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Local Augmented Angiotensinogen Secreted from Apoptotic Vascular Endothelial Cells Is a Vital Mediator of Vascular Remodelling
- Source :
- PLoS ONE, Vol 10, Iss 7, p e0132583 (2015), PLoS ONE
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 2015.
-
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.
- Subjects :
- medicine.medical_specialty
Intimal hyperplasia
Vascular smooth muscle
MAP Kinase Signaling System
Myocytes, Smooth Muscle
Angiotensinogen
lcsh:Medicine
Angiotensin-Converting Enzyme Inhibitors
Apoptosis
Peptidyl-Dipeptidase A
Vascular Remodeling
Biology
Muscle, Smooth, Vascular
Umbilical vein
Cell Line
Vascular remodelling in the embryo
Mice
Lisinopril
Internal medicine
Renin–angiotensin system
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
lcsh:Science
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Multidisciplinary
Angiotensin II
lcsh:R
medicine.disease
Rats
Losartan
Endocrinology
ACE inhibitor
cardiovascular system
lcsh:Q
Research Article
medicine.drug
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....3a74b2dd2c5e33872cc08fecec2580ea