Detection of hydroxyapatite in calcified cardiovascular tissues.

Detection of hydroxyapatite in calcified cardiovascular tissues.
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DOI:
10.1016/j.atherosclerosis.2012.07.023
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发表时间:
2012-10
期刊:
影响因子:
5.3
通讯作者:
Tung, Ching-Hsuan
Tung, Ching-Hsuan
中科院分区:
医学2区
文献类型:
--
作者:
Lee, Jae Sam;Morrisett, Joel D.;Tung, Ching-Hsuan

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本研究的目的是建立一种在体外和体外钙化心血管组织中选择性检测人主动脉平滑肌细胞中钙化(羟基磷灰石)成分的方法。该方法使用一种新型光学分子成像对比染料Cy-HABP-19来靶向钙化细胞和组织。一种模拟骨钙素结合亲和力的肽被用于在体外和离体标记羟基磷灰石。在体外刺激、成骨因子和磁悬浮细胞培养诱导的矿化过程早期,对血管平滑肌细胞的形态学变化进行了评价。在成骨因子和磁悬浮环境下,在这些细胞的单层中检测到羟基磷灰石成分。动脉粥样硬化斑块包含多种成分,包括脂质、纤维化、血栓和钙化物质。利用光学成像和Cy-HABP-19分子成像探针,我们证明羟基磷灰石成分可以选择性地与体外人主动脉平滑肌细胞和钙化心血管组织、颈动脉内膜切除术样本和主动脉瓣中的各种钙盐区分。我们的Cy-HABP-19探针在钙化过程的早期阶段选择性地检测了心血管组织中的羟基磷灰石沉积物。这种新的探针使得在细胞和分子水平上研究与血管羟基磷灰石沉积有关的最早事件成为可能。这种靶向选择性分子成像探针方法在揭示早期病理生理变化,导致心血管疾病的进展、消退或稳定方面具有很高的潜力。
The objective of this study is to develop a method for selective detection of the calcific (hydroxyapatite) component in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues ex vivo. This method uses a novel optical molecular imaging contrast dye, Cy-HABP-19, to target calcified cells and tissues. A peptide that mimics the binding affinity of osteocalcin was used to label hydroxyapatite in vitro and ex vivo. Morphological changes in vascular smooth muscle cells were evaluated at an early stage of the mineralization process induced by extrinsic stimuli, osteogenic factors and a magnetic suspension cell culture. Hydroxyapatite components were detected in monolayers of these cells in the presence of osteogenic factors and a magnetic suspension environment. Atherosclerotic plaque contains multiple components including lipidic, fibrotic, thrombotic, and calcific materials. Using optical imaging and the Cy-HABP-19 molecular imaging probe, we demonstrated that hydroxyapatite components could be selectively distinguished from various calcium salts in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues, carotid endarterectomy samples and aortic valves, ex vivo. Hydroxyapatite deposits in cardiovascular tissues were selectively detected in the early stage of the calcification process using our Cy-HABP-19 probe. This new probe makes it possible to study the earliest events associated with vascular hydroxyapatite deposition at the cellular and molecular levels. This target-selective molecular imaging probe approach holds high