Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification.
Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification.
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DOI：
10.1038/nmat3627
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发表时间：
2013-06
期刊：
影响因子：
41.2
通讯作者：
Stevens MM
中科院分区：
文献类型：
--
作者：
Bertazzo S;Gentleman E;Cloyd KL;Chester AH;Yacoub MH;Stevens MM
钙化物质在心血管组织中的积累被认为涉及细胞化学、细胞外基质和系统信号，然而，其精确组成和纳米级结构在很大程度上仍未被探索。使用纳米分析电子显微镜技术，我们检查了患有和不患有钙化性心血管疾病的患者的瓣膜、主动脉和冠状动脉，并检测了球形磷酸钙颗粒，无论是否存在钙化病变。而被钙化病变标记为骨特异性蛋白骨钙素的组织，仅存在颗粒的组织仅表达早期成骨细胞转录因子，这表明球形颗粒的定位可能先于成熟成骨细胞和钙化病变的出现。我们也用聚焦离子束检查了切片后的病变，发现球形颗粒由高度结晶的羟基磷灰石组成，其晶体学和结构与骨矿物不同。综上所述，这些数据表明矿化球形颗粒可能在钙化病变的形成中起着重要作用。它们在各种心血管组织和各种疾病患者中普遍存在，进一步表明病变的形成可能遵循一个共同的过程。事实上，将材料科学技术应用于异位和正位钙化具有很大的潜力，可以为钙化性心血管疾病的病理生理过程提供重要的见解。
The accumulation of calcified material in cardiovascular tissue is thought to involve cytochemical, extracellular matrix and systemic signals, however, its precise composition and nano-scale architecture remain largely unexplored. Using nano-analytical electron microscopy techniques, we examined valves, aortas, and coronary arteries from patients with and without calcific cardiovascular disease and detected spherical calcium phosphate particles, regardless of the presence of calcific lesions. While tissue marked by calcific lesions immunogold labelled for the bone-specific protein osteocalcin, tissue on which particles alone were present only expressed early osteoblastic transcription factors, suggesting that the localization of spherical particles may precede the appearance of mature osteoblasts and calcific lesions. We also examined lesions after sectioning with a focused ion beam and found that spherical particles are composed of highly crystalline hydroxyapatite which crystallographically and structurally differed from bone mineral. Taken together, these data suggest that mineralized spherical particles may play a fundamental role in calcific lesion formation. Their ubiquitous presence in varied cardiovascular tissues and from patients with a spectrum of diseases, further suggests that lesion formation may follow a common process. Indeed, applying materials science techniques to ectopic and orthotopic calcification has great potential to lend critical insights into pathophysiological processes underlying calcific cardiovascular disease.
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DOI：
10.1073/pnas.1208916109
发表时间：
2012-08-28
影响因子：
11.1
作者：
Boonrungsiman, Suwimon;Gentleman, Eileen;Stevens, Molly M.
通讯作者：
Stevens, Molly M.
DOI：
10.1016/0735-1097(93)90249-z
发表时间：
1993-04-01
影响因子：
24
作者：
LINDROOS, M;KUPARI, M;TILVIS, R
通讯作者：
TILVIS, R
DOI：
10.1073/pnas.0914218107
发表时间：
2010-04-06
影响因子：
11.1
作者：
Mahamid, Julia;Aichmayer, Barbara;Addadi, Lia
通讯作者：
Addadi, Lia
影响因子：
4.6
作者：
Langanay, Thierry;Flecher, Erwan;Leguerrier, Alain
通讯作者：
Leguerrier, Alain
影响因子：
3.7
作者：
McNally EA;Schwarcz HP;Botton GA;Arsenault AL
通讯作者：
Arsenault AL