LOX-1 receptor: A potential link in atherosclerosis and cancer

血管生成 癌变 癌症研究 细胞生物学 癌症 癌细胞 受体 下调和上调 炎症 信号转导 化学 生物 免疫学 生物化学 基因 遗传学
作者
Silvana Balzan,Valter Lubrano
出处
期刊:Life Sciences [Elsevier]
卷期号:198: 79-86 被引量:112
标识
DOI:10.1016/j.lfs.2018.02.024
摘要

Altered production of reactive oxygen species (ROS), causing lipid peroxidation and DNA damage, contributes to the progression of atherosclerosis and cancer. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a lectin-like receptor for oxidized low-density lipoproteins (ox-LDL) primarily expressed in endothelial cells and vasculature-rich organs. LOX-1 receptors is a marker for atherosclerosis, and once activated by ox-LDL or other ligands, stimulates the expression of adhesion molecules, pro-inflammatory signaling pathways and proangiogenic proteins, including NF-kB and VEGF, in vascular endothelial cells and macrophages. Several different types of cancer reported LOX-1 gene upregulation, and numerous interplays exist concerning LOX-1 in atherosclerosis, metabolic diseases and cancer. One of them involves NF-kB, an oncogenic protein that regulates the transcription of several inflammatory genes response. In a model of cellular transformation, the MCF10A ER-Src, inhibition of LOX-1 gene reduces NF-kB activation and the inflammatory and hypoxia pathways, suggesting a mechanistic connection between cellular transformation and atherosclerosis. The remodeling proteins MMP-2 and MMP-9 have been found increased in angiogenesis in atherosclerotic plaque and also in human prostate cancer cells. In this review, we outlined the role of LOX-1 in atherogenesis and tumorigenesis as a potential link in these diseases, suggesting that LOX-1 inhibition could represent a promising strategy in the treatment of atherosclerosis and tumors.
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