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重症酒精性肝硬化患者的血清抑制人冠状动脉平滑肌细胞的增殖和迁移。

Serum from Patients with Severe Alcoholic Liver Cirrhosis Inhibits Proliferation and Migration of Human Coronary Artery Smooth Muscle Cells.

作者信息

Mechelinck Mare, Peschel Miriam, Habigt Moriz A, Kroy Daniela, Lehrke Michael, Helmedag Marius J, Rossaint Rolf, Barton Matthias, Hein Marc

机构信息

Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany.

Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany.

出版信息

J Clin Med. 2021 Nov 23;10(23):5471. doi: 10.3390/jcm10235471.

Abstract

Liver cirrhosis has been associated with an increased risk of coronary artery disease and clinical complications following percutaneous coronary revascularization. The present study is based on the hypothesis that cirrhosis may influence intimal hyperplasia following PCI. Sera from 10 patients with alcoholic liver cirrhosis and 10 age-matched healthy controls were used to stimulate cultured human coronary artery smooth muscle cells (HCASMC) for 48 h. HCASMC proliferation, migration, gene expression and apoptosis were investigated. Serum concentrations of growth factors and markers of liver function were also determined in patients and healthy controls. Treatment of HCASMC with patient sera reduced cell proliferation and migration ( < 0.05 vs. healthy controls), whereas apoptosis was unaffected ( = 0.160). Expression of genes associated with a synthetic vascular smooth muscle cell phenotype was decreased in cells stimulated with serum from cirrhotic patients (RBP1, = 0.001; SPP1, = 0.003; KLF4, = 0.004). Platelet-derived growth factor-BB serum concentrations were lower in patients ( = 0.001 vs. controls). The results suggest the presence of circulating factors in patients with alcoholic liver cirrhosis affecting coronary smooth muscle cell growth. These findings may have implications for clinical outcomes following percutaneous coronary revascularization in these patients.

摘要

肝硬化与冠状动脉疾病风险增加以及经皮冠状动脉血运重建术后的临床并发症相关。本研究基于肝硬化可能影响经皮冠状动脉介入治疗(PCI)后内膜增生的假设。使用10例酒精性肝硬化患者和10例年龄匹配的健康对照者的血清刺激培养的人冠状动脉平滑肌细胞(HCASMC)48小时。研究了HCASMC的增殖、迁移、基因表达和凋亡情况。还测定了患者和健康对照者血清中生长因子浓度和肝功能标志物。用患者血清处理HCASMC可降低细胞增殖和迁移(与健康对照相比,<0.05),而凋亡未受影响(=0.160)。用肝硬化患者血清刺激的细胞中,与合成型血管平滑肌细胞表型相关的基因表达降低(RBP1,=0.001;SPP1,=0.003;KLF4,=0.004)。患者血小板衍生生长因子-BB血清浓度较低(与对照相比,=0.001)。结果表明酒精性肝硬化患者体内存在影响冠状动脉平滑肌细胞生长的循环因子。这些发现可能对这些患者经皮冠状动脉血运重建术后的临床结局有影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/433b/8658341/5070849b11b8/jcm-10-05471-g001.jpg

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