Plasma concentrations of TNF‐α and its soluble receptors sTNFR1 and sTNFR2 in patients with coronary artery disease

Abstract

Tumour necrosis factor alpha (TNF-alpha) is implicated in post-ischemic myocardial dysfunction. Two distinct TNF-alpha receptors are shed from cell membranes and circulate in plasma as soluble sTNFR1 and sTNFR2 proteins. The aim of the study was to establish factors associated with plasma concentrations of TNF-alpha and its receptors in patients with coronary artery disease (CAD). Since adenosine inhibits the expression of TNF-alpha, two functional polymorphisms in genes encoding enzymes participating in adenosine metabolism, i.e. AMP deaminase-1 (AMPD1, C34T) and adenosine deaminase (ADA, G22A), were analyzed. Plasma concentrations of TNF-alpha, sTNFR1, and sTNFR2 were measured using ELISA in 167 patients with CAD. Common factors significantly associated with higher TNF-alpha, sTNFR1, and sTNFR2 were lower glomerular filtration rate (GFR), older age, higher BNP, lower blood haemoglobin, and the presence of asthma or chronic obstructive pulmonary disease (COPD). Higher TNF-alpha and sTNFR1 concentrations were also associated with the presence of heart failure (HF), lower ejection and shortening fraction, the presence of diabetes or metabolic syndrome, lower serum HDL cholesterol, and higher uric acid. In multivariate analysis the common independent predictors of higher TNF-alpha, sTNFR1, and sTNFR2 were lower GFR, lower HDL cholesterol, higher BNP, and the presence of asthma or COPD. There were no associations between AMPD1 C34T or ADA G22A genotypes and TNF-alpha or its receptors. In conclusion, the concentrations of TNF-alpha, sTNFR1, and sTNFR2 reflect the impairment of cardiac and renal function in patients with CAD. Metabolic syndrome and diabetes are associated with higher plasma concentrations of TNF-alpha and its receptors.

Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes – Findings from two community based cohorts of elderly

“…Soluble TNFR1 was shown to be cross-sectionally associated with cardiometabolic risk factors in a study of patients with coronary artery disease: elevated uric acid levels, lower HDL cholesterol, metabolic syndrome, diabetes and heart failure [21]. In accordance with our findings where sTNFR1 was associated with cardiovascular mortality after adjustments for CRP and IL-6, sTNFR1 but not IL-6 and CRP was associated with left ventricular mass in a study of over 600 patients with stroke [22].…”

“…The association between sTNFR1 and cardiovascular mortality could be explained by its direct atherosclerotic effects by being a marker of a higher systemic inflammatory state [21,25]. Inflammation does not only initiate the formation of the atherosclerotic lesion, but can also be involved in plaque rupture; the final trigger of most thrombotic and atherosclerotic events [31].…”

Association of serum omentin-1 levels with coronary artery disease

“…In addition, Yamawaki et al demonstrated a vasodilating effect of omentin on isolated blood vessels, suggesting omentin involvement in endothelial function [14] . There have been several reports showing that other adipokines, such as adiponectin [15][16][17] , resistin [17][18][19][20] , leptin [19] , visfatin [21][22][23] , TNF-α [24] , and IL-6 [25] , are related to inflammation and coronary artery disease (CAD). We hypothesized that omentin-1 might be implicated in CAD due to a possible association with inflammation and endothelial function.…”

Potential Role of Selected Biomarkers for Predicting the Presence and Extent of Coronary Artery Disease

“…The level of sTNFR2 in the circulation could therefore be interpreted as the degree of activation of TNF-α signalling in the tissues, making sTNFR2 an interesting parameter for TNF-α activation in the tissues. High levels of sTNFR2 in serum have been documented in multiple inflammatory pathologies 29,30 . Metabolic syndrome and diabetes are also associated with higher plasma concentrations of TNFalpha and its receptors 31 .…”