Abstract 15301: Peripheral CD56 ^bright Natural Killer Cells Associate With Increased Atheroburden and Unstable Plaque Features in Humans

Abstract

Background: Atherosclerotic plaques in mice and humans contain natural killer (NK) cells. Data on the role of NK cells in atherosclerosis using different transgenic mice models is inconsistent. Some studies showed that NK cells augment atherosclerosis through their cytotoxic potential, while others reported no effect. Evidence in humans indicates that NK cells are atherogenic. Frequency of NK cells and expression of the activating NK cell receptors are associated with severe disease and symptomatic carotid atherosclerotic plaques in humans. Hypothesis: We tested if coronary artery disease (CAD) subjects with necrotic plaques have a higher frequency of the circulating NK cells. Methods: We performed mass cytometry on peripheral blood mononuclear cells from matched CAD subjects with low and high (n=9 each) necrotic plaque content as determined by intravascular ultrasound-virtual histology. Results: CAD subjects with high necrotic plaques have significantly higher atheroburden, stenosis, calcium, fatty plaque content, and lower plaque fibrosis. Interestingly, CAD subjects with high necrotic plaques exhibited a significantly higher frequency of the CD56 bright NK cells as compared to those with low necrotic plaques (4.618 ± 0.625 vs 2.481 ± 0.37; p=0.011). Moreover, frequency of CD25 + NK cells also trended to be higher in subjects with high necrotic plaques. The frequency of the cytotoxic CD56 dim NK cells did not differ between the two groups. Correlation analyses demonstrated a significant positive association of CD56 bright NK cells with atheroburden (r=0.43; p=0.04), stenosis (r=0.58; p=0.005), plaque necrotic (r=0.71; p=0.002), calcium contents (r=0.73; p=0.0001), and a negative association with the plaque fibrous content (r=0.71; p= 0.0003). CD25 + NK cells also showed similar trending associations with burden, stenosis and plaque features. Conclusions: Our data provides yet another evidence of the atherogenic role of NK cells in humans and indicates that the CD56 bright NK cells may contribute to the development of a vulnerable plaque. CD56 bright NK cells produce proinflammatory cytokines including IFN-γ and TNF-α and cytotoxic enzymes that may contribute to increased inflammation, cell activation, and apoptosis within the plaque.