CAVIN-2 positively correlates with diabetic PAD and promotes LDL transcytosis by inhibiting eNOS activation

Objective Caveolae are closely linked to the onset and progression of atherosclerosis. The pivotal involvement of caveolin-1 (CAV1) within the caveolae in atherosclerosis development has been consistently supported. However, the potential contributions of additional caveolae proteins to atherosclero...

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Main Authors: Li Wang, Yi Song, Yan Shu, Baorui Xue, Fangyang Yu, Yao Yin, Ziyun Feng, Xiang Ma, Yulin Yao, Yangze Pan, Si Jin
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Annals of Medicine
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Online Access:https://www.tandfonline.com/doi/10.1080/07853890.2025.2457526
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author Li Wang
Yi Song
Yan Shu
Baorui Xue
Fangyang Yu
Yao Yin
Ziyun Feng
Xiang Ma
Yulin Yao
Yangze Pan
Si Jin
author_facet Li Wang
Yi Song
Yan Shu
Baorui Xue
Fangyang Yu
Yao Yin
Ziyun Feng
Xiang Ma
Yulin Yao
Yangze Pan
Si Jin
author_sort Li Wang
collection DOAJ
description Objective Caveolae are closely linked to the onset and progression of atherosclerosis. The pivotal involvement of caveolin-1 (CAV1) within the caveolae in atherosclerosis development has been consistently supported. However, the potential contributions of additional caveolae proteins to atherosclerosis necessitate further exploration. Therefore, this research aimed to afford clinical evidence linking CAVIN-2 to diabetic peripheral artery disease (PAD) and its role in low-density lipoprotein (LDL) transcytosis.Methods Blood samples were collected from a total of 115 participants, including 36 patients without diabetes (ND), 26 patients with type 2 diabetes mellitus (T2DM), and 53 patients with T2DM and PAD (DM-PAD). The plasma levels of CAV1, CAVIN-1, and CAVIN-2 were measured by ELISA. The correlation between CAV1, CAVIN-1, CAVIN-2, and diabetic PAD was examined using Spearman correlation analysis. The predictive effect of CAV1 and CAVIN-2 were analyzed by receiver operating characteristic (ROC) curves. Cellular experiments were used to investigate the effect and mechanism of CAVIN-2 on LDL transcytosis.Results Elevated CAV1 and CAVIN-2 levels were observed in T2DM and DM-PAD groups, with a positive correlation to DM-PAD and PAD severity. Both CAV1 and CAVIN-2 emerged as predictors of DM-PAD. In vitro, CAVIN-2 knockdown decreased LDL transcytosis, while CAVIN-2 overexpression increased it. Additionally, CAVIN-2 was found to inhibit eNOS activation and nitric oxide (NO) production, thereby promoting LDL transcytosis and atherosclerosis progression.Conclusion CAVIN-2 was positively correlated with DM-PAD and promoted LDL transcytosis through the inhibition of eNOS activation, contributing to atherosclerosis development. This study provided clinical evidence linking CAVIN-2 to diabetic PAD and suggested its potential as a biomarker for disease progression.
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spelling doaj-art-995311e1ed7d47cf91eef473566a07e62025-01-31T15:04:45ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602025-12-0157110.1080/07853890.2025.2457526CAVIN-2 positively correlates with diabetic PAD and promotes LDL transcytosis by inhibiting eNOS activationLi Wang0Yi Song1Yan Shu2Baorui Xue3Fangyang Yu4Yao Yin5Ziyun Feng6Xiang Ma7Yulin Yao8Yangze Pan9Si Jin10Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Endocrinology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaObjective Caveolae are closely linked to the onset and progression of atherosclerosis. The pivotal involvement of caveolin-1 (CAV1) within the caveolae in atherosclerosis development has been consistently supported. However, the potential contributions of additional caveolae proteins to atherosclerosis necessitate further exploration. Therefore, this research aimed to afford clinical evidence linking CAVIN-2 to diabetic peripheral artery disease (PAD) and its role in low-density lipoprotein (LDL) transcytosis.Methods Blood samples were collected from a total of 115 participants, including 36 patients without diabetes (ND), 26 patients with type 2 diabetes mellitus (T2DM), and 53 patients with T2DM and PAD (DM-PAD). The plasma levels of CAV1, CAVIN-1, and CAVIN-2 were measured by ELISA. The correlation between CAV1, CAVIN-1, CAVIN-2, and diabetic PAD was examined using Spearman correlation analysis. The predictive effect of CAV1 and CAVIN-2 were analyzed by receiver operating characteristic (ROC) curves. Cellular experiments were used to investigate the effect and mechanism of CAVIN-2 on LDL transcytosis.Results Elevated CAV1 and CAVIN-2 levels were observed in T2DM and DM-PAD groups, with a positive correlation to DM-PAD and PAD severity. Both CAV1 and CAVIN-2 emerged as predictors of DM-PAD. In vitro, CAVIN-2 knockdown decreased LDL transcytosis, while CAVIN-2 overexpression increased it. Additionally, CAVIN-2 was found to inhibit eNOS activation and nitric oxide (NO) production, thereby promoting LDL transcytosis and atherosclerosis progression.Conclusion CAVIN-2 was positively correlated with DM-PAD and promoted LDL transcytosis through the inhibition of eNOS activation, contributing to atherosclerosis development. This study provided clinical evidence linking CAVIN-2 to diabetic PAD and suggested its potential as a biomarker for disease progression.https://www.tandfonline.com/doi/10.1080/07853890.2025.2457526CAVIN-2peripheral artery diseaseatherosclerosistype 2 diabetesLDL transcytosis
spellingShingle Li Wang
Yi Song
Yan Shu
Baorui Xue
Fangyang Yu
Yao Yin
Ziyun Feng
Xiang Ma
Yulin Yao
Yangze Pan
Si Jin
CAVIN-2 positively correlates with diabetic PAD and promotes LDL transcytosis by inhibiting eNOS activation
Annals of Medicine
CAVIN-2
peripheral artery disease
atherosclerosis
type 2 diabetes
LDL transcytosis
title CAVIN-2 positively correlates with diabetic PAD and promotes LDL transcytosis by inhibiting eNOS activation
title_full CAVIN-2 positively correlates with diabetic PAD and promotes LDL transcytosis by inhibiting eNOS activation
title_fullStr CAVIN-2 positively correlates with diabetic PAD and promotes LDL transcytosis by inhibiting eNOS activation
title_full_unstemmed CAVIN-2 positively correlates with diabetic PAD and promotes LDL transcytosis by inhibiting eNOS activation
title_short CAVIN-2 positively correlates with diabetic PAD and promotes LDL transcytosis by inhibiting eNOS activation
title_sort cavin 2 positively correlates with diabetic pad and promotes ldl transcytosis by inhibiting enos activation
topic CAVIN-2
peripheral artery disease
atherosclerosis
type 2 diabetes
LDL transcytosis
url https://www.tandfonline.com/doi/10.1080/07853890.2025.2457526
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