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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

SS of HUVECs and VSMCs.(A) Effect of 24-h SS on cell morphology and density of HUVECs and VSMCs (right panel). (B) Cell viability was assessed after SS in HUVECs (at 3, 6, and 12 h) and in SMCs (at 6 and 12 h). The mean percentages of at least 3 independent experiments are represented in both cells. The square insert indicates the magnified area. ***P < 0.001 in comparison to cells without SS. Data are expressed as the mean ± SE and are representative of 3 experiments.
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pone.0132583.g001: SS of HUVECs and VSMCs.(A) Effect of 24-h SS on cell morphology and density of HUVECs and VSMCs (right panel). (B) Cell viability was assessed after SS in HUVECs (at 3, 6, and 12 h) and in SMCs (at 6 and 12 h). The mean percentages of at least 3 independent experiments are represented in both cells. The square insert indicates the magnified area. ***P < 0.001 in comparison to cells without SS. Data are expressed as the mean ± SE and are representative of 3 experiments.

Mentions: To imitate the condition that causes cell apoptosis in vitro, HUVECs and A7r5 VSMCs were starved using a serum-free medium. Both HUVECs and VSMCs underwent apoptosis or died after 24 h of SS (Fig 1A). Furthermore, the cell viability of HUVECs decreased rapidly to 65% after the cells underwent SS for 3 h. The cell viability of VSMCs also decreased after SS treatment (Fig 1B).


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)

SS of HUVECs and VSMCs.(A) Effect of 24-h SS on cell morphology and density of HUVECs and VSMCs (right panel). (B) Cell viability was assessed after SS in HUVECs (at 3, 6, and 12 h) and in SMCs (at 6 and 12 h). The mean percentages of at least 3 independent experiments are represented in both cells. The square insert indicates the magnified area. ***P < 0.001 in comparison to cells without SS. Data are expressed as the mean ± SE and are representative of 3 experiments.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132583.g001: SS of HUVECs and VSMCs.(A) Effect of 24-h SS on cell morphology and density of HUVECs and VSMCs (right panel). (B) Cell viability was assessed after SS in HUVECs (at 3, 6, and 12 h) and in SMCs (at 6 and 12 h). The mean percentages of at least 3 independent experiments are represented in both cells. The square insert indicates the magnified area. ***P < 0.001 in comparison to cells without SS. Data are expressed as the mean ± SE and are representative of 3 experiments.
Mentions: To imitate the condition that causes cell apoptosis in vitro, HUVECs and A7r5 VSMCs were starved using a serum-free medium. Both HUVECs and VSMCs underwent apoptosis or died after 24 h of SS (Fig 1A). Furthermore, the cell viability of HUVECs decreased rapidly to 65% after the cells underwent SS for 3 h. The cell viability of VSMCs also decreased after SS treatment (Fig 1B).

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