Mechanism of adenosine monophosphate-activated protein kinase promoting lower extremity varicose veins development via cytoskeletal dynamics
Abstract Objective This study aimed to investigate the potential involvement of 5'-AMP-activated protein kinase (AMPK) in the pathogenesis of lower-extremity varicose veins (VV). Methods In this study, 8 patients with CEAP stage C6 chronic venous disease and 8 age-matched healthy controls were...
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BMC
2025-05-01
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| Series: | BMC Cardiovascular Disorders |
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| Online Access: | https://doi.org/10.1186/s12872-025-04821-6 |
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| author | Yongmei Zhang Zhinan Ju Kanghui Dai Liqun Wan Guangmao Zhou Yanchun Ji Jiehua Qiu |
| author_facet | Yongmei Zhang Zhinan Ju Kanghui Dai Liqun Wan Guangmao Zhou Yanchun Ji Jiehua Qiu |
| author_sort | Yongmei Zhang |
| collection | DOAJ |
| description | Abstract Objective This study aimed to investigate the potential involvement of 5'-AMP-activated protein kinase (AMPK) in the pathogenesis of lower-extremity varicose veins (VV). Methods In this study, 8 patients with CEAP stage C6 chronic venous disease and 8 age-matched healthy controls were prospectively recruited to collect samples for preparation of subsequent experiments.None of the patients included in the molecular analyses were diagnosed with diabetes, as our analysis of 73,313 patients demonstrated that diabetes is generally not associated with VV. Western blotting was employed to quantify the levels of p-AMPK, G-actin, p-tubulin, p-HSP20, and 14–3-3 proteins in each sample. Results Epidemiological analyses revealed 5,262 patients with VVs among 714,789 inpatients. Of these patients, only 351 VV patients were diagnosed with type 2 DM, while 4,911 were not diagnosed with DM. Higher levels of AMPK activation were evident in VV samples in molecular analyses, with the p-AMPK level in the VV group being 1.98 ± 0.56 times higher than that in the NV group (n = 3, P < 0.001). G-actin levels in VV samples were additionally 2.14 ± 0.60 times higher than those in NV samples (n = 3, P < 0.001). Increased cofilin activation was also observed in VV samples, as evidenced by p-cofilin levels in the VV group that were 0.63 ± 0.10 times those in the NV group (n = 3, P < 0.001), with VV samples additionally exhibiting p-HSP20 levels that were 2.02 ± 0.59 times higher than those in NV samples (n = 3, P < 0.001). Conclusion These results suggest that AMPK Is likely to be involved lower extremity VV development, potentially by inducing vasodilation through the dysregulation of F-actin cytoskeletal dynamics in VSMCs, increasing cofilin activation, the displacement of which from 14–3-3 can lead to dephosphorylation mediated by HSP20,and then causes its dephosphorylation and increased activity, and thereby reducing cytoskeletal actin homeostasis and promoting vascular relaxation.These findings elucidate the possible regulatory role of AMPK phosphorylation in vein wall degeneration and provide a theoretical basis for further studies. |
| format | Article |
| id | doaj-art-ffc6accadda442b39d6099f1cd8421da |
| institution | OA Journals |
| issn | 1471-2261 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | BMC Cardiovascular Disorders |
| spelling | doaj-art-ffc6accadda442b39d6099f1cd8421da2025-08-20T01:59:56ZengBMCBMC Cardiovascular Disorders1471-22612025-05-012511810.1186/s12872-025-04821-6Mechanism of adenosine monophosphate-activated protein kinase promoting lower extremity varicose veins development via cytoskeletal dynamicsYongmei Zhang0Zhinan Ju1Kanghui Dai2Liqun Wan3Guangmao Zhou4Yanchun Ji5Jiehua Qiu6Department of Clinical Laboratory, the Second Affiliated Hospital of Nanchang University, Nanchang Department of Vascular Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang Department of Vascular Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang Department of Vascular Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang Department of Vascular Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang Division of Medical Genetics and Genomics, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child HealthDepartment of Vascular Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang Abstract Objective This study aimed to investigate the potential involvement of 5'-AMP-activated protein kinase (AMPK) in the pathogenesis of lower-extremity varicose veins (VV). Methods In this study, 8 patients with CEAP stage C6 chronic venous disease and 8 age-matched healthy controls were prospectively recruited to collect samples for preparation of subsequent experiments.None of the patients included in the molecular analyses were diagnosed with diabetes, as our analysis of 73,313 patients demonstrated that diabetes is generally not associated with VV. Western blotting was employed to quantify the levels of p-AMPK, G-actin, p-tubulin, p-HSP20, and 14–3-3 proteins in each sample. Results Epidemiological analyses revealed 5,262 patients with VVs among 714,789 inpatients. Of these patients, only 351 VV patients were diagnosed with type 2 DM, while 4,911 were not diagnosed with DM. Higher levels of AMPK activation were evident in VV samples in molecular analyses, with the p-AMPK level in the VV group being 1.98 ± 0.56 times higher than that in the NV group (n = 3, P < 0.001). G-actin levels in VV samples were additionally 2.14 ± 0.60 times higher than those in NV samples (n = 3, P < 0.001). Increased cofilin activation was also observed in VV samples, as evidenced by p-cofilin levels in the VV group that were 0.63 ± 0.10 times those in the NV group (n = 3, P < 0.001), with VV samples additionally exhibiting p-HSP20 levels that were 2.02 ± 0.59 times higher than those in NV samples (n = 3, P < 0.001). Conclusion These results suggest that AMPK Is likely to be involved lower extremity VV development, potentially by inducing vasodilation through the dysregulation of F-actin cytoskeletal dynamics in VSMCs, increasing cofilin activation, the displacement of which from 14–3-3 can lead to dephosphorylation mediated by HSP20,and then causes its dephosphorylation and increased activity, and thereby reducing cytoskeletal actin homeostasis and promoting vascular relaxation.These findings elucidate the possible regulatory role of AMPK phosphorylation in vein wall degeneration and provide a theoretical basis for further studies.https://doi.org/10.1186/s12872-025-04821-6Lower extremity varicose veinAMPKCofilinHSP20VSMC |
| spellingShingle | Yongmei Zhang Zhinan Ju Kanghui Dai Liqun Wan Guangmao Zhou Yanchun Ji Jiehua Qiu Mechanism of adenosine monophosphate-activated protein kinase promoting lower extremity varicose veins development via cytoskeletal dynamics BMC Cardiovascular Disorders Lower extremity varicose vein AMPK Cofilin HSP20 VSMC |
| title | Mechanism of adenosine monophosphate-activated protein kinase promoting lower extremity varicose veins development via cytoskeletal dynamics |
| title_full | Mechanism of adenosine monophosphate-activated protein kinase promoting lower extremity varicose veins development via cytoskeletal dynamics |
| title_fullStr | Mechanism of adenosine monophosphate-activated protein kinase promoting lower extremity varicose veins development via cytoskeletal dynamics |
| title_full_unstemmed | Mechanism of adenosine monophosphate-activated protein kinase promoting lower extremity varicose veins development via cytoskeletal dynamics |
| title_short | Mechanism of adenosine monophosphate-activated protein kinase promoting lower extremity varicose veins development via cytoskeletal dynamics |
| title_sort | mechanism of adenosine monophosphate activated protein kinase promoting lower extremity varicose veins development via cytoskeletal dynamics |
| topic | Lower extremity varicose vein AMPK Cofilin HSP20 VSMC |
| url | https://doi.org/10.1186/s12872-025-04821-6 |
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