Nanostructural analysis of distinct nucleation sites in pathological mineralization

Nanostructural analysis of distinct nucleation sites in pathological mineralization
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病理矿化中不同成核位点的纳米结构分析

DOI:
10.1039/d1ma00273b
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发表时间:
2021
期刊:
影响因子:
5
通讯作者:
Matsumoto Takuya
Matsumoto Takuya
中科院分区:
--
文献类型:
--
作者:
Hara Emilio Satoshi;Oozawa Susumu;Nagaoka Noriyuki;Okada Masahiro;Kasahara Shingo;Matsumoto Takuya

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病理性矿化,如动脉粥样硬化或生物材料移植后的矿化,与全世界数百万人的死亡有关。对病理性矿化中矿物成核机制的深入了解将促进新型生物激发材料/技术的发展,作为疾病预防或骨组织重建的治疗手段。本研究的目的是从材料科学的角度对动脉粥样硬化矿化成核部位进行系统的超微结构分析。人类动脉粥样硬化组织的组织学染色、超微结构分析和选定区域元素图谱显示,胶原区和脂质区分别有两个不同的成核位点,由磷脂大泡(平均827±470 nm)和非泡状磷脂组成。在这两个地点,最初的矿物被确定为无定形磷酸钙(ACP),然后转化为羟基磷灰石(HAp)。体外矿化试验通过在2 mM CaCl2中培养非囊泡低(LDL)和高(HDL)密度脂蛋白和胆固醇2天进行,不添加磷酸盐。形成的矿物中的钙离子,用原子吸收(AA)光谱测量,表明只有LDL矿化。然后,我们评估了主要磷脂,磷脂酰丝氨酸(PS)和磷脂酰胆碱(PC)在相同条件下的矿化。AA和矿物干重的测定结果表明,PS比PC矿化程度更高,可能是由于其水解速率更高。与体内研究结果相似,PS矿化最初形成ACP,然后结晶成HAp。综上所述,这些结果表明动脉粥样硬化涉及两个不同的成核位点,非泡状磷脂是动脉粥样硬化矿物形成的主要成核位点之一。
Pathological mineralization, such as that in atherosclerosis or following transplantation of biomaterials, is associated with millions of deaths worldwide. A deeper understanding of the mechanisms underlying mineral nucleation in pathological mineralization will facilitate the development of novel bioinspired materials/techniques as therapeutics for either disease prevention or bone tissue reconstruction. The objective of this study was to perform a systematic and ultrastructural analysis of the nucleation sites of atherosclerotic mineralization from the viewpoint of material science. Histological staining, ultrastructural analysis, and selected area elemental mapping of human atherosclerotic tissues revealed two different nucleation sites in a collagenous and a lipidic area, respectively, comprising phospholipidic large vesicles (average 827 ± 470 nm) and non-vesicular phospholipids. In both sites, the initial minerals were identified to be amorphous calcium phosphate (ACP), which then transformed into hydroxyapatite (HAp). Mineralization assays in vitro was performed by incubating non-vesicular low- (LDL) and high- (HDL) density lipoprotein and cholesterol in 2 mM CaCl2 for 2 days, without additional phosphate. Calcium ions in the formed minerals, measured using atomic absorption (AA) spectroscopy, showed that only LDL was mineralized. We then evaluated the mineralization of the major phospholipids, phosphatidylserine (PS) and phosphatidylcholine (PC) under the same conditions. The results of AA and mineral dry weight showed that PS was more abundantly mineralized than PC, most likely due to its higher hydrolysis rate. Similar to the in vivo findings, PS mineralization initially formed ACP, which then crystallized into HAp. Taken together, these results indicated that atherosclerosis involves two distinct nucleation sites and that non-vesicular phospholipids were one of the major nucleation sites for atherosclerotic mineral formation.
DOI: 10.1186/s12944-019-0957-z
发表时间: 2019-01-22
影响因子: 4.5
作者:
Rauschert, Sebastian;Gazquez, Antonio;Koletzko, Berthold
通讯作者: Koletzko, Berthold
DOI: 10.1016/j.atherosclerosis.2017.03.005
发表时间: 2017-04-01
期刊: ATHEROSCLEROSIS
影响因子: 5.3
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DOI: 10.3390/ijms21155327
发表时间: 2020-08-01
影响因子: 5.6
作者:
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通讯作者: Matsumoto, Takuya
DOI: 10.2741/3887
发表时间: 2011-06
期刊: Frontiers in bioscience
影响因子: --
作者:
R. Wuthier;G. Lipscomb
通讯作者: R. Wuthier;G. Lipscomb
DOI: 10.1039/c8tb01544a
发表时间: 2018-10-14
影响因子: 7
作者:
Hara, Emilio Satoshi;Okada, Masahiro;Matsumoto, Takuya
通讯作者: Matsumoto, Takuya