Role of Circulating Microparticles in Impairing Endothelial Function and Activating Oxidative Stress Is Related to No-Reflow in STEMI.

OBJECTIVE

Patients with ST-segment elevation myocardial infarction (STEMI) frequently experience no-reflow (NRF) during percutaneous coronary intervention (PCI). Nevertheless, the pathogenesis of NRF involves multiple factors and has not been fully elucidated to date. Given that endothelial dysfunction, inflammation, and oxidative stress are jointly implicated in both MP-related processes and NRF occurrence, this study was performed to explore the potential role of circulating microparticles (MPs) in the development of NRF.

METHODS

MPs were isolated from healthy subjects (n = 30), patients with angina and negative coronary angiography (control, n = 30), and STEMI patients with (n = 30) or without NRF (n = 30). The effects of MPs on endothelium-dependent vasodilatation, the expression of caveolin-1 and endothelial nitric oxide synthase (eNOS), and the production of nitric oxide (NO), superoxide anion (O2 •-), and intercellular adhesion molecule 1 (ICAM-1) were detected in mice. Furthermore, we examined the effects of MPs on the proliferation and endothelial tube formation of human coronary artery endothelial cells (HCAECs), with or without NG-nitro-L-arginine methyl ester (L-NAME) preincubation.

RESULTS

Compared with controls and healthy subjects, circulating MP levels were significantly higher in STEMI patients and were further elevated in STEMI patients with NRF. MPs isolated from NRF patients impaired endothelial-dependent vasodilatation, decreased the expression of phosphorylated eNOS at Ser1177, reduced NO production, HCAECs proliferation, and endothelial tube formation, but upregulated the expression of caveolin-1 and phosphorylated eNOS at Thr495, and increased the generation of O2 •- and ICAM-1. The effects of MPs on HCAECs were partially blocked by L-NAME.

CONCLUSIONS

Circulating MPs are associated with NRF in the clinical context and induce endothelial dysfunction in experimental models. Our findings provide new insight into the underlying molecular mechanisms of NRF in STEMI in experimental models.