Effect of inflammatory factors on myocardial infarction.

BACKGROUND: Cohort studies have increasingly shown associations between inflammatory markers and myocardial infarction (MI); however, the specific causal relationships between inflammatory markers and the development of MI remain unclear. METHODS AND RESULTS: By utilizing publicly accessible genome-wide association studies, we performed a two-sample Mendelian randomization (MR) analysis to explore the causal associations between inflammatory markers and myocardial infarction (MI). A random-effects inverse-variance weighted method was used to calculate effect estimates. The study included a total of 395,795 European participants for MI analysis and various sample sizes for inflammatory factors, ranging from 3,301 to 563,946 participants.Neutrophil count was found to increase the risk of MI (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.00-1.17; p = 0.04). C-reactive protein levels correlated positively with MI. No associations were observed with IL-1 beta, IL-6, IL-18, procalcitonin, TNF-α, total white cell count, or neutrophil percentage of white cells. Neutrophil count and C-reactive protein were inversely associated with lactate dehydrogenase: neutrophil cell count (OR 0.95; 95% CI, 0.93-0.98; p < 0.01) and C-reactive protein (OR 0.96; 95% CI, 0.92-1.00; p = 0.02). No associations of MI with myoglobin, troponin I, and creatine kinase-MB levels were found. CONCLUSIONS: This two-sample MR analysis revealed a causal positive association of MI with neutrophil count, C-reactive protein level, and the myocardial injury marker lactate dehydrogenase. These results indicate that monitoring C-reactive protein and neutrophil counts may be useful in management of MI patients.

The Increased TIGIT-Expressing CD3+CD56+ Cells Are Associated with Coronary Artery Disease and Its Inflammatory Environment.

We aimed to examine the correlation of T-cell immunoglobulin and ITIM domain (TIGIT)-expressing CD3 + CD56 + cells (TNKS) with coronary artery disease (CAD), atherosclerotic lesion progression, and inflammatory environment. A total of 199 subjects, including 98 patients with acute coronary syndrome (ACS), 52 patients with chronic coronary syndrome (CCS), and 49 control subjects, were recruited in the study. The TIGIT-expressing TNKS were quantified by flow cytometric analysis; the severity of coronary artery lesions was evaluated by the Gensini score. Whole blood cells were stimulated with interleukin-2 (IL-2), interleukin-7 (IL-7), and interleukin-15 (IL-15) in presence or absence of STAT, PI3K, and P38 MAPK inhibitors, respectively. The TIGIT-expressing TNKS was significantly increased in patients with CAD, ACS, and CCS compared to the control group (P < 0.05). The TIGIT-expressing TNKS were independent predictors of CAD, ACS and CCS (P < 0.05). The TIGIT-expressing TNKS were positively associated with Gensini score (P < 0.05). The TIGIT-expressing TNKS was positively correlated with age, and being male (P < 0.05). The inflammatory microenviroment with increased IL-2, IL-7, and IL-15 contributed to upregulation of TIGIT expression in TNKS. PI3K and P38 MAPK inhibitors could inhibit the upregulation of TIGIT expression in TNKS induced by IL-2, IL-7, and IL-15. The TIGIT-expressing TNKS may be involved in common pathogenesis of ACS and CCS, and atherosclerotic lesion progression. Meanwhile, the increased TIGIT-expressing TNKS might be associated with a proatherogenic microenvironment or inflammatory microenvironment. PI3K and P38 MAPK signaling pathways were involved in the regulation of TIGIT expression.

Correlation of apolipoprotein A-I with T cell subsets and interferon-Ò¯ in coronary artery disease.

BACKGROUND: The association of Apolipoprotein A-I (APOAI) with T cell subsets and interferon-ү (IFN-γ) in patients with coronary artery disease (CAD) has been not reported. Thus, this study aimed to investigate the association of APOAI with T cell subsets and IFN-γ in CAD. METHODS: This study included a total of 107 patients with CAD including acute coronary syndrome and chronic coronary syndrome. T cell subsets, and CD3-CD56+ natural killer cells were quantified by flow cytometric analysis. The serum concentrations of IFN-ү were measured by enzyme-linked immunosorbent assay. Lipid profiles, C-reactive protein (CRP), and fibrinogen were measured in the clinical laboratory. Clinical data was obtained duration hospitalization. RESULTS: The CD4+ T cells were higher in patients of the low-APOAI group ( .05). The high-density lipoprotein cholesterol (HDL-C) was also inversely associated with CD4+ T cells (p < .05), and positively associated with CD8+ T cells (p < .05). Lastly, APOA1 and HDL-C did not correlated with fibrinogen and CRP (p > .05). CONCLUSION: The present study demonstrated the correlation of APOAI with T cell subsets and IFN-γ in CAD. These results provided novel information for the regulatory action between APOAI and T cell subsets and inflammatory immunity in CAD.

