The main findings of the present study were as follows; Eosinophil fraction in the aspirated thrombi was significantly higher in Epoxomicin Proteasome inhibitor patients with DES VLST as compared with those with EST and LST; Eosinophil fraction in the aspirated thrombi in patients with DES VLST was significantly higher in patients with PSS and/or ISA as compared with those without PSS or ISA; and Evidences for fragments of atherosclerotic plaques were relatively uncommon in patients with DES VLST. IVUS studies after SES implantation revealed a higher incidence of ISA with DES compared with BMS. From the several IVUS studies, the prevalence of ISA at the time of VLST was high. In the present study, we found PSS and/or ISA in 12 out of 24 lesions of VLST. The prevalence of PSS and ISA were consistent with the previous reports. The RESTART was a Japanese large registry of SES-associated ST, and the angiographic substudy demonstrated that PSS was present in 34.1% of patients with SES-associated VLST. Recently, Imai et al. reported that PSS was found within 12 months after SES implantation in 194 lesions out of 7838 lesions, and cumulative incidence of VLST at 4 years was significantly higher in lesions with PSS as compared with those without PSS. Therefore, ISA and PSS might represent abnormal vessel wall responses to DES, which predisposed to VLST. However, the pathophysiologic mechanisms of ISA and PSS formation leading to VLST have not been yet adequately clarified. Cook et al. reported that the number of eosinophils in the aspirated thrombi at the time of DES VLST correlated with the extent of stent malapposition in relatively small number of patients. In the current study evaluating larger number of patients with DES VLST, eosinophil fraction in the aspirated thrombi was significantly higher in patients with VLST as compared with those with EST and LST. Furthermore, eosinophil fraction in the aspirated thrombi in patients with DES VLST was significantly higher in patients with PSS and/or ISA as compared with those without PSS or ISA. Higher eosinophil fraction in the aspirated thrombi might be attributable to localized hypersensitivity vasculitis. Indeed, previous human pathologic studies suggested that hypersensitivity vasculitis in response to SES caused intimal damage leading to vascular surface defect with PSS and/or ISA, and long-lasting severe hypersensitivity vasculitis might lead to further medial disruption and destruction of vessel wall with aneurysmal dilatation. Localized hypersensitivity vasculitis was a major underlying mechanisms of VLST in patients with positive remodeling and mal-apposition of the stent struts. In contrast, there was a postmortem case report demonstrating late ISA by focal positive vessel remodeling caused by medial necrosis without hypersensitivity reaction. Medial necrosis with medial smooth muscle cell depletion could also be a possible mechanism for positive remodeling and mal-apposition of the stent struts. The mechanisms of DES VLST could be multi-factorial. In a human postmortem pathologic study, neoatherosclerosis was a frequent finding in the DEStreated lesions and occurred earlier than in the BMS-treated lesions.