Epicardial Adipocyte-derived TNF-α Modulates Local Inflammation in Patients with Advanced Coronary Artery Disease

Background: Epicardial adipose tissue (EAT) surrounds the epicardium and can mediate harmful effects related to coronary artery disease (CAD). Objective: We explored the regional differences between adipose stores surrounding diseased and non-diseased segments of coronary arteries in patients with advanced CAD. Methods: We enrolled 32 patients with known CAD who underwent coronary artery bypass graft (CABG) surgery. Inflammatory mediators were measured in EAT biopsies collected from a region of the left anterior descending artery (LAD) with severe stenosis (diseased segment) and without stenosis (non-diseased segment). Results : Mean age was 64.3±11.1 years, and mean EAT thickness was 7.4±1.9 mm. Dyslipidemia was the most prevalent comorbidity (81% of the patients). Out of a total of 11 cytokines, resistin (p=0.039), matrix metallopeptidase 9 (MMP-9) (p=0.020), C-C motif chemokine ligand 5 (CCL-5) (p=0.021), and follistatin (p=0.038) were significantly increased in the diseased compared with the non-diseased EAT segments. Indexed tumor necrosis factor-alpha (TNF-α), defined as the diseased to non-diseased cytokine levels ratio, was significantly correlated with increased EAT thickness both in the whole cohort (p=0.043) and in a subpopulation of patients with dyslipidemia (p=0.009). Treatment with lipid-lowering agents significantly decreased indexed TNF-α levels (p=0.015). No significant alterations were observed in the circulating levels of these cytokines with respect to CAD-associated comorbidities. Conclusion: Perivascular EAT is a source of cytokine secretion in distinct areas surrounding the coronary arteries in patients with advanced CAD. Adipocyte-derived TNF-α is a prominent mediator of local inflammation.

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Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

Clinical Science ◽

10.1042/cs20190999 ◽

2019 ◽

Vol 133 (22) ◽

pp. 2283-2299

Author(s):

Apabrita Ayan Das ◽

Devasmita Chakravarty ◽

Debmalya Bhunia ◽

Surajit Ghosh ◽

Prakash C. Mandal ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Chronic Inflammation ◽

Ex Vivo ◽

Human Subjects ◽

Critical Role ◽

Atherosclerotic Cardiovascular Disease ◽

Tnf Α ◽

Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

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Reproducibility of quantitative plaque measurement in advanced coronary artery disease

Journal of Cardiovascular Computed Tomography ◽

10.1016/j.jcct.2020.12.008 ◽

2020 ◽

Author(s):

Mohammed N. Meah ◽

Trisha Singh ◽

Michelle C. Williams ◽

Marc R. Dweck ◽

David E. Newby ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Artery Disease ◽

Advanced Coronary Artery Disease

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Improved long-term survival after aortocoronary bypass for advanced coronary artery disease

The American Journal of Surgery ◽

10.1016/0002-9610(75)90181-6 ◽

1975 ◽

Vol 129 (4) ◽

pp. 380-385 ◽

Cited By ~ 51

Author(s):

Lawrence H. Cohn ◽

Caryl M. Boyden ◽

John J. Collins

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Aortocoronary Bypass ◽

Term Survival ◽

Long Term Survival ◽

Artery Disease ◽

Advanced Coronary Artery Disease

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THE ASSOCIATION BETWEEN LOCAL INFLAMMATION AND THE PRESENCE OF UNRECOGNIZED MYOCARDIAL INFARCTION IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(21)02802-3 ◽

2021 ◽

Vol 77 (18) ◽

pp. 1444

Author(s):

Yumi Yasui ◽

Yoshihisa Kanaji ◽

Tomoyo Sugiyama ◽

Masahiro Hoshino ◽

Masao Yamaguchi ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Stable Coronary Artery Disease ◽

Local Inflammation ◽

Artery Disease

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Association of TNF-α (-308G/A) Gene Polymorphism with Circulating TNF-α Levels and Excessive Daytime Sleepiness in Adults with Coronary Artery Disease and Concomitant Obstructive Sleep Apnea

Journal of Clinical Medicine ◽

10.3390/jcm10153413 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3413

Author(s):

Afrouz Behboudi ◽

Tilia Thelander ◽

Duygu Yazici ◽

Yeliz Celik ◽

Tülay Yucel-Lindberg ◽

...

Keyword(s):

