Breland Unni M, Halvorsen Bente, Hol Johanna, Øie Erik, Paulsson-Berne Gabrielle, Yndestad Arne, Smith Camilla, Otterdal Kari, Hedin Ulf, Waehre Torgun, Sandberg Wiggo J, Frøland Stig S, Haraldsen Guttorm, Gullestad Lars, Damås Jan K, Hansson Gøran K, Aukrust Pål
Research Institute for Internal Medicine, Rikshospitalet, University of Oslo, Norway.
Arterioscler Thromb Vasc Biol. 2008 May;28(5):1005-11. doi: 10.1161/ATVBAHA.108.162305. Epub 2008 Feb 14.
We examined the role of the CXCR2 ligand growth-related oncogene (GRO) alpha in human atherosclerosis.
GROalpha levels were examined by enzyme immunoassay, real-time quantitative RT-PCR, and cDNA microarrays. The in vitro effect of statins on GROalpha was examined in endothelial cells and THP-1 macrophages. Our main findings were: (1) GROalpha was among the 10 most differentially expressed transcripts comparing peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD) and healthy controls. (2) Both patients with stable (n=41) and particularly those with unstable (n=47) angina had increased plasma levels of GROalpha comparing controls (n=20). (3) We found increased expression of GROalpha within symptomatic carotid plaques, located to macrophages and endothelial cells. (4) GROalpha enhanced the release of matrix metalloproteinases in vascular smooth muscle cells, and increased the binding of acetylated LDL in macrophages. (5) Atorvastatin downregulated GROalpha levels as shown both in vitro in endothelial cells and macrophages and in vivo in PBMCs from CAD patients. (6) The effect on GROalpha in endothelial cells involved increased storage and reduced secretion of GROalpha.
GROalpha could be involved in atherogenesis and plaque destabilization, potentially contributing to inflammation, matrix degradation, and lipid accumulation within the atherosclerotic lesion.
我们研究了CXCR2配体生长相关癌基因（GRO）α在人类动脉粥样硬化中的作用。
通过酶免疫测定、实时定量逆转录聚合酶链反应（RT-PCR）和cDNA微阵列检测GROα水平。在血管内皮细胞和THP-1巨噬细胞中检测他汀类药物对GROα的体外作用。我们的主要发现如下：（1）在比较冠心病（CAD）患者和健康对照者外周血单个核细胞（PBMC）时，GROα是差异表达最明显的10种转录本之一。（2）稳定型心绞痛患者（n = 41），尤其是不稳定型心绞痛患者（n = 47），与对照组（n = 20）相比，血浆GROα水平升高。（3）我们发现有症状的颈动脉斑块内GROα表达增加，且定位于巨噬细胞和血管内皮细胞。（4）GROα可增强血管平滑肌细胞中基质金属蛋白酶的释放，并增加巨噬细胞中乙酰化低密度脂蛋白的结合。（5）阿托伐他汀可下调GROα水平，这在体外血管内皮细胞和巨噬细胞以及CAD患者PBMC的体内实验中均得到证实。（6）阿托伐他汀对血管内皮细胞中GROα的作用包括增加其储存和减少其分泌。
GROα可能参与动脉粥样硬化的发生和斑块不稳定，可能导致动脉粥样硬化病变内的炎症、基质降解和脂质蓄积。
