Introduction: Besides the well-studied plaque rupture, plaque erosion is a main culprit pathophysiology in acute coronary syndrome (ACS), responsible for more than one third of ACS cases. Plaque erosion is defined as thrombus formation on an intact fibrous cap in the absence of plaque rupture and can be accurately identified by intravascular high-resolution imaging using optical coherence tomography (OCT). Although post-mortem studies show profound differences in plaque composition, the pathomechanism of this important entity is largely unknown. We recently observed significant enrichment of cytotoxic- and helper T-cells selectively at the culprit lesion site of plaque erosion, but details of the differential inflammatory response remain unclear.

Methods: We used a novel combination of intracoronary OCT-imaging, catheter-based sample acquisition directly at ACS causing culprit plaque with subsequent flow-cytometry and multiparameter plasma proteomics in a matched cohort of 10 erosion-, 10 rupture-ACS patients and 10 patients with stable coronary artery disease (CAD).

Results: In a delicate balance, the principal CD4⁺ T-cell subsets mediate distinct pro-inflammatory, destabilizing (mainly T-helper 1- and 17.1 (T_H1, T_H17.1)) or anti-inflammatory, protective (mainly regulatory T-cells (T_reg)) effects on atherosclerosis. Pointing to a favorable immune profile in plaque erosion, we show marked local T_reg-accumulation (p<0.0001) and elevated T_reg/T_H1 and T_reg/T_H17 ratios (p<0.01) in erosion, as compared to a proinflammatory lesional T_H1 (p<0.01)-and T_H17.1 (p=0.001) accumulation in rupture-ACS. Plasma proteomics of 384 proteins reveal an overall enhanced inflammatory response in plaque rupture, which is absent in plaque erosion. Among the key differentially expressed proteins is interleukin-6 (IL-6; p<0.001), a protein crucially implicated in atherosclerosis and plaque destabilization. Surprisingly, patients with stable CAD show a T-cell- and proteomic profile largely similar to plaque rupture, while erosion is distinct from both.

Conclusion: For the first time, this study presents broad phenotypic and functional characterization of the inflammatory- and T-cell response in different pathophysiologies of ACS. Plaque rupture and stable CAD host a proinflammatory, T_H1-dominated response, which is absent in plaque erosion. This points to plaque erosion as a clearly different disease entity.  Inflammation may be a more prominent disease driver in patients with plaque rupture that could have implications for the personalized theraeputic management of these patients.