Valsartan Attenuated Homocysteine-Induced Impaired Autophagy and ER Stress in Human Umbilical Vein Endothelial Cells
Hyperhomocysteinemia is a risk factor for various cardiovascular diseases. However, the mechanism underlying homocysteine- (Hcy-) induced vascular injury remains unclear. The purpose of the present study was to examine a potential mechanism by which Hcy induced injury in human umbilical vascular end...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-01-01
|
| Series: | Cardiovascular Therapeutics |
| Online Access: | http://dx.doi.org/10.1155/2023/8817431 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849308661316321280 |
|---|---|
| author | Xinyan Wu Ani Wang Long Xu Meng Li Qingxian Zhai Weidong Wang Chunling Li Lizi Jin |
| author_facet | Xinyan Wu Ani Wang Long Xu Meng Li Qingxian Zhai Weidong Wang Chunling Li Lizi Jin |
| author_sort | Xinyan Wu |
| collection | DOAJ |
| description | Hyperhomocysteinemia is a risk factor for various cardiovascular diseases. However, the mechanism underlying homocysteine- (Hcy-) induced vascular injury remains unclear. The purpose of the present study was to examine a potential mechanism by which Hcy induced injury in human umbilical vascular endothelial cells (HUVEC). The protein abundance of autophagy-related markers was markedly decreased after Hcy treatment, which was associated with endoplasmic reticulum (ER) stress and apoptosis in HUVECs. Protein expression level of angiotensin II type 1 receptor (AT1 receptor) was dramatically increased in response to Hcy. Valsartan, an AT1 receptor blocker, improved autophagy and prevented ER stress and apoptosis in HUVECs treated with Hcy. Consistent with this, silence of AT1 receptor with siRNA decreased the protein abundance of ER stress markers, prevented apoptosis, and promoted autophagy in HUVECs. Inhibition or knockdown of AT1 receptor was shown to be associated with suppression of p-GSK3β/GSK3β-p-mTOR/mTOR signaling pathway. Additionally, inhibition of autophagy by 3-MA aggravated Hcy-induced apoptosis, while amelioration of ER stress by 4-PBA prevented Hcy-induced injury in HUVECs. Hcy-induced HUVEC injury was likely attributed to AT1 receptor activation, leading to impaired autophagy, ER stress, and apoptosis. |
| format | Article |
| id | doaj-art-0ece529d354a4c3bbb858b074e1ea765 |
| institution | Kabale University |
| issn | 1755-5922 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cardiovascular Therapeutics |
| spelling | doaj-art-0ece529d354a4c3bbb858b074e1ea7652025-08-20T03:54:24ZengWileyCardiovascular Therapeutics1755-59222023-01-01202310.1155/2023/8817431Valsartan Attenuated Homocysteine-Induced Impaired Autophagy and ER Stress in Human Umbilical Vein Endothelial CellsXinyan Wu0Ani Wang1Long Xu2Meng Li3Qingxian Zhai4Weidong Wang5Chunling Li6Lizi Jin7Department of CardiologyDepartment of CardiologyDepartment of PhysiologyDepartment of PhysiologyDepartment of PathophysiologyDepartment of PathophysiologyDepartment of PhysiologyDepartment of CardiologyHyperhomocysteinemia is a risk factor for various cardiovascular diseases. However, the mechanism underlying homocysteine- (Hcy-) induced vascular injury remains unclear. The purpose of the present study was to examine a potential mechanism by which Hcy induced injury in human umbilical vascular endothelial cells (HUVEC). The protein abundance of autophagy-related markers was markedly decreased after Hcy treatment, which was associated with endoplasmic reticulum (ER) stress and apoptosis in HUVECs. Protein expression level of angiotensin II type 1 receptor (AT1 receptor) was dramatically increased in response to Hcy. Valsartan, an AT1 receptor blocker, improved autophagy and prevented ER stress and apoptosis in HUVECs treated with Hcy. Consistent with this, silence of AT1 receptor with siRNA decreased the protein abundance of ER stress markers, prevented apoptosis, and promoted autophagy in HUVECs. Inhibition or knockdown of AT1 receptor was shown to be associated with suppression of p-GSK3β/GSK3β-p-mTOR/mTOR signaling pathway. Additionally, inhibition of autophagy by 3-MA aggravated Hcy-induced apoptosis, while amelioration of ER stress by 4-PBA prevented Hcy-induced injury in HUVECs. Hcy-induced HUVEC injury was likely attributed to AT1 receptor activation, leading to impaired autophagy, ER stress, and apoptosis.http://dx.doi.org/10.1155/2023/8817431 |
| spellingShingle | Xinyan Wu Ani Wang Long Xu Meng Li Qingxian Zhai Weidong Wang Chunling Li Lizi Jin Valsartan Attenuated Homocysteine-Induced Impaired Autophagy and ER Stress in Human Umbilical Vein Endothelial Cells Cardiovascular Therapeutics |
| title | Valsartan Attenuated Homocysteine-Induced Impaired Autophagy and ER Stress in Human Umbilical Vein Endothelial Cells |
| title_full | Valsartan Attenuated Homocysteine-Induced Impaired Autophagy and ER Stress in Human Umbilical Vein Endothelial Cells |
| title_fullStr | Valsartan Attenuated Homocysteine-Induced Impaired Autophagy and ER Stress in Human Umbilical Vein Endothelial Cells |
| title_full_unstemmed | Valsartan Attenuated Homocysteine-Induced Impaired Autophagy and ER Stress in Human Umbilical Vein Endothelial Cells |
| title_short | Valsartan Attenuated Homocysteine-Induced Impaired Autophagy and ER Stress in Human Umbilical Vein Endothelial Cells |
| title_sort | valsartan attenuated homocysteine induced impaired autophagy and er stress in human umbilical vein endothelial cells |
| url | http://dx.doi.org/10.1155/2023/8817431 |
| work_keys_str_mv | AT xinyanwu valsartanattenuatedhomocysteineinducedimpairedautophagyanderstressinhumanumbilicalveinendothelialcells AT aniwang valsartanattenuatedhomocysteineinducedimpairedautophagyanderstressinhumanumbilicalveinendothelialcells AT longxu valsartanattenuatedhomocysteineinducedimpairedautophagyanderstressinhumanumbilicalveinendothelialcells AT mengli valsartanattenuatedhomocysteineinducedimpairedautophagyanderstressinhumanumbilicalveinendothelialcells AT qingxianzhai valsartanattenuatedhomocysteineinducedimpairedautophagyanderstressinhumanumbilicalveinendothelialcells AT weidongwang valsartanattenuatedhomocysteineinducedimpairedautophagyanderstressinhumanumbilicalveinendothelialcells AT chunlingli valsartanattenuatedhomocysteineinducedimpairedautophagyanderstressinhumanumbilicalveinendothelialcells AT lizijin valsartanattenuatedhomocysteineinducedimpairedautophagyanderstressinhumanumbilicalveinendothelialcells |