ST2L expression on monocyte subsets is associated with acute coronary syndrome severity and plaque vulnerability

Pro-inflammatory monocyte infiltration and conversion to macrophages are established contributors to acute coronary syndrome (ACS) and plaque instability as visualized by optical coherence tomography (OCT). Increased serum levels of soluble ST2 isoform (sST2) predict poor outcomes in patients with ACS and heart failure. However, whether the transmembrane ST2 isoform (ST2L) can be used to assess the severity of ACS and plaque vulnerability early in the disease course remains elusive.

Flow cytometry and ELISA were performed to evaluate the levels of ST2L on different monocyte subsets in ACS patients and serum concentration of sST2. Bone marrow-derived macrophages were isolated and then polarized to M1 or M2 phenotype, and ST2L expression levels were detected by quantitative RT-PCR and immunoblotting.

We observed that the proportion and absolute number of ST2L expressing cells among monocyte subsets 1 (Mon1) and Mon2 were significantly lower, accompanied with increased serum sST2, in ACS patients as compared to controls. However, only the proportion of ST2L⁺/Mon2 was closely associated with the severity of atherosclerotic plaques. With regard to plaque instability, patients with thin cap fibrous atheroma (TCFA) identified by optical coherence tomography (OCT) had a lower absolute number (non-TCFA 1.26 × 10⁴ ±0.63 × 10⁴/ml vs. TCFA 0.92 × 10⁴ ±0.37 × 10⁴/ml, p = 0.034) and lower percentage (non-TCFA 17.65% ±3.10% vs. TCFA 13.17% ±2.29%, p < 0.001) of ST2L⁺/Mon2 than those without TCFA. In multivariate analysis, the proportion of ST2L⁺/Mon2 was independently associated with TCFA. In bone marrow-derived macrophages, sST2 and ST2L were highly expressed in M2 macrophage.

Compared to circulating sST2, the proportion of ST2L-expressing Mon2 subsets was more strongly associated with the severity of ACS and plaque vulnerability.