Coronary Artery Disease ◽

Obstructive Sleep Apnea ◽

Coronary Artery ◽

Sleep Apnea ◽

Gene Polymorphism ◽

Excessive Daytime Sleepiness ◽

Daytime Sleepiness ◽

Obstructive Sleep ◽

Tnf Α ◽

Artery Disease

Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), in which inflammatory activity has a crucial role. The manifestation of OSA varies significantly between individuals in clinical cohorts; not all adults with OSA demonstrate the same set of symptoms; i.e., excessive daytime sleepiness (EDS) and/or increased levels of inflammatory biomarkers. The further exploration of the molecular basis of these differences is therefore essential for a better understanding of the OSA phenotypes in cardiac patients. In this current secondary analysis of the Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA (RICCADSA) trial (Trial Registry: ClinicalTrials.gov; No: NCT 00519597), we aimed to address the association of tumor necrosis factor alpha (TNF-α)-308G/A gene polymorphism with circulating TNF-α levels and EDS among 326 participants. CAD patients with OSA (apnea–hypopnea-index (AHI) ≥ 15 events/h; n = 256) were categorized as having EDS (n = 100) or no-EDS (n = 156) based on the Epworth Sleepiness Scale score with a cut-off of 10. CAD patients with no-OSA (AHI < 5 events/h; n = 70) were included as a control group. The results demonstrated no significant differences regarding the distribution of the TNF-α alleles and genotypes between CAD patients with vs. without OSA. In a multivariate analysis, the oxygen desaturation index and TNF-α genotypes from GG to GA and GA to AA as well as the TNF-α-308A allele carriage were significantly associated with the circulating TNF-α levels. Moreover, the TNF-α-308A allele was associated with a decreased risk for EDS (odds ratio 0.64, 95% confidence interval 0.41–0.99; p = 0.043) independent of age, sex, obesity, OSA severity and the circulating TNF-α levels. We conclude that the TNF-α-308A allele appears to modulate circulatory TNF-α levels and mitigate EDS in adults with CAD and concomitant OSA.

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CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-α levels

Thrombosis and Haemostasis ◽

10.1160/th04-02-0095 ◽

2004 ◽

Vol 92 (08) ◽

pp. 419-424 ◽

Cited By ~ 164

Author(s):

Stefan Blankenberg ◽

Christine Espinola-Klein ◽

Joern Dopheide ◽

Christoph Bickel ◽

Karl Lackner ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Animal Studies ◽

Inflammatory Diseases ◽

Serum Concentrations ◽

Tnf Α ◽

Hs Crp ◽

Artery Disease ◽

Fourth Quartile

SummaryMonocytes play a central role in the inflammatory disease atherosclerosis. CD14+CD16+ monocytes are considered proinflammatory monocytes, as they have an increased capacity to produce proinflammatory cytokines, such as TNF-α, and are elevated in various inflammatory diseases. We hypothesized that patients with coronary artery disease (CAD) have increased levels of CD14+CD16+ monocytes, and that CD14+CD16+ monocytes are associated with inflammation markers. We investigated CD14+CD16+ monocytes in 247 patients with CAD and 61 control subjects using flow cytometry. In addition serum concentrations of TNF-α, IL-6, and Hs-CRP were assessed. Patients with CAD had higher levels of CD14+CD16+ monocytes than controls (13.6% versus 11.4%; p<0.001). Logistic regression analysis including quartiles of CD14+CD16+ monocytes showed that CD14+CD16+ monocytes were associated with prevalence of CAD (OR 4.9, 95% CI 2.5–19.1, for subjects in the fourth quartile in comparison to subjects in the first quartile). The association between CD14+CD16+ monocytes and CAD remained independently significant after adjustment for most potential confounders (OR 5.0, 95% CI 1.2-20.0). Serum concentrations of TNF-α were elevated in subjects within the highest quartiles of CD14+CD16+ monocytes (p=0.018). Our study showed that increased numbers of CD14+CD16+ monocytes are associated with coronary atherosclerosis and TNF-α. In accordance, recent animal studies suggest a possibly important role of these monocytes in the development of atherosclerosis.

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IL-32 Serum Levels in Coronary Artery Disease Patient and its Relationship with IL-6 and TNF-α Serum Levels

10.21203/rs.3.rs-179059/v1 ◽

2021 ◽

Author(s):

Mina Mohammad-Rezaei ◽

Reza Ahmadi ◽

Ali Rafiei ◽

Arsalan Khaledifar ◽

Shohila Fatahi ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Serum Levels ◽

Arterial Stenosis ◽

Enzyme Linked Immunosorbent Assay ◽

Control Subjects ◽

Tnf Α ◽

Significant Difference ◽

Major Vessel ◽

Artery Disease

Abstract Coronary Artery Disease (CAD) is a chronic inflammatory disease caused by atherosclerosis and arteries become clogged due to plaque formation, fat accumulation, and various sorts of immune cells. IL-32 is a new proinflammatory cytokine, which enhances inflammation through inducing different inflammatory cytokines. The purpose of current research was to assess IL-32 serum levels in coronary artery disease subjects and its relationship with serum levels of IL-6 and TNF-α. Forty-two subjects diagnosed with CAD and thirty-nine control subjects were enrolled in the research. Serum levels of IL-6, TNF-α, and IL-32 were measured using the enzyme-linked immunosorbent assay (ELISA). IL-32, TNF-α, and IL-6 serum levels were significantly higher by 2.7, 3.48, and 3.2-fold in the CAD subjects than in control subjects, respectively. Moreover, no significant difference was found in TNF-α, IL-6 and IL-32 serum levels with the clogged arteries number in the CAD group. TNF-α and IL-32 serum levels in the CAD subjects with cardiac arterial stenosis in one major vessel were significantly increased than CAD subjects with cardiac arterial stenosis in more than one major vessels. ROC curve analysis revealed that serum levels of IL-32, TNF-α, and IL-6 showed good abilities in predicting CAD. Also, Multiple logistic regression analyses suggested that TNF-α, IL-6, and IL-32, serum levels of LDL and ox-LDL were independently related to the presence of CAD, while HDL serum levels were not. TNF-α, IL-32, and IL-6 showed an increase in CAD group and serum levels of these cytokines showed good abilities in predicting CAD. Our data suggested the involvement of TNF-α and IL-32 in the early stage of CAD.

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