NFAT activating protein with ITAM motif 1 (NFAM1) is upregulated on circulating monocytes in coronary artery disease and potentially correlated with monocyte chemotaxis

Background and aims: Circulating monocytes have been proven to be critical mediators in the propagation and progression of atherosclerosis and myocardial infarction. The present study was designed to characterise a new transmembrane protein-NFAT activating protein with ITAM motif 1 (NFAM1)-on monocytes and uncover the potential effects and underlying mechanisms in coronary artery disease.

Methods: Monocytes from a population of four controls, five stable coronary artery disease patients and five acute coronary syndrome patients were isolated for RNA sequencing. A potential monocyte biomarker molecule was discovered and then validated with a group of 79 controls, 70 stable coronary artery disease patients and 183 acute coronary syndrome patients. A stable cell line was generated as an in vitro model to determine chemotaxis migration and chemokine receptor expression.

Results: NFAM1 was identified through RNA sequencing analysis. The validation results confirmed that NFAM1 expression on monocytes was significantly increased by coronary artery disease status. A higher expression level of NFAM1 on classical and intermediate monocytes was observed compared with that on nonclassical monocytes. As shown in the in vitro cell model, knockdown of NFAM1 significantly attenuated chemotactic migration of monocytes by downregulating chemokine receptor expression and the p38 MAPK signalling pathway. Multivariable regression analysis of a group of 16 individuals suggested that NFAM1 was positively correlated with CCR2 expression.

Conclusions: The present study reported for the first time that distinctive alterations of NFAM1 expression on monocytes may correlate with atherosclerosis pathobiology and serve as a potential monocyte biomarker and therapeutic target for coronary artery disease.