title: Endothelial microparticles are increased in congenital heart diseases and contribute to endothelial dysfunction.
abstract: We previously demonstrated that endothelial microparticles (EMPs) are increased in mitral valve diseases and impair valvular endothelial cell function. Perioperative systemic inflammation is an important risk factor and complication of cardiac surgery. In this study, we investigate whether EMPs increase in congenital heart diseases to promote inflammation and endothelial dysfunction.
  
  
  
  The level of plasma EMPs in 20 patients with atrial septal defect (ASD), 23 patients with ventricular septal defect (VSD), and 30 healthy subjects were analyzed by flow cytometry. EMPs generated from human umbilical vascular endothelial cells (HUVECs) were injected into C57BL6 mice, or cultured with HUVECs without or with siRNAs targeting P38 MAPK. The expression and/or phosphorylation of endothelial nitric oxide synthase (eNOS), P38 MAPK, and caveolin-1 in mouse heart and/or in cultured HUVECs were determined. We evaluated generation of nitric oxide (NO) in mouse hearts, and levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cultured HUVECs and in mice.
  
  
  
  EMPs were significantly elevated in patients with ASD and VSD, especially in those with pulmonary hypertension when compared with controls. EMPs increased caveolin-1 expression and P38 MAPK phosphorylation and decreased eNOS phosphorylation and NO production in mouse hearts. EMPs stimulated P38 MAPK expression, TNF-α and IL-6 production, which were all inhibited by siRNAs targeting P38 MAPK in cultured HUVECs.
  
  
  
  EMPs were increased in adult patients with congenital heart diseases and may contribute to increased inflammation leading to endothelial dysfunction via P38 MAPK-dependent pathways. This novel data provides a potential therapeutic target to address important complications of surgery of congenial heart disease.
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, 510080, People's Republic of China.|The Key Laboratory of Assisted Circulation, Ministry of Health, Guangzhou, 510080, People's Republic of China.|National and Guangdong Province Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, People's Republic of China.
authors.forename: Ze-Bang
authors.initials: ZB
authors.lastname: Lin
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, 510080, People's Republic of China.|The Key Laboratory of Assisted Circulation, Ministry of Health, Guangzhou, 510080, People's Republic of China.|National and Guangdong Province Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, People's Republic of China.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Ci
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, 510080, People's Republic of China.|The Key Laboratory of Assisted Circulation, Ministry of Health, Guangzhou, 510080, People's Republic of China.|National and Guangdong Province Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, 510080, People's Republic of China.|The Key Laboratory of Assisted Circulation, Ministry of Health, Guangzhou, 510080, People's Republic of China.|National and Guangdong Province Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, People's Republic of China.
authors.forename: Tian-Pu
authors.initials: TP
authors.lastname: Cheng
authors.affiliation: Department of Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
authors.forename: Dong-Hong
authors.initials: DH
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou, 510080, People's Republic of China.|Guangzhou Institute of Respiratory Disease, Guangzhou, 510080, People's Republic of China.|The First Affiliated Hospital of Guangzhou Medical University Guangzhou, Guangzhou, 510120, People's Republic of China.
authors.forename: Yan-Sheng
authors.initials: YS
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou, 510080, People's Republic of China.|Guangzhou Institute of Respiratory Disease, Guangzhou, 510080, People's Republic of China.|The First Affiliated Hospital of Guangzhou Medical University Guangzhou, Guangzhou, 510120, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, 510080, People's Republic of China.|The Key Laboratory of Assisted Circulation, Ministry of Health, Guangzhou, 510080, People's Republic of China.|National and Guangdong Province Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, People's Republic of China.
authors.forename: Hao-Xiang
authors.initials: HX
authors.lastname: Yuan
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, 510080, People's Republic of China.|The Key Laboratory of Assisted Circulation, Ministry of Health, Guangzhou, 510080, People's Republic of China.|National and Guangdong Province Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, People's Republic of China.
authors.forename: Hua-Ming
authors.initials: HM
authors.lastname: Li
authors.affiliation: Division of Hypertension and Vascular Diseases, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, 510080, People's Republic of China.|The Key Laboratory of Assisted Circulation, Ministry of Health, Guangzhou, 510080, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, 510080, People's Republic of China.|The Key Laboratory of Assisted Circulation, Ministry of Health, Guangzhou, 510080, People's Republic of China.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Wang
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, 510080, People's Republic of China.|The Key Laboratory of Assisted Circulation, Ministry of Health, Guangzhou, 510080, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Hypertension and Vascular Diseases, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.|The Key Laboratory of Assisted Circulation, Ministry of Health, Guangzhou, 510080, People's Republic of China.|National and Guangdong Province Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, People's Republic of China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Ou
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou, 510080, People's Republic of China. oujs@mail.sysu.edu.cn.|The Key Laboratory of Assisted Circulation, Ministry of Health, Guangzhou, 510080, People's Republic of China. oujs@mail.sysu.edu.cn.|National and Guangdong Province Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, People's Republic of China. oujs@mail.sysu.edu.cn.|Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, 510080, People's Republic of China. oujs@mail.sysu.edu.cn.
authors.forename: Jing-Song
authors.initials: JS
authors.lastname: Ou
mesh_terms: D000328:Adult; D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D003710:Demography; D015150:Echocardiography, Doppler; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Congenital heart disease; Endothelial microparticles; Endothelial nitric oxide synthase; Inflammation; P38 MAPK pathway