Endocrine Abstracts (2004) 7 P50

Circulating pro-inflammatory cytokines and epicardial expression of resistin and TNF-alpha are increased in patients with cardiovascular disease

AR Baker1, DW Quinn2, NF da Silva1, CL McTernan1, AL Harte1, RS Bonser2, S Kumar1 & PG McTernan1


1Unit for Diabetes and Metabolism, Warwick Medical School,Gibbet Hill Campus, University of Warwick, Coventry, UK; 2Department of Cardiothoracic surgery, University of Birmingham, UK.


Chronic sub-clinical inflammation is associated with increased risk of diabetes and cardiovascular disease and is particularly observed in patients that have undergone CABG. Resistin, a novel adipocyte derived protein, has been linked with central adiposity, insulin resistance and sub-clinical inflammation and may mediate both systemic and local paracrine pro-inflammatory responses in vivo. As such we investigated serum resistin from CABG patients and examined whether epicardial adipose tissue produces pro-inflammatory markers including resistin, that may exert paracrine effects on myocardial metabolism. In this study serum was taken from CABG patients (Age: 67plus/minus(SD)10.2; BMI: 27.6plus/minus(SD)3.4; n=20) and BMI matched controls (Age:58plus/minus12.4; BMI: 29.3plus/minus5.8; n=20) to measure a panel of pro-inflammatory cytokines (including: resistin, IL-6 and TNF-alpha). mRNA expression of resistin, IL-6, TNF-alpha and other pro-inflammatory agents were determined by real-time PCR in epicardial fat from CABG patients against other fat depots from control subjects. Pro-inflammatory cytokines were significantly elevated in serum from CABG patients compared to healthy controls (Resistin: 12.6plus/minus3.3 nanograms per millilitre vs CABG: 19.8plus/minus4.56 nanograms per millilitre**; **p<0.001; TNF-alpha: Control subjects: 38.6plus/minus4.5 picograms per millilitre vs CABG: 64plus/minus7.7 picograms per millilitre***; ***p<0.0001; IL-6: Control subjects: 56plus/minus7.9 picograms per millilitre Vs CABG 104plus/minus46 picograms per millilitre**). Further analysis of resistin mRNA expression determined a 2.7 fold higher level of resistin in epicardial than in thigh fat (deltaCt: 23.3plus/minus0.43; p=0.0155). While epicardial resistin expression was comparable to expression levels in abdominal fat depots (Abd Sc: deltaCt 21.02plus/minus0.05; Abd Om: deltaCt 21.27plus/minus0.78). In addition, IL-6, TNF-alpha, AGT, PAI-1/tPA mRNA from epicardial fat showed a similar expression pattern when compared with other abdominal fat depots. These findings imply resistin as a contributory factor in activation of the inflammatory response from epicardial fat. Furthermore these factors may mediate direct paracrine effects on myocardial metabolism,through their known biological effects.

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