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血浆纤维连接蛋白-1与动脉僵硬度中肱踝脉搏波速度的关联

Association Between Plasma Fibulin-1 and Brachial-Ankle Pulse Wave Velocity in Arterial Stiffness.

作者信息

Luo Mandi, Yan Dan, Liang Xiaolu, Huang Yi, Luo Pengcheng, Yang Zhen, Zhang Yucong, Xu Ting, Gao Shangbang, Zhang Le, Zhou Yiwu, Shi Qing, Zhang Cuntai, Ruan Lei

机构信息

Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Sciences and Technology, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Cardiovasc Med. 2022 Jul 7;9:837490. doi: 10.3389/fcvm.2022.837490. eCollection 2022.

Abstract

Arterial stiffness forms the basis of cardiovascular diseases (CVD) and is also an independent predictor of CVD risk. Early detection and intervention of arterial stiffness are important for improving the global burden of CVD. Pulse wave velocity (PWV) is the gold standard for assessing arterial stiffness and the molecular mechanism of arterial stiffness remains to be studied. Extracellular matrix (ECM) remodeling is one of the major mechanisms of arterial stiffness. Partial quantitative changes of ECM proteins can be detected in plasma. Therefore, we examined the hypothesis that a discovery proteomic comparison of plasma proteins between high arterial stiffness (baPWV ≥ 1,400 cm/s) and normal arterial stiffness (baPWV < 1,400 cm/s) populations might identify relevant changed ECM proteins for arterial stiffness. Plasma samples were randomly selected from normal arterial stiffness ( = 6) and high arterial stiffness ( = 6) people. Isobaric tags for relative and absolute quantitation (iTRAQ) based quantitative proteomics technique was performed to find a total of 169 differentially expressed proteins (DEPs). Nine ECM proteins were included in all DEPs and were all up-regulated proteins. Fibulin-1 had the highest statistically fold-change (FC = 3.7, < 0.0001) in the high arterial stiffness population compared with the control group during the nine ECM proteins. The expression of plasma fibulin-1 in normal arterial stiffness ( = 112) and high arterial stiffness ( = 72) populations was confirmed through enzyme-linked immunosorbent assay (ELISA). Similarly, ELISA results showed that plasma concentrations of fibulin-1 in the high arterial stiffness group were higher than those in the normal arterial stiffness group (12.69 ± 0.89 vs. 9.84 ± 0.71 μg/ml, < 0.05). Univariate analysis of fibulin-1 with brachial-ankle pulse wave velocity (baPWV) indicated that fibulin-1 was positively correlated with baPWV in all participants ( = 0.32, < 0.01) and a stronger positive correlation between baPWV and fibulin-1 in high arterial stiffness group ( = 0.64, < 0.0001) was found. Multiple regression analysis of factors affecting baPWV showed that fibulin-1 was also a significant determinant of the increased ba-PWV ( = 0.635, = 0.001). Partial correlation analysis showed that baPWV increased with the growth of plasma fibulin-1( = 0.267, < 0.001). In conclusion, our results demonstrated that fibulin-1 is positively correlated with ba-PWV and an independent risk factor for arterial stiffness.

摘要

动脉僵硬度是心血管疾病(CVD)的基础,也是CVD风险的独立预测指标。早期检测和干预动脉僵硬度对于减轻全球CVD负担至关重要。脉搏波速度(PWV)是评估动脉僵硬度的金标准,而动脉僵硬度的分子机制仍有待研究。细胞外基质(ECM)重塑是动脉僵硬度的主要机制之一。血浆中可检测到ECM蛋白的部分定量变化。因此,我们检验了这样一个假设,即对高动脉僵硬度(臂踝脉搏波速度[baPWV]≥1400 cm/s)和正常动脉僵硬度(baPWV<1400 cm/s)人群的血浆蛋白进行发现性蛋白质组学比较,可能会识别出与动脉僵硬度相关的ECM蛋白变化。从正常动脉僵硬度(n = 6)和高动脉僵硬度(n = 6)人群中随机选取血浆样本。采用基于相对和绝对定量的等压标签(iTRAQ)定量蛋白质组学技术,共发现169种差异表达蛋白(DEPs)。所有DEPs中包含9种ECM蛋白,且均为上调蛋白。在这9种ECM蛋白中,与对照组相比,高动脉僵硬度人群中纤连蛋白-1的统计学倍数变化最高(FC = 3.7,P<0.0001)。通过酶联免疫吸附测定(ELISA)证实了正常动脉僵硬度(n = 112)和高动脉僵硬度(n = 72)人群中血浆纤连蛋白-1的表达。同样,ELISA结果显示,高动脉僵硬度组血浆纤连蛋白-1浓度高于正常动脉僵硬度组(12.69±0.89 vs. 9.84±0.71 μg/ml,P<0.05)。对纤连蛋白-1与臂踝脉搏波速度(baPWV)进行单因素分析表明,在所有参与者中纤连蛋白-1与baPWV呈正相关(r = 0.32,P<0.01),且在高动脉僵硬度组中baPWV与纤连蛋白-1之间的正相关性更强(r = 0.64,P<0.0001)。对影响baPWV的因素进行多元回归分析表明,纤连蛋白-1也是ba-PWV升高的重要决定因素(β = 0.635,P = 0.001)。偏相关分析表明,baPWV随血浆纤连蛋白-1的增加而升高(r = 0.267,P<0.001)。总之,我们的结果表明纤连蛋白-1与ba-PWV呈正相关,是动脉僵硬度的独立危险因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c2a/9302601/14d6bf835d18/fcvm-09-837490-g0001.jpg

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