SUV39H1 Inhibits Angiogenesis in Limb Ischemia of Mice
Peripheral arterial disease (PAD), characterized by atherosclerosis of the peripheral arteries or even amputation, has threatened public life and health. However, the underlying mechanism remains largely obscure. SUV39H1, a histone methyltransferase, could specifically methylate lysine 9 of histone...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2023-10-01
|
| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/09636897231198167 |
| _version_ | 1797663041624473600 |
|---|---|
| author | Wenhao Niu Wenyue Cao Feng Wu Chun Liang |
| author_facet | Wenhao Niu Wenyue Cao Feng Wu Chun Liang |
| author_sort | Wenhao Niu |
| collection | DOAJ |
| description | Peripheral arterial disease (PAD), characterized by atherosclerosis of the peripheral arteries or even amputation, has threatened public life and health. However, the underlying mechanism remains largely obscure. SUV39H1, a histone methyltransferase, could specifically methylate lysine 9 of histone H3 and act as a repressor in transcriptional activity. The study aimed to investigate the role of SUV39H1 in limb ischemia. C57BL/6 male mice were randomly divided into Sham or Model groups to investigate the expression of SUV39H1 in the ischemic limbs. Then, pharmaceutical inhibition or genetic deletion of SUV39H1 in the limb ischemia mice model was performed to confirm its effect on limb ischemia. The blood perfusion was quantified by laser speckle contrast imaging (LSCI). Capillary density and muscle edema were measured by CD31 immunohistochemical staining and HE staining. The expressions of SUV39H1 and Catalase were confirmed by western blot. Transcriptome sequencing of siSUV39H1 in human umbilical vein endothelial cells (HUVECs) was used to explore the regulation mechanism of SUV39H1 on angiogenesis. The results showed that SUV39H1 was highly expressed in the ischemic muscle tissue of the mice. Pharmaceutical inhibition or genetic deletion of SUV39H1 significantly improved blood perfusion, capillary density, and angiogenesis in ischemic muscle tissue. Cell experiments showed that SUV39H1 knockdown promoted cell migration, tube formation, and mitochondrial membrane potential in endothelial cells under oxidative stress. The transcriptome sequencing results unmasked mechanisms of the regulation of angiogenesis induced by SUV39H1. Finally, Salvianolic acid B and Astragaloside IV were identified as potential drug candidates for the improvement of endothelial function by repressing SUV39H1. Our study reveals a new mechanism in limb ischemia. Targeting SUV39H1 could improve endothelial dysfunction and thus prevent limb ischemia. |
| first_indexed | 2024-03-11T19:07:53Z |
| format | Article |
| id | doaj.art-0cfcae95c86747019e22566959435a5e |
| institution | Directory Open Access Journal |
| issn | 1555-3892 |
| language | English |
| last_indexed | 2024-03-11T19:07:53Z |
| publishDate | 2023-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-0cfcae95c86747019e22566959435a5e2023-10-10T00:03:23ZengSAGE PublishingCell Transplantation1555-38922023-10-013210.1177/09636897231198167SUV39H1 Inhibits Angiogenesis in Limb Ischemia of MiceWenhao Niu0Wenyue Cao1Feng Wu2Chun Liang3Department of Cardiology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, ChinaDepartment of Ultrasonography, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Cardiology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, ChinaPeripheral arterial disease (PAD), characterized by atherosclerosis of the peripheral arteries or even amputation, has threatened public life and health. However, the underlying mechanism remains largely obscure. SUV39H1, a histone methyltransferase, could specifically methylate lysine 9 of histone H3 and act as a repressor in transcriptional activity. The study aimed to investigate the role of SUV39H1 in limb ischemia. C57BL/6 male mice were randomly divided into Sham or Model groups to investigate the expression of SUV39H1 in the ischemic limbs. Then, pharmaceutical inhibition or genetic deletion of SUV39H1 in the limb ischemia mice model was performed to confirm its effect on limb ischemia. The blood perfusion was quantified by laser speckle contrast imaging (LSCI). Capillary density and muscle edema were measured by CD31 immunohistochemical staining and HE staining. The expressions of SUV39H1 and Catalase were confirmed by western blot. Transcriptome sequencing of siSUV39H1 in human umbilical vein endothelial cells (HUVECs) was used to explore the regulation mechanism of SUV39H1 on angiogenesis. The results showed that SUV39H1 was highly expressed in the ischemic muscle tissue of the mice. Pharmaceutical inhibition or genetic deletion of SUV39H1 significantly improved blood perfusion, capillary density, and angiogenesis in ischemic muscle tissue. Cell experiments showed that SUV39H1 knockdown promoted cell migration, tube formation, and mitochondrial membrane potential in endothelial cells under oxidative stress. The transcriptome sequencing results unmasked mechanisms of the regulation of angiogenesis induced by SUV39H1. Finally, Salvianolic acid B and Astragaloside IV were identified as potential drug candidates for the improvement of endothelial function by repressing SUV39H1. Our study reveals a new mechanism in limb ischemia. Targeting SUV39H1 could improve endothelial dysfunction and thus prevent limb ischemia.https://doi.org/10.1177/09636897231198167 |
| spellingShingle | Wenhao Niu Wenyue Cao Feng Wu Chun Liang SUV39H1 Inhibits Angiogenesis in Limb Ischemia of Mice Cell Transplantation |
| title | SUV39H1 Inhibits Angiogenesis in Limb Ischemia of Mice |
| title_full | SUV39H1 Inhibits Angiogenesis in Limb Ischemia of Mice |
| title_fullStr | SUV39H1 Inhibits Angiogenesis in Limb Ischemia of Mice |
| title_full_unstemmed | SUV39H1 Inhibits Angiogenesis in Limb Ischemia of Mice |
| title_short | SUV39H1 Inhibits Angiogenesis in Limb Ischemia of Mice |
| title_sort | suv39h1 inhibits angiogenesis in limb ischemia of mice |
| url | https://doi.org/10.1177/09636897231198167 |
| work_keys_str_mv | AT wenhaoniu suv39h1inhibitsangiogenesisinlimbischemiaofmice AT wenyuecao suv39h1inhibitsangiogenesisinlimbischemiaofmice AT fengwu suv39h1inhibitsangiogenesisinlimbischemiaofmice AT chunliang suv39h1inhibitsangiogenesisinlimbischemiaofmice |