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Local Augmented Angiotensinogen Secreted from Apoptotic Vascular Endothelial Cells Is a Vital Mediator of Vascular Remodelling.

Wu SJ, Soulez M, Yang YH, Chu CS, Shih SC, Hébert MJ, Kuo MC, Hsieh YJ - PLoS ONE (2015)

Bottom Line: 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.Increases in the expression of AGT protein and angiotensin II (Ang II) were found in a serum-free medium conditioned by HUVECs (SSC).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus

Apoptosis of ECs in an allograft vessel.Recipient and donor aortic sections stained for activated caspase-3 at 3 wk posttransplantation. Red arrows indicate activated caspase-3-positive cells; black arrows indicate fragmented and condensed DNA as well as apoptotic membrane blebbing of the endothelium. The square insert indicates the magnified area.
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pone.0132583.g002: Apoptosis of ECs in an allograft vessel.Recipient and donor aortic sections stained for activated caspase-3 at 3 wk posttransplantation. Red arrows indicate activated caspase-3-positive cells; black arrows indicate fragmented and condensed DNA as well as apoptotic membrane blebbing of the endothelium. The square insert indicates the magnified area.

Mentions: Neointima formation was found in a donor arterial segment of an allograft vessel, and fragmented and condensed nuclei and apoptotic EC blebbing were found in allogenic endothelia (Fig 2), in which the apoptotic ECs in the inner lining of the remodelling vessel were substantially stained with an activated caspase-3 antibody at 3 wk posttransplantation.


Local Augmented Angiotensinogen Secreted from Apoptotic Vascular Endothelial Cells Is a Vital Mediator of Vascular Remodelling.

Wu SJ, Soulez M, Yang YH, Chu CS, Shih SC, Hébert MJ, Kuo MC, Hsieh YJ - PLoS ONE (2015)

Apoptosis of ECs in an allograft vessel.Recipient and donor aortic sections stained for activated caspase-3 at 3 wk posttransplantation. Red arrows indicate activated caspase-3-positive cells; black arrows indicate fragmented and condensed DNA as well as apoptotic membrane blebbing of the endothelium. The square insert indicates the magnified area.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492977&req=5

pone.0132583.g002: Apoptosis of ECs in an allograft vessel.Recipient and donor aortic sections stained for activated caspase-3 at 3 wk posttransplantation. Red arrows indicate activated caspase-3-positive cells; black arrows indicate fragmented and condensed DNA as well as apoptotic membrane blebbing of the endothelium. The square insert indicates the magnified area.
Mentions: Neointima formation was found in a donor arterial segment of an allograft vessel, and fragmented and condensed nuclei and apoptotic EC blebbing were found in allogenic endothelia (Fig 2), in which the apoptotic ECs in the inner lining of the remodelling vessel were substantially stained with an activated caspase-3 antibody at 3 wk posttransplantation.

Bottom Line: 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.Increases in the expression of AGT protein and angiotensin II (Ang II) were found in a serum-free medium conditioned by HUVECs (SSC).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus