title: Autoantibodies targeting AT1 receptor from patients with acute coronary syndrome upregulate proinflammatory cytokines expression in endothelial cells involving NF-κB pathway.
abstract: Our study intended to prove whether agonistic autoantibodies to angiotensin II type 1 receptor (AT1-AAs) exist in patients with coronary heart disease (CHD) and affect the human endothelial cell (HEC) by upregulating proinflammatory cytokines expression involved in NF-κB pathway. Antibodies were determined by chronotropic responses of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists (valsartan and AT1-EC2) as described previously. Interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemotactic protein-1 (MCP-1) expression were improved at both mRNA and protein levels in HEC, while NF-κB in the DNA level was improved detected by electrophoretic mobility shift assays (EMSA). These improvements could be inhibited by specific AT1 receptor blocker valsartan, NF-κB blocker pyrrolidine dithiocarbamate (PDTC), and specific short peptides from the second extracellular loop of AT1 receptor. These results suggested that AT1-AAs, via the AT1 receptor, induce expression of proinflammatory cytokines involved in the activation of NF-κB. AT1-AAs may play a great role in the pathogenesis of the acute coronary syndrome by mediating vascular inflammatory effects involved in the NF-κB pathway.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, China.
authors.forename: Weijuan
authors.initials: W
authors.lastname: Li
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, China.
authors.forename: Yaoqi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, China.
authors.forename: Songhai
authors.initials: S
authors.lastname: Li
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, China.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Liao
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, China.
authors.forename: Zihua
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, China.
authors.forename: Qiutang
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430022, China.
authors.forename: Yumiao
authors.initials: Y
authors.lastname: Wei
mesh_terms: D054058:Acute Coronary Syndrome / Q000276:immunology*; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001323:Autoantibodies / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists / Q000737:chemistry / Q000276:immunology; D013859:Thiocarbamates / Q000494:pharmacology; D000068756:Valsartan / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D057911:Angiotensin Receptor Antagonists; D001323:Autoantibodies; D001324:Autoantigens; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D015850:Interleukin-6; D016328:NF-kappa B; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D013859:Thiocarbamates; D019010:Vascular Cell Adhesion Molecule-1; C066229:prolinedithiocarbamate; D000068756:Valsartan; D011392:Proline