Porto Annalisa, Palumbo Roberta, Pieroni Maurizio, Aprigliano Gianfranco, Chiesa Roberto, Sanvito Francesca, Maseri Attilio, Bianchi Marco E
San Raffaele Scientific Institute, Milan, Italy.
FASEB J. 2006 Dec;20(14):2565-6. doi: 10.1096/fj.06-5867fje. Epub 2006 Oct 23.
High mobility group box 1 protein (HMGB1) is a chromatin component leaked out by necrotic cells and actively secreted by activated myeloid cells. The extracellular protein is a potent mediator of tissue remodeling. We show here that human atherosclerotic plaques, but not normal arteries, produce extracellular HMGB1. Secreted HMGB1 originates from endothelial cells, by neointimal foam cells, and also smooth muscle cells (SMCs). SMCs are an unexpected source for secreted HMGB1, since they normally express much lower amounts of HMGB1 than other cells types, and they do not secrete it. However, cultured SMCs actively secrete HMGB1 after cholesterol loading. In turn, in response to HMGB1, SMCs proliferate, migrate, and secrete more HMGB1. Thus, SMCs are both a source and a target of HMGB1; blocking HMGB1 secretion by SMCs can be an important strategy for treatment of atherosclerotic disease and in particular restenosis.
高迁移率族蛋白B1（HMGB1）是一种由坏死细胞释放并由活化的髓样细胞主动分泌的染色质成分。这种细胞外蛋白是组织重塑的强效介质。我们在此表明，人类动脉粥样硬化斑块而非正常动脉会产生细胞外HMGB1。分泌的HMGB1源自内皮细胞、新生内膜泡沫细胞以及平滑肌细胞（SMC）。SMC是分泌型HMGB1的一个意外来源，因为它们通常表达的HMGB1量比其他细胞类型低得多，且它们并不分泌HMGB1。然而，胆固醇加载后，培养的SMC会主动分泌HMGB1。反过来，作为对HMGB1的响应，SMC会增殖、迁移并分泌更多的HMGB1。因此，SMC既是HMGB1的来源也是其靶点；阻断SMC分泌HMGB1可能是治疗动脉粥样硬化疾病尤其是再狭窄的重要策略。
