Unstable coronary artery plaque features in humans are associated with higher frequency of circulating CD56bright Natural Killer Cells.

Abstract

Unstable human artery plaques can suddenly rupture, leading to MI or stroke. Identification of blood markers associated with unstable plaque features is clearly needed. Humans with symptomatic carotid atherosclerotic plaques have increased plaque infiltration of CD56bright Natural Killer (NK) cells, yet whether subjects with unstable coronary artery plaque features have increased frequencies of circulating CD56bright NK cells is unknown. Coronary artery intravascular ultrasound (IVUS) was performed on subjects presenting for medically-indicated coronary angiography. 18 subjects stratified into high and low percent (%) necrotic core matched for age, BMI, and lipids underwent Mass Cytometry (CyTOF) analysis on their peripheral blood mononuclear cells (PBMCs). Clustering of major PBMC populations was performed on live singlets and CD56 bright and dim NK subsets were quantitated. Subjects with high necrotic core had significantly greater frequency of circulating CD56bright NK cells compared to subjects with low necrotic core (p=0.02). Additionally, frequency of CD56bright NK cells positively associated with IVUS-VH metrics of total atheroma volume (TAV) (p=0.0013), percent (%) atheroma burden (p=0.0048), % maximum stenosis (p=0.0021), % necrotic (p=0.0013), % calcium (p=0.0016)) and negatively associated with % fibrous (p<0.0001). These findings suggest that frequency of CD56bright NK cells may be a safe, non-invasive marker of plaque volume and instability.