Elevated endothelial microparticles induce inflammation to impair endothelial function in patients with congenital heart diseases

Objective We have demonstrated that endothelial microparticles (EMPs) increased in mitral valve diseases and impaired valvular endothelial cells function. Inflammation is one of the major risk factors in cardiac surgery. In this study, we investigate whether EMPs increase in congenital heart diseases and the effects of EMPs on inflammation and endothelial function. Methods The level of plasma EMPs in 20 patients with atrial septal defect (ASD), 23 patients with ventricular septal defect (VSD), and in 30 healthy subjects were analyzed by flow cytometry. EMPs generated from human umbilical vascular endothelial cells (HUVECs) were injected into C57BL6 mice for 6 hours, or cultured with HUVECs with/without P38 MAPK siRNAs. The expression and/or phosphorylation of endothelial nitric oxide synthase (eNOS), P38 and caveolin‐1 in mice heart and/or cultured HUVECs were determined. The nitric oxide (NO) generation in mice hearts was measured. The production of tumor necrosis factor‐a (TNF‐a) and interleukin (IL)‐6 in cultured HUVECs were detected. Results EMPs were significantly elevated in patients with ASD and VSD, especially in those with pulmonary hypertension. EMPs increased caveolin‐1 expression and P38 phosphorylation, decreased eNOS phosphorylation and NO production in hearts. EMPs stimulated P38 expression and TNF‐a and IL‐6 release, which could be inhibited by P38 MAPK siRNAs in cultured HUVECs. Conclusions Our study demonstrated that EMPs were increased in patients with congenital heart diseases. The increased of EMPs could induce inflammation to impair endothelial function. P38 MAPK pathway may play a vital role in EMPs induced inflammation and provide a therapeutic target. Support or Funding Information This study was supported by the National Natural Science Foundation of China (81170271, 81370370 and Distinguished Young Scholar 81325001), the Changjiang Scholars Program from Ministry of Education of China, the Guangdong Pearl River Scholars Program, 973 project (2009CB522104) and International Cooperation Project (2015DFA31070) from the Ministry of Science and Technology of China, Guangdong Natural Science Fund Committee, China (2015A030312009), Sun Yat‐Sen University Clinical Research 5010 Program; Program of National Key Clinical Specialties, the Science and Technology Research for the Returned Overseas Chinese Scholars from Ministry of Human Resources and Social Security of China (2011).