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PCSK9 抑制剂对动脉粥样硬化斑块稳定性的影响:生化和诊断影像学方法的评估。

The Effect of PCSK9 Inhibition on the Stabilization of Atherosclerotic Plaque Determined by Biochemical and Diagnostic Imaging Methods.

机构信息

Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland.

SCANiX Medical Imaging, Ceglana 35, 40-514 Katowice, Poland.

出版信息

Molecules. 2023 Aug 7;28(15):5928. doi: 10.3390/molecules28155928.

Abstract

Atherosclerosis is a multifactorial, progressive, chronic inflammatory disease. Ultrasound and magnetic resonance imaging are the most accurate predictors of atherosclerotic plaque instability (MRI). Cytokines such as osteopontin, osteoprotegerin, and metalloproteinase 9 could be used as the most recent markers to identify and track the efficacy of anti-atherosclerotic therapy. Patients with USG and MRI-verified unstable atherosclerotic plaque were included in the study. Biomarker concentrations were measured and compared before and after PCSK9 inhibitor therapy. Additionally, concentrations prior to treatment were correlated with MRI images of the carotid artery. After treatment with alirocumab, the concentrations of MMP-9 ( < 0.01) and OPN, OPG ( < 0.05) decreased significantly. Furthermore, the results of OPN, OPG, and MMP 9 varied significantly depending on the type of atherosclerotic plaque in the MRI assay. In stable atherosclerotic plaques, the concentrations of OPN and OPG were greater ( < 0.01), whereas the concentration of MMP9 correlated with the instability of the plaque ( < 0.05). We demonstrated, probably for the first time, that alirocumab therapy significantly decreased the serum concentration of atherosclerotic plaque markers. In addition, we demonstrated the relationship between the type of atherosclerotic plaque as determined by carotid MRI and the concentration of these markers.

摘要

动脉粥样硬化是一种多因素、进行性、慢性炎症性疾病。超声和磁共振成像(MRI)是预测动脉粥样硬化斑块不稳定的最准确指标。骨桥蛋白、骨保护素和基质金属蛋白酶 9 等细胞因子可作为最新的标志物,用于识别和跟踪抗动脉粥样硬化治疗的效果。本研究纳入了经超声和 MRI 证实的不稳定动脉粥样硬化斑块患者。测量并比较了患者接受 PCSK9 抑制剂治疗前后的生物标志物浓度。此外,还将治疗前的浓度与颈动脉 MRI 图像进行了相关性分析。在接受阿利西尤单抗治疗后,MMP-9(<0.01)和 OPN、OPG(<0.05)的浓度显著降低。此外,OPN、OPG 和 MMP9 的结果根据 MRI 检测到的动脉粥样硬化斑块类型而显著不同。在稳定的动脉粥样硬化斑块中,OPN 和 OPG 的浓度更高(<0.01),而 MMP9 的浓度与斑块的不稳定性相关(<0.05)。我们首次证明,阿利西尤单抗治疗可显著降低血清中动脉粥样硬化斑块标志物的浓度。此外,我们还证明了颈动脉 MRI 确定的动脉粥样硬化斑块类型与这些标志物浓度之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7583/10421011/611cd7298ff3/molecules-28-05928-g001.jpg

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