Wang Li, Song Yi, Shu Yan, Xue Baorui, Yu Fangyang, Yin Yao, Feng Ziyun, Ma Xiang, Yao Yulin, Pan Yangze, Jin Si
Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Endocrinology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Ann Med. 2025 Dec;57(1):2457526. doi: 10.1080/07853890.2025.2457526. Epub 2025 Jan 31.
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.
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.
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. , 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.
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.
小窝与动脉粥样硬化的发生和发展密切相关。小窝内小窝蛋白-1（CAV1）在动脉粥样硬化发展中的关键作用一直得到支持。然而，其他小窝蛋白对动脉粥样硬化的潜在贡献仍需进一步探索。因此，本研究旨在提供将CAVIN-2与糖尿病外周动脉疾病（PAD）相关联的临床证据及其在低密度脂蛋白（LDL）转胞吞作用中的作用。
共收集115名参与者的血样，包括36名无糖尿病患者（ND）、26名2型糖尿病（T2DM）患者和53名T2DM合并PAD患者（DM-PAD）。采用酶联免疫吸附测定法（ELISA）检测血浆中CAV1、CAVIN-1和CAVIN-2的水平。使用Spearman相关性分析检查CAV1、CAVIN-1、CAVIN-2与糖尿病性PAD之间的相关性。通过受试者工作特征（ROC）曲线分析CAV1和CAVIN-2的预测作用。采用细胞实验研究CAVIN-2对LDL转胞吞作用的影响及其机制。
在T2DM组和DM-PAD组中观察到CAV1和CAVIN-2水平升高，与DM-PAD和PAD严重程度呈正相关。CAV1和CAVIN-2均为DM-PAD的预测指标。此外，敲低CAVIN-2可降低LDL转胞吞作用，而过表达CAVIN-2则可增加LDL转胞吞作用。此外，发现CAVIN-2可抑制内皮型一氧化氮合酶（eNOS）激活和一氧化氮（NO）生成，从而促进LDL转胞吞作用和动脉粥样硬化进展。
CAVIN-2与DM-PAD呈正相关，并通过抑制eNOS激活促进LDL转胞吞作用，从而促进动脉粥样硬化发展。本研究提供了将CAVIN-2与糖尿病性PAD相关联的临床证据，并提示其作为疾病进展生物标志物的潜力。
