The Role of Natural Killer (NK) Cells in Acute Coronary Syndrome: A Comprehensive Review

Abstract

With poor outcomes and an immense financial burden, acute coronary syndrome (ACS) and its ischemic repercussions still present a major global health problem. Unfavorable outcomes seem to be mainly due to adverse cardiac remodeling. Since the inflammatory response takes an important role in remodeling secondary to myocardial infarction (MI), and as inflammation in this manner has not been completely elucidated, we attempted to give rise to a further understanding of ACS pathophysiology. Hence, in this review, we integrated current knowledge of complex communication networks between natural killer (NK) cells and immune and resident heart cells in the context of ACS. Based on available data, the role of NK cells seems to be important in the infarcted myocardium, where it affects heart remodeling. On the other hand, in atherosclerotic plaque, NK cells seem to be mere passers-by, except in the case of chronic infections by atherogenic pathogens. In that case, NK cells seem to support proinflammatory milieu. NK cell research is challenging due to ethical reasons, convergent evolution, and phenotypic diversity among individuals. Therefore, we argue that further research of NK cells in ACS is valuable, given their therapeutic potential in improving postischemic heart remodeling.

Keywords: acute myocardial infarction; cardiac remodeling; coronary artery disease; heart failure; inflammation; natural killer cells.

Figure 1

Schematic representation of NK cells’ role in acute coronary syndrome with indicated potential therapeutic targets. Blue lines and “+” represent therapeutic options that stimulate NK cell function, whereas red lines and “−“ represent therapeutic options that inhibit NK cell function. Abbreviations: RAAS: renin–angiotensin–aldosterone system; RAI-1: retinoic-acid-induced 1; DNAM-1: DNAX accessory molecule-1; NKG2D: natural killer group 2D, CD: cluster of differentiation; IFN-γ: interferon-γ.