PCSK9 Knockdown Can Improve Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy.

This study investigates the effect and mechanism of proprotein convertase subtilisin/Kexin type 9 (PCSK9) on myocardial ischemia-reperfusion injury (MIRI) and provides a reference for clinical prevention and treatment of acute myocardial infarction (AMI). We established a rat model of myocardial ischemia/reperfusion (I/R) and AC16 hypoxia/reoxygenation (H/R) model. A total of 48 adult 7-week-old male Sprague-Dawley rats were randomly assigned to three groups (n = 16): control, I/R, and I/R + SiRNA. In I/R and I/R + siRNA groups, myocardial ischemia was induced via occlusion of the left anterior descending branch (LAD) of the coronary artery in rats in I/R group for 30 min and reperfused for 3 days. To assess the myocardial injury, the rats were subjected to an electrocardiogram (ECG), cardiac function tests, cardiac enzymes analysis, and 2,3,5-triphenyl tetrazolium chloride (TTC)/Evan Blue (EB) staining. Meanwhile, differences in the expression of autophagy-level proteins and Bcl-2/adenovirus E1B 19-kDa interacting protein (Bnip3) signaling-related proteins were determined by protein blotting. In vitro and in vivo experimental studies revealed that siRNA knockdown of PCSK9 reduced the expression of autophagic protein Beclin-1, light chain 3 (LC3) compared to normal control-treated cells and control-operated groups. Simultaneously, the expression of Bnip3 pathway protein was downregulated. Furthermore, the PCSK9-mediated small interfering RNA (siRNA) group injected into the left ventricular wall significantly improved cardiac function and myocardial infarct size. In ischemic/hypoxic circumstances, PCSK9 expression was dramatically increased. PCSK9 knockdown alleviated MIRI via Bnip3-mediated autophagic pathway, inhibited inflammatory response, reduced myocardial infarct size, and protected cardiac function.

The relationship between soluble lymphocyte activation gene-3 and coronary artery disease.

Background: Soluble lymphocyte activation gene 3 (sLAG3) may be used for diagnosis or prognosis in various diseases. However, the relationship between sLAG3 and coronary artery disease (CAD) are still unclear. This study aimed to investigate the levels of sLAG3 in patients with CAD, and its potential clinical association with the disease. Methods: A total of 66 subjects (49 patients with CAD and 17 control subjects without CAD) were enrolled. The sLAG3 level was measured using enzyme-linked immunosorbent assay (ELISA) kits. Clinical variables included demographics, biochemical markers, coronary angiography status, and ejection fraction of the heart (EF) were collected, and Gensini scores were calculated. LAG3 gene data was extracted from three datasets (GSE23561, GSE61144, GSE60993) in Gene Expression Omnibus (GEO) to compare differential expression between CAD and control subjects. Results: The sLAG3 level was significantly lower in the CAD vs. the controls (P < 0.05), and negatively associated with CAD [odds ratio (OR): 0.212, 95% confidential interval (CI): 0.060-0.746, P < 0.05]. Furthermore, the area under the curve (AUC) of sLAG3 level was significant (P < 0.05). The sLAG3 level in subjects with body mass index (BMI) ≥ 24 kg/m2 was lower compared to those with BMI < 24 kg/m2 (P < 0.05). The sLAG3 level was also negatively associated with BMI and diabetes mellitus (P < 0.05), though not associated with the Gensini scores or EF (P > 0.05). Lastly, the LAG3 gene expression in peripheral whole blood of patients with CAD were down-regulated compared to healthy controls (P < 0.05). Conclusion: The sLAG3 level was negatively associated with the occurrence but not severity of CAD. Meanwhile, the sLAG3 was negatively associated with BMI and diabetes mellitus, suggesting the reduced sLAG3 might be a novel risk factor for developing CAD.

PCSK9 inhibition protects against myocardial ischemia-reperfusion injury via suppressing autophagy.

OBJECTIVES: Autophagy is critical for myocardial ischemia-reperfusion (I/R) injury. However, there is still considerable debate over its protective and deleterious effects. The purpose of this study was to determine the involvement of the proprotein convertase subtilisin/Kexin type 9 (PCSK9) and its inhibitor in myocardial ischemia-reperfusion injury autophagy (MRI). METHODS: Nine groups of eighty rats were used: sham, I/R2 h, I/R4 h, I/R6 h, I/R8 h, I/R1 d, and I/R2 d. A 30-min coronary artery blockage was used to produce myocardial IR. The time required for reperfusion rose linearly with the time gradient, from 2 h to 2 days. Following the determination of the best reperfusion period, three groups were formed: sham, I/R, and I/R + P (PCSK9 inhibitor (evolocumab) 10 mg/kg diluted in 2 ml sterile injection water was administered subcutaneously 1 week and half an hour before to surgery. Each group's infarction area was determined by electrocardiography (ECG), cardiac function, and 2,3,5-triphenyltetrazolium chloride (TTC) /Evan Blue (EB) staining. To detect morphological alterations in myocardial cells in each group, hematoxylin and eosin (HE) staining was used. Meanwhile, western blotting, immunohistochemistry, and Masson trichrome staining were utilized to quantify myocardial fibrosis and PCSK9 and autophagy protein expression. RESULTS: The results indicated that PCSK9 expression levels increased significantly in MRI, as indicated by increased levels of the autophagy regulatory protein light chain 3 (LC3) and Beclin-1, which activated autophagy in cardiomyocytes, exacerbated myocardial injury, and increased the size of myocardial infarcts. Meanwhile, PCSK9 regulates mitophagy via the Bcl-2/adenovirus E1B 19-kDa interacting protein (BNIP3) pathway, which controls myocardial infarction MRI throughout. Additionally, the PCSK9 inhibitor significantly decreased autophagy, enhanced cardiac function, and reduced the extent of reperfusion injury, consequently reducing myocardial infarct size expansion. CONCLUSION: PCSK9 is upregulated in the myocardial ischemia-reperfusion injury hearts and regulates mitophagy via the BNIP3 pathway, which in turn contributes to reperfusion injury after myocardial infarction. PCSK9 inhibition protects against myocardial ischemia-reperfusion injury via suppressing autophagy.

Confinement of all-inorganic perovskite quantum dots assembled in metal-organic frameworks for ultrafast scintillator application.

Nucleation and growth of quantum dots (QDs) are thermodynamic processes driven by the total Gibbs free energy change (ΔG). We discuss the nucleation and growth theory of perovskite quantum dots (PeQDs) inside a metal-organic framework (MOF) as a strong constraint framework, which can effectively confine the size of QDs below 3 nm and achieve a scintillator with an ultra-fast transient lifetime of fluorescence. Therefore, based on the requirements for the optical properties of ultra-fast scintillation materials, two kinds of suitable MOFs (UiO-67-bpy and MIL-101(Cr)) were selected for synthesis. The method of 'ship-in-bottle' was adopted to embed perovskite quantum dots CsPbBrCl2 into MOF cages to form PeQDs@MOF composite materials, which is different from the one-pot method. In order to further improve the stability of PeQDs@MOF, polystyrene was used to cure the composite scintillator, which can resist exposure to UV light and withstand the ISO level 4 test, with the fastest transient lifetime of 2.13 ns and a fluorescence emission wavelength of 445 nm.

Downregulation of TIGIT Expression in FOXP3+Regulatory T Cells in Acute Coronary Syndrome.

OBJECTIVE: Little is currently known on the role of T-cell immunoglobulin and ITIM domain (TIGIT) expression in Foxp3+ regulatory T cells (TIGIT+Tregs) in acute coronary syndrome (ACS) patients. The aim of this study was to investigate the role and alterations of TIGIT+Tregs in ACS patients. METHODS: We enrolled 117 subjects, including 61 ACS patients, 26 chronic coronary syndrome (CCS) patients, and 30 control subjects without coronary artery disease. The quantification of TIGIT+Tregs was determined by flow cytometry; serum interleukin-6 (IL-6) and transforming growth factor-ß (TGF-ß) were also measured. RESULTS: TIGIT+Tregs expression was significantly lower in ACS patients compared with CCS and control patients (P<0.05). The expression of TIGIT+Tregs was comparable in patients with and without traditional risk factors (P>0.05). Logistic regression analysis revealed that TIGIT+Tregs levels are independent predictors of ACS (P<0.01). Receiver-operating characteristic (ROC) curve analysis showed the expression levels of TIGIT+Tregs had a discriminative power for ACS (P<0.01). IL-6 levels were increased (P<0.01), while TGF-ß was decreased in ACS patients compared with CCS and control patients (P<0.01). Meanwhile, an inverse correlation between IL-6 and TIGIT+Tregs was observed (P<0.01), while a positive correlation between TGF-ß and TIGIT+Tregs was found (P<0.05). CONCLUSION: TIGIT+Tregs levels are significantly reduced in ACS, accompanied by upregulated IL-6 and downregulated TGF-ß expression. The downregulated TIGIT+Tregs are independent predictors of ACS. These findings suggest that TIGIT+Tregs may have an anti-inflammatory and protective effect on ACS, and its decreased expression may be associated with atherosclerotic plaque destabilization.