title: Local Augmented Angiotensinogen Secreted from Apoptotic Vascular Endothelial Cells Is a Vital Mediator of Vascular Remodelling.
abstract: Vascular remodelling is a critical vasculopathy found in atheromatous diseases and allograft failures. The local renin angiotensin system (RAS) has been implicated in vascular remodelling. However, the mechanisms by which the augmented local RAS is associated with the initial event of endothelial cell apoptosis in injured vasculature remain undefined. We induced the apoptosis of human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs) through serum starvation (SS). After the cells were subjected to SS, we found that the mRNA expression of angiotensinogen (AGT) was increased by >3-fold in HUVECs and by approximately 2.5-fold in VSMCs. In addition, the expression of angiotensin-converting enzyme (ACE) mRNA was increased in VSMCs but decreased to 50% in HUVECs during the same apoptotic process. Increases in the expression of AGT protein and angiotensin II (Ang II) were found in a serum-free medium conditioned by HUVECs (SSC). The increased Ang II was suppressed using lisinopril (an ACE inhibitor) treatment. Moreover, the activation of ERK1/2 induced by the SSC in VSMCs was also suppressed by losartan. In conclusion, we first demonstrated that the augmented AGT released from apoptotic endothelial cells acts as a vital progenitor of Ang II to accelerate vascular remodelling, and we suggest that blocking local augmented Ang II might be an effective strategy for restraining intimal hyperplasia.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shyh-Jong
authors.initials: SJ
authors.lastname: Wu
authors.affiliation: Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Soulez
authors.affiliation: Department of Occupational Safety and Hygiene, Fooyin University, Kaohsiung, Taiwan.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Yang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Chu
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shih-Chuan
authors.initials: SC
authors.lastname: Shih
authors.affiliation: Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM), Hôpital Notre Dame and Université de Montréal, Montréal, QC, Canada.
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Hébert
authors.affiliation: Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Mei-Chuan
authors.initials: MC
authors.lastname: Kuo
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ya-Ju
authors.initials: YJ
authors.lastname: Hsieh
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D017706:Lisinopril / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D066253:Vascular Remodeling
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000808:Angiotensinogen; D000804:Angiotensin II; D017706:Lisinopril; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D007703:Peptidyl-Dipeptidase A