Plasmacytoid dendritic cells contribute to vascular endothelial dysfunction in type 2 diabetes.
Plasmacytoid dendritic cells contribute to vascular endothelial dysfunction in type 2 diabetes.
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DOI：
10.3389/fcvm.2023.1222243
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发表时间：
2023
影响因子：
3.6
通讯作者：
Matrougui, K.
中科院分区：
文献类型：
--
作者：
Alluri, K.;Srinivas, B.;Belmadani, S.;Matrougui, K.
2型糖尿病（T2 D）与大血管和微血管功能障碍引起的心血管疾病风险增加相关。本研究旨在探讨浆细胞样树突状细胞（pDC）在T2 D相关血管功能障碍中的潜在参与。从db/db和对照小鼠分离pDC。发现与来自对照小鼠的pDC相比，来自db/db小鼠的pDC响应于ATP而损害内皮细胞eNOS磷酸化，并降低血管内皮依赖性舒张。此外，当用高葡萄糖和脂质刺激过夜时，来自对照小鼠的分离的CD 4+细胞和来自db/db小鼠的分离的pDC显示出升高水平的ER应激、炎症和凋亡标志物。流式细胞术显示db/db小鼠中pDC频率高于对照组。在体内，在雄性和雌性db/db小鼠中使用抗PDCA-1抗体减少pDC 4周显著改善了血管内皮功能和eNOS磷酸化。pDC可能通过损害内皮细胞功能而导致T2 D中的血管功能障碍。用抗PDCA-1抗体靶向pDC可能代表了改善T2 D患者血管内皮功能的有希望的治疗策略。这项研究为T2 D相关血管功能障碍的发病机制提供了新的见解，并强调了免疫调节疗法治疗这种并发症的潜力。进一步的研究是必要的，以探索这种方法的临床潜力。
Type 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. pDCs 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. pDCs 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.
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DOI：
10.4049/jimmunol.1002615
发表时间：
2011-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jagannathan-Bogdan M;McDonnell ME;Shin H;Rehman Q;Hasturk H;Apovian CM;Nikolajczyk BS
通讯作者：
Nikolajczyk BS
DOI：
10.1161/hypertensionaha.112.192500
发表时间：
2012-07
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Galán M;Kassan M;Choi SK;Partyka M;Trebak M;Henrion D;Matrougui K
通讯作者：
Matrougui K
影响因子：
4
作者：
Tian Y;Fopiano KA;Patel VS;Feher A;Bagi Z
通讯作者：
Bagi Z
DOI：
10.2174/1874192401004010240
发表时间：
2010-11-26
期刊：
The open cardiovascular medicine journal
影响因子：
--
作者：
Karasu C
通讯作者：
Karasu C
增强的NF-κB活性通过2型糖尿病中的PARP-1-，SP-1-和COX-2依赖性机制损害了血管功能。
影响因子：
7.7
作者：
Kassan M;Choi SK;Galán M;Bishop A;Umezawa K;Trebak M;Belmadani S;Matrougui K
通讯作者：
Matrougui K