Microparticles from ISR patients participate in vascular intimal hyperplasia by promoting oxidative stress, inflammation and adhesion through ERK and P38 pathways

Abstract

Abstract Objectives: Percutaneous coronary intervention (PCI) has become the most commonly used vascular reconstruction method for coronary atherosclerotic heart disease (CHD). However, In-stent restenosis (ISR) seriously affects the prognosis of PCI. Vascular intimal hyperplasia play key roles in ISR. Whether circulating microparticles (MPs) from ISR patients, which cause oxidative stress, inflammation and adhesion of vascular, participate in endothelial dysfunction and vascular intimal hyperplasia remains unclear. Methods: MPs were obtained from both healthy subjects (n=20) and coronary heart disease patients with (n=33) or without (n=33) ISR 1year after PCI. After testing MPs origins by flow cytometry. Affect of MPs (with or without inhibitor of mitogen activated protein kinase) on proliferation and migration , expression of Extracellular signal-related kinase (ERK), p38 mitogen activated protein kinase (P38) and c-Jun N-terminal kinases (JNK), generation of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in human coronary artery smooth muscle cells (HCASMCs) were determined. Results: Although MPs increased in patients with or without ISR compared with healthy subjects, there were no difference between patients with or without ISR in MPs concentration. Flow cytometry showed that both endothelial derived MPs (EMP) and platelet-derived MP (PMP) ratio expanded in patient group. MPs from patients without ISR stimulate HCASMCs proliferation and migration (which can be blocked partly by PD98059), increased phosphorylation of ERK and P38,but not JNK; increased ICAM-1 and VCAM-1 generation in HCASMCs (which can be blocked by SB20358 but not SP600125). All of these effects were strengthened by MPs from patients with ISR. Conclusions: MPs from ISR participate in vascular intimal hyperplasia, which play a key roles in ISR, by stimulating proliferation and migration, promoting oxidative stress, inflammation and adhesion through ERK and P38 pathway in HCASMCs. This may indicated a potential therapeutic target for ISR.