ABSTRACT
Background:
Systemic
inflammation may cause endothelial activation, mediate local
inflammation, and accelerate progression of
atherosclerosis. We examined whether the levels of circulating inflammatory
cytokines reflect local vascular
inflammation and
oxidative stress in two types of
human arteries.
Methods:
Human internal mammary artery (IMA) was obtained in 69
patients undergoing
coronary artery bypass graft (CABG)
surgery and left anterior descending (LAD)
artery was obtained in 17
patients undergoing
heart transplantation (HTx).
Plasma levels of
tumor necrosis factor α (TNF-α),
interleukin-6 (
IL-6) and
interleukin-1ß (
IL-1ß) were measured using
ELISA, high-
sensitivity C-reactive protein (
hs-CRP) was measured using Luminex, and
mRNA expression of proinflammatory
cytokines in the vascular
tissues was assessed. Furthermore, formation of
superoxide anion was measured in segments of IMA using 5â
uM lucigenin-dependent
chemiluminescence. Vascular reactivity was measured using
tissue organ
bath system.
Results:
TNF-α,
IL-6 and
IL-1ß mRNAs were expressed in all studied IMA and LAD segments.
Plasma levels of inflammatory
cytokines did not correlate with vascular
cytokine mRNA expression neither in IMA nor in LAD.
Plasma TNF-α and
IL-6 correlated with
hs-CRP level in CABG group.
Hs-CRP also correlated with TNF-α in HTx group. Neither vascular TNF-α,
IL-6 and
IL-1ß
mRNA expression, nor systemic levels of either TNF-α,
IL-6 and
IL-1ß were correlated with
superoxide generation in IMAs. Interestingly, circulating
IL-1ß negatively correlated with maximal
relaxation of the
internal mammary artery (r = -0.37, p = 0.004). At the same
time the
mRNA expression of studied inflammatory
cytokines were positively associated with each other in both IMA and LAD. The positive correlations were observed between circulating levels of
IL-6 and TNF-α in CABG cohort and
IL-6 and
IL-1ß in HTx cohort.
Conclusions:
This study shows that peripheral inflammatory
cytokine measurements may not reflect local vascular
inflammation or
oxidative stress in
patients with advanced
cardiovascular disease (CVD). Circulating pro-inflammatory
cytokines generally correlated positively with each other, similarly their
mRNA correlated in the arterial wall, however, these levels were not correlated between the studied compartments.