Plasmacytoid dendritic cells contribute to vascular endothelial dysfunction in type 2 diabetes
ObjectiveType 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease due to macro- and microvascular dysfunction. This study aimed to investigate the potential involvement of plasmacytoid dendritic cells (pDCs) in T2D-related vascular dysfunction.Approach and resultspDCs wer...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1222243/full |
| _version_ | 1797448663437410304 |
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| author | K. Alluri B. Srinivas S. Belmadani K. Matrougui |
| author_facet | K. Alluri B. Srinivas S. Belmadani K. Matrougui |
| author_sort | K. Alluri |
| collection | DOAJ |
| description | ObjectiveType 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease due to macro- and microvascular dysfunction. This study aimed to investigate the potential involvement of plasmacytoid dendritic cells (pDCs) in T2D-related vascular dysfunction.Approach and resultspDCs were isolated from db/db and control mice. It was found that pDCs from db/db mice impaired endothelial cell eNOS phosphorylation in response to ATP and decreased vascular endothelium-dependent relaxation compared to pDCs from control mice. Moreover, isolated CD4+ cells from control mice, when stimulated overnight with high glucose and lipids, and isolated pDCs from db/db mice, display elevated levels of ER stress, inflammation, and apoptosis markers. Flow cytometry revealed that pDC frequency was higher in db/db mice than in controls. In vivo, the reduction of pDCs using anti-PDCA-1 antibodies in male and female db/db mice for 4 weeks significantly improved vascular endothelial function and eNOS phosphorylation.ConclusionpDCs may contribute to vascular dysfunction in T2D by impairing endothelial cell function. Targeting pDCs with anti-PDCA-1 antibodies may represent a promising therapeutic strategy for improving vascular endothelial function in T2D patients. This study provides new insights into the pathogenesis of T2D-related vascular dysfunction and highlights the potential of immunomodulatory therapies for treating this complication. Further studies are warranted to explore the clinical potential of this approach. |
| first_indexed | 2024-03-09T14:13:37Z |
| format | Article |
| id | doaj.art-43e2758007f14d91a7e585d340b990cd |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-03-09T14:13:37Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-43e2758007f14d91a7e585d340b990cd2023-11-29T05:30:42ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-11-011010.3389/fcvm.2023.12222431222243Plasmacytoid dendritic cells contribute to vascular endothelial dysfunction in type 2 diabetesK. AlluriB. SrinivasS. BelmadaniK. MatrouguiObjectiveType 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease due to macro- and microvascular dysfunction. This study aimed to investigate the potential involvement of plasmacytoid dendritic cells (pDCs) in T2D-related vascular dysfunction.Approach and resultspDCs were isolated from db/db and control mice. It was found that pDCs from db/db mice impaired endothelial cell eNOS phosphorylation in response to ATP and decreased vascular endothelium-dependent relaxation compared to pDCs from control mice. Moreover, isolated CD4+ cells from control mice, when stimulated overnight with high glucose and lipids, and isolated pDCs from db/db mice, display elevated levels of ER stress, inflammation, and apoptosis markers. Flow cytometry revealed that pDC frequency was higher in db/db mice than in controls. In vivo, the reduction of pDCs using anti-PDCA-1 antibodies in male and female db/db mice for 4 weeks significantly improved vascular endothelial function and eNOS phosphorylation.ConclusionpDCs may contribute to vascular dysfunction in T2D by impairing endothelial cell function. Targeting pDCs with anti-PDCA-1 antibodies may represent a promising therapeutic strategy for improving vascular endothelial function in T2D patients. This study provides new insights into the pathogenesis of T2D-related vascular dysfunction and highlights the potential of immunomodulatory therapies for treating this complication. Further studies are warranted to explore the clinical potential of this approach.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1222243/fulltype 2 diabetesPlasmacytoid dendritic cells (pDCs)endothelial dysfunctioninflammationsignaling |
| spellingShingle | K. Alluri B. Srinivas S. Belmadani K. Matrougui Plasmacytoid dendritic cells contribute to vascular endothelial dysfunction in type 2 diabetes Frontiers in Cardiovascular Medicine type 2 diabetes Plasmacytoid dendritic cells (pDCs) endothelial dysfunction inflammation signaling |
| title | Plasmacytoid dendritic cells contribute to vascular endothelial dysfunction in type 2 diabetes |
| title_full | Plasmacytoid dendritic cells contribute to vascular endothelial dysfunction in type 2 diabetes |
| title_fullStr | Plasmacytoid dendritic cells contribute to vascular endothelial dysfunction in type 2 diabetes |
| title_full_unstemmed | Plasmacytoid dendritic cells contribute to vascular endothelial dysfunction in type 2 diabetes |
| title_short | Plasmacytoid dendritic cells contribute to vascular endothelial dysfunction in type 2 diabetes |
| title_sort | plasmacytoid dendritic cells contribute to vascular endothelial dysfunction in type 2 diabetes |
| topic | type 2 diabetes Plasmacytoid dendritic cells (pDCs) endothelial dysfunction inflammation signaling |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1222243/full |
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