of TNF-α, IL-8, and IL-12, which are proinflammatory cytokines that promote endothelial dysfunction and atherogenesis. Importantly, we demonstrate that the inhibitory effect of agomelatine against the expression of adhesion molecules is mediated through the downregulation of Egr-1 signaling. Together, our findings provide evidence of a novel mechanism of agomelatine that may be practicable in the treatment and prevention of cardiovascular diseases.