Relation of circulating lncRNA GAS5 and miR‐21 with biochemical indexes, stenosis severity, and inflammatory cytokines in coronary heart disease patients

The study is aimed at elucidating the relationship between the blood b-endorphin level in patients with coronary heart disease (CHD) with metabolic syndrome (MS) and cardiovascular risk factors and evaluating the possibility to correct them by dalargin therapy. The study included 123 patients (61 men and 62 women) at the mean age 57.6±5,2 years randomized into 2 groups. The patients of group 1 (n=63) were given the standard treatment, those of group 2 (n=60) additionally received 2 mg/day of dalargin for 10 days (3 courses during 3 months). The group of comparison (n=84) contained 84 CHD patients without MS. Biochemical and immunological characteristics were measured by immunoenzyme and immunochemiluminescent assays before and 3 months after treatment. The study revealed inverse correlation between b-endorphin levels and those of leptin, insulin, cortisol, TNF-a, IL-6, oxidized LDLP, triglycerides (TG), and HDLP cholesterol. Standard therapy resulted in a 6.5% reduction ofinsulin level, 9,4% , 6,1%, and 17,4% reduction of TNF-a , IL-6, TG levels respectively; it increased the HDLP cholesterol level by 10,3% (p<0,05 for all values) but did not change other parameters of interest. Dalargin therapy caused a 32,6% and 17,4%, rise in the b-endorphin and HDLP cholesterol levels but decreased leptin, insulin, cortisol, TNF-a, IL-6, LDLP, and tG levels by 36,1%, 22,4%, 23,9%, 55%, 56,3%, 14% and 27,2% respectively (p<0,001). It is concluded that the decrease of the blood b-endorphin level in the patients with coronary heart disease and metabolic syndrome is associated with enhanced blood atherogenicity, hyperinsulinemia, hypercortisolemia, activation of pro-inflammatory cytokines and lipid peroxidation. Supplementation of conventional therapy with dalargin results in the increased b-endorphin level, enhanced anti-atherogenic effect, reduced activity ofpro-inflammatory cytokines and lipid peroxidation, reduction of leptin, insulin and cortisol levels.

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LncRNA UCA1, miR‐26a, and miR‐195 in coronary heart disease patients: Correlation with stenosis degree, cholesterol levels, inflammatory cytokines, and cell adhesion molecules

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.24070 ◽

2021 ◽

Author(s):

Jie Li ◽

Zhisong Chen ◽

Xiaoyan Wang ◽

Haoming Song

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Cell Adhesion ◽

Adhesion Molecules ◽

Inflammatory Cytokines ◽

Cell Adhesion Molecules ◽

Cholesterol Levels

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Inflammatory Cytokine Levels in Pulmonary Embolism Severity: A Retrospective Study

10.21203/rs.3.rs-1197499/v1 ◽

2021 ◽

Author(s):

Xiaoming Li ◽

Yukun Li ◽

Wenjing Ye ◽

Xi Chen ◽

Xuejun Guo ◽

...

Keyword(s):

Coronary Heart Disease ◽

Pulmonary Embolism ◽

Logistic Regression ◽

Regression Analysis ◽

Heart Disease ◽

Respiratory Failure ◽

Venous Thrombosis ◽

Inflammatory Cytokines ◽

Multivariate Logistic Regression Analysis ◽

Multivariate Logistic Regression

Abstract Background: Inflammatory cytokines are involved in the development of venous thromboembolism (VTE) and may influence the mortality. But the association between their levels and severity of pulmonary embolism (PE) is unclear. This study aimed to investigate the association of inflammatory cytokines and PE severity. Methods: We retrospectively analyzed patients who were admitted to Xinhua Hospital with a confirmed diagnosis of PE between Jan 2019 and Apr 2021. Inflammatory cytokines were compared among different severities of PE groups. Spearman rank-order correlation analysis and multivariate Logistic regression analysis were used to analyze the relationship between cytokine level and PE severity. In addition, we estimated the association between comorbidities and PE severity by using multivariate Logistic regression analysis. Results: A negative correlation between IL-8 level and PE severity was found (r=-0.466, P=0.018). Comorbidities of coronary heart disease [3.76 (1.99-7.10) (P=0.000)], deep venous thrombosis [2.40 (1.15-5.01) (P=0.019)], respiratory failure [2.92 (1.33-6.4) (P=0.007)] were correlated with the severity of PE. Conclusions: IL-8 level is negative correlated with PE severity. Patients with comorbidities regarding coronary heart disease, deep venous thrombosis, and respiratory failure may have higher risk to surfer a more sever PE.

