Increased expression of inactive rhomboid protein 2 in circulating monocytes after acute myocardial infarction

Abstract

Abstract Purpose Tumor necrosis factor-alpha (TNF-α) blood levels increase following acute myocardial infarction (AMI); TNF-α is involved in impaired recovery of myocardial function following AMI. The interaction of inactive rhomboid protein 2 (iRhom2) with TNF-α converting enzyme (TACE) is required for shedding of TNF-α from the cell surface of immune cells. In this pilot study, we hypothesized that iRhom2 expression increases in circulating monocytes following AMI. Methods Circulating monocytes were MACS-sorted from peripheral blood of 50 AMI patients at admission (day 1) and 3 days after admission. mRNA was isolated from sorted monocytes and expression levels of iRhom2, TACE and TNF-α were evaluated by real-time RT-PCR. Serum TNF-α levels were determined. Circulating monocyte subsets were quantified by flow cytometry. Left ventricular (LV) function was measured by echocardiography. Results We observed a significant increase of iRhom2 mRNA expression in monocytes (p = 0.012), of intermediate monocytes levels (p < 0.001), and of serum TNF-α levels (p < 0.001) at day 3 following AMI compared to day 1. In contrast, TNF-α and TACE mRNA expression in monocytes remained unchanged. At day 3, iRhom2 mRNA expression in monocytes positively correlated with levels of intermediate monocytes (r = 0.37, p = 0.009) and serum TNF-α levels (r = 0.33, p = 0.019). iRhom2 mRNA expression in monocytes at day 3 negatively correlated with LV systolic function (r=-0.34, p = 0.025). Conclusions This study suggests that iRhom2 contributes to the regulation of inflammation and is thereby associated with LV dysfunction following AMI. Thus, iRhom2 modulation should be further evaluated as a potential therapeutic strategy to attenuate adverse cardiac remodeling in AMI patients.