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PLoS ONE:减少衰老过程中血管损伤的保护性蛋白

  1. CaP晶体
  2. 血管损伤

来源:生物谷 2014-05-23 15:56

近日,研究人员发现在我们血液中的蛋白如何能减少年龄增长以及诸如动脉粥样硬化、关节炎等疾病对血管的损伤。钙化是心脏发作和中风的主要危险因素。因为磷酸钙(CaP)晶体,血管硬化。CaP晶体在骨骼和牙齿中通常发现

2014年5月22日讯 /生物谷BIOON/--近日,研究人员发现在我们血液中的蛋白如何能减少年龄增长以及诸如动脉粥样硬化、关节炎等疾病对血管的损伤。

钙化是心脏发作和中风的主要危险因素。因为磷酸钙(CaP)晶体的存在,可导致血管硬化。CaP晶体在骨骼和牙齿中通常发现,因为我们老化或疾病的缘故,其在软组织中积累,这可能会导致动脉粥样硬化患者出现并发症。

然而,Babraham研究所一个科学家小组发现CaP如何损伤血管,以及在我们正常血液循环中的蛋白质如何可以帮助防止这个过程。在由British Heart Foundation资助的研究中,研究人员发现CaP晶体被血管细胞所“消耗”,导致细胞内异常高浓度的钙离子,而这被证明是有毒的。

他们发现,血液中两种蛋白:胎球蛋白-A和白蛋白,可以减缓血管细胞CaP晶体的吸收,降低钙离子的释放和防止血管损伤。医生Diane Proudfoot解释说:细胞内钙含量微小变化控制正常细胞功能的许多方面的。当钙含量变得过大,细胞就会死亡。通过延迟这些晶体的吸收,减少钙离子的释放,蛋白胎球蛋白-A和白蛋白可以帮助保持钙离子在一个安全的水平。

这项研究发表在杂志PLOS ONE上,有助开发预防和减少CaP晶体破坏作用的新手段。Proudfoot博士补充说:有趣的是,这些蛋白质水平在慢性肾脏病患者中观察到较低,慢性肾脏病患者由于心血管疾病会承受更高的死亡率。在未来,有可能用人造或从血液中提取的胎球蛋白-A,作为治疗这种蛋白质水平低患者的药物。(生物谷Bioon.com)

Fetuin-A and albumin alter cytotoxic effects of calcium phosphate nanoparticles on human vascular smooth muscle cells

Dautova Y, Kozlova D, Skepper JN, Epple M, Bootman MD, Proudfoot D

Calcification is a detrimental process in vascular ageing and in diseases such as atherosclerosis and arthritis. In particular, small calcium phosphate (CaP) crystal deposits are associated with inflammation and atherosclerotic plaque de-stabilisation. We previously reported that CaP particles caused human vascular smooth muscle cell (VSMC) death and that serum reduced the toxic effects of the particles. Here, we found that the serum proteins fetuin-A and albumin (≥1 μM) reduced intracellular Ca2+ elevations and cell death in VSMCs in response to CaP particles. In addition, CaP particles functionalised with fetuin-A, but not albumin, were less toxic than naked CaP particles. Electron microscopic studies revealed that CaP particles were internalised in different ways; via macropinocytosis, membrane invagination or plasma membrane damage, which occurred within 10 minutes of exposure to particles. However, cell death did not occur until approximately 30 minutes, suggesting that plasma membrane repair and survival mechanisms were activated. In the presence of fetuin-A, CaP particle-induced damage was inhibited and CaP/plasma membrane interactions and particle uptake were delayed. Fetuin-A also reduced dissolution of CaP particles under acidic conditions, which may contribute to its cytoprotective effects after CaP particle exposure to VSMCs. These studies are particularly relevant to the calcification observed in blood vessels in patients with kidney disease, where circulating levels of fetuin-A and albumin are low, and in pathological situations where CaP crystal formation outweighs calcification-inhibitory mechanisms.

 

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