The roles of lipid oxidation products and receptor activator of nuclear factor-κB signaling in atherosclerotic calcification.
The roles of lipid oxidation products and receptor activator of nuclear factor-κB signaling in atherosclerotic calcification.
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DOI：
10.1161/circresaha.110.234245
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发表时间：
2011-06-10
影响因子：
20.1
通讯作者：
Tintut Y
中科院分区：
文献类型：
--
作者：
Demer L;Tintut Y
本文就氧脂和核因子-kappaB受体激活剂配体(RANKL)信号在钙化性心血管疾病中的作用作一综述。动脉内膜和瓣膜钙化都与动脉粥样硬化密切相关，这导致研究人员研究了导致动脉粥样硬化的氧化修饰脂质(Oxlipids)的作用。结果已经确定了氧合脂诱导血管细胞成骨分化和钙化的分子信号。一个令人惊讶的伴随发现是，在真正的骨骼成骨细胞中，氧合脂质具有相反的作用，即抑制成骨细胞的成熟。这是骨质疏松症的脂质假说的基础。氧化脂还可以在骨环境中诱导骨吸收破骨细胞，这提出了一个问题，即是否可以在血管环境中利用吸收破骨细胞进行基于细胞的治疗，以去除动脉壁矿物质沉积。挑战在于，血管细胞产生抗破骨细胞因子，包括RANKL的可溶性诱骗受体，这可能是导致动脉粥样硬化斑块中吸收细胞稀少和矿物质占优势的原因。这些因子可能在破骨细胞去除动脉中的矿物质沉积方面具有治疗作用。
This review focuses on the roles of oxylipids and receptor activator of nuclear factor-kappa B ligand (RANKL) signaling in calcific cardiovascular disease. Both intimal and valvular calcification are closely associated with atherosclerosis, leading investigators to study the role of atherogenic oxidatively modified lipids (oxylipids). Results have identified the molecular signaling through which oxylipids induce osteogenic differentiation and calcification in vascular cells. A surprising concomitant finding was that, in bona fide osteoblasts from skeletal bone, oxylipids have the opposite effect, i.e. inhibiting osteoblastic maturation. This is the basis for the lipid hypothesis of osteoporosis. Oxylipids also induce resorptive osteoclastic cells within the bone environment, raising the question of whether resorptive osteoclasts can be harnessed in the vascular context for cell-based therapy to remove artery wall mineral deposits. The challenge is that, vascular cells produce anti-osteoclastogenic factors, including the soluble decoy receptor for RANKL, possibly accounting for the paucity of resorptive cells and the dominance of mineral in atherosclerotic plaque. These factors may have therapeutic use in osteoclastogenic removal of mineral deposits from arteries.