Department of Medicine, University of California, Los Angeles, CA, USA.
Circ Res. 2011 Jun 10;108(12):1482-93. doi: 10.1161/CIRCRESAHA.110.234245.
This review focuses on the roles of oxylipids and receptor activator of nuclear factor-κB ligand signaling in calcific cardiovascular disease. Both intimal and valvular calcifications 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, ie, 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 antiosteoclastogenic factors, including the soluble decoy receptor for receptor activator of nuclear factor-κB ligand, 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.
这篇综述重点介绍了氧化脂质和核因子-κB 配体受体激活剂信号在心血管钙化疾病中的作用。内膜和瓣膜钙化都与动脉粥样硬化密切相关，这促使研究人员研究动脉粥样硬化性氧化修饰脂质（氧化脂质）的作用。研究结果已经确定了氧化脂质在诱导血管细胞成骨分化和钙化过程中的分子信号通路。一个令人惊讶的伴随发现是，在真正来自骨骼的成骨细胞中，氧化脂质具有相反的作用，即抑制成骨细胞成熟。这就是骨质疏松症脂质假说的基础。氧化脂质还会在骨环境中诱导破骨细胞吸收，这就提出了一个问题，即在血管环境中是否可以利用破骨细胞进行基于细胞的治疗来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生成因子，包括核因子-κB 配体受体的可溶性诱饵受体，这可能解释了破骨细胞的缺乏和动脉粥样硬化斑块中矿物质的优势。这些因子可能在利用破骨细胞从动脉中去除矿物质沉积方面具有治疗用途。