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Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis

European Heart Journal ◽

10.1093/eurheartj/eht367 ◽

2013 ◽

Vol 35 (9) ◽

pp. 578-589 ◽

Cited By ~ 265

Author(s):

S. Kaptoge ◽

S. R. K. Seshasai ◽

P. Gao ◽

D. F. Freitag ◽

A. S. Butterworth ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Prospective Study ◽

Inflammatory Cytokines ◽

Meta Analysis

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The action of metformin on the production of pro-inflammatory cytokines and insulin resistance (NF-kB signal pathway)

Problems of Endocrinology ◽

10.14341/probl201258225-28 ◽

2012 ◽

Vol 58 (2) ◽

pp. 25-28

Author(s):

A V Lavrenko ◽

N L Kutsenko ◽

L A Kutsenko ◽

T V Mamontova ◽

I P Kaĭdashev

Keyword(s):

Metabolic Syndrome ◽

Coronary Heart Disease ◽

Heart Disease ◽

Inflammatory Cytokines ◽

Combined Treatment ◽

Signal Pathway ◽

Tnf Alpha ◽

Peptide Level ◽

Pro Inflammatory Cytokines

The objective of the present study was to estimate the role of the NF-kB signal pathway in the realization of the anti-inflammatory and insulin-synthesizing activities of metformin in the patients presenting with coronary heart disease (CHD) associated with metabolic syndrome (MS). It was shown that the introduction of a one-month course of metformin therapy in the combined treatment of CHD resulted in the decreased production of pro-inflammatory cytokines, such as IL-1-beta, IL-6, IL-8, and TNF-alpha. Simultaneously, the serum C-peptide level decreased. These effects of metformin were mediated through the NF-kB-signal pathway. It is concluded that the inclusion of metformin in the combined treatment of coronary heart disease in the patients with metabolic syndrome prevent activation of NF-kB under the influence of endogeneous pro-inflammatory cytokines.

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Targeting the NF-κb-Dependent HIF-1β Pathway Reprograms Macrophage Polarization Induced By Oxidized LDL

Blood ◽

10.1182/blood.v130.suppl_1.993.993 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 993-993

Author(s):

Jin Fengyan ◽

Wang Xue ◽

Wu Jiang ◽

Yun Dai

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Cell Line ◽

Inflammatory Cytokines ◽

Macrophage Polarization ◽

Human Macrophages ◽

M2 Polarization ◽

M1 Polarization ◽

Anti Inflammatory ◽

Hif Pathway

Abstract Introduction: Plasticity is one of the hallmarks of macrophages, an essential component of innate and adaptive immunity. In response to various stimuli, macrophages can differentiate or polarize to either pro-inflammatory M1 or anti-inflammatory M2 phenotype, which determines whether inflammation is initiated and promoted or terminated and resolved. Of note, the phenotype of polarized M1-M2 macrophages may be reversed in certain circumstances, providing an opportunity to treat inflammatory disorders (e.g., atherosclerosis) and inflammation-related diseases (e.g., cancer) by targeting macrophage polarization. Emerging evidence supports that transcriptional regulation play an important role in polarization and function of macrophages via reprogramming expression of pro- versus anti-inflammatory genes. However, despite well-established cross-talk between two major transcriptional factors, NF-κB and hypoxia-inducible factor (HIF), it remains unclear whether NF-κB interacts with HIFs (particularly HIF-1β, a regulatory subunit of the active HIF complex) in reprogramming macrophages. Here, we investigated the mechanism underlying macrophage activation induced by oxidized low density lipoprotein (oxLDL), a central event of uncontrolled inflammation in atherosclerosis. Materials and Methods: The murine macrophage cell line RAW264.7 and human THP-1 cell line-derived macrophages were employed. After exposed to oxLDL, cells were analyzed by qPCR, Western blot, flow cytometry (Cytometric Bead Array, CBA), and ELISA analyses to monitor expression of M1 and M2 markers and related cytokines, as well as activation of the NF-κB and HIF pathways. The shRNA approach was used to knock down expression of target genes for functional evaluation. The findings from in vitro experiments involving cell lines were then validated in primary samples obtained from healthy donors (n = 10) and patients with coronary heart disease (n = 22) and stroke (n = 11). Results: Exposure to oxLDL triggered M1 polarization of murine and human macrophages, characterized by expression of iNOS and robust production of M1 pro-inflammatory cytokines (e.g., TNF-α, MCP-1, IL-1β, IL-6) but not M2 anti-inflammatory cytokines (e.g., IL-10, TGF-β). In contrast, protein level of the M2 marker Arg1 was clearly decreased after treated with oxLDL. Notably, exposure of macrophages to oxLDL resulted in markedly increased expression of HIF-1α and -1β, in association with activation of both canonical and non-canonical NF-κB pathways. Functionally, whereas inhibition of NF-κB activation by the IKK inhibitor parthenolide almost completely prevented M1 polarization and promoted M2 polarization, knockdown of HIF-1β by shRNA also largely reversed macrophage polarization from M1 to M2 after exposed to oxLDL. These results were confirmed in human macrophages differentiated by PMA from primary peripheral blood monocytes obtained from patients with coronary heart disease or ischemic stroke, and normal donors. These events were accompanied by a clear reversal of oxLDL-induced morphological changes of macrophages. Mechanistically, inhibition of NF-κB activation dramatically diminished expression of HIF-1α and -1β induced by oxLDL. However, while shRNA knockdown of HIF-1β sharply blocked HIF-1α expression in macrophages exposed to oxLDL, it failed to impair activation of NF-κB. These findings indicate that oxLDL-induced HIF-1β expression is dependent on NF-κB activation, which in turn activates the HIF pathway via HIF-1α up-regulation probably by stabilizing HIF-1α protein. Conclusion: HIF-1β (encoded by ARNT) is identified for the first time as a novel target that reprograms M1-M2 polarization of macrophages, at least after exposure to oxLDL, a risk factor of atherosclerosis. HIF-1β is further demonstrated to act as downstream of NF-κB to induce activation of the HIF pathway. Importantly, these findings suggest that HIF-1β might serve as a therapeutic target for the treatment of inflammatory disorders such as atherosclerosis, and probably immune diseases and cancer as well. Disclosures No relevant conflicts of interest to declare.

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AK098656: a new biomarker of coronary stenosis severity in hypertensive and coronary heart disease patients

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-022-00783-3 ◽

2022 ◽

Vol 14 (1) ◽

Author(s):

Xin Wang ◽

Ya-li Wu ◽

Yuan-yuan Zhang ◽

Jing Ke ◽

Zong-wei Wang ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Roc Curve ◽

Coronary Stenosis ◽

Area Under The Curve ◽

Discrimination Ability ◽

Chd Risk ◽

Significant Difference ◽

Stenosis Severity ◽

Novel Target

Abstract Background AK098656 may be an adverse factor for coronary heart disease (CHD), especially in patients with hypertension. This study aimed to analyze the effect of AK098656 on CHD and CHD with various complications. Methods A total of 117 CHD patients and 27 healthy control subjects were enrolled in the study. Plasma AK098656 expression was determined using the quantitative real-time polymerase chain reaction. Student’s t-test was used to compare AK098656 expression levels in different groups. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to quantify the discrimination ability between CHD patients and health controls and between CHD and CHD + complications patients. The relationship between AK098656 and coronary stenosis was analyzed using Spearman’s correlation. Results AK098656 expression was remarkably higher in CHD patients than in healthy controls (P = 0.03). The ROC curve revealed an effective predictive AK098656 expression value for CHD risk, with an AUC of 0.656 (95% CI 0.501–0.809). Moreover, AK098656 expression was increased in CHD + complications patients compared to CHD patients alone (P = 0.005), especially in patients with hypertension (CHD + hHTN, P = 0.030). The ROC curve revealed a predictive AK098656 prognostic value for discriminating between CHD and CHD + hHTN patients, with an AUC of 0.666 (95% CI 0.528–0.805). There was no significant difference in AK098656 expression in CHD patients with diabetes mellitus compared to CHD patients alone. In addition, AK098656 expression in CHD patients was positively correlated with stenosis severity (R = 0.261, P = 0.006). Conclusion AK098656 expression was significantly increased in patients with CHD, especially those with hypertension, and its expression level was positively correlated with the degree of coronary stenosis. This implied that AK098656 may be a risk factor for CHD and can potentially be applied in clinical diagnosis or provide a novel target for treatment.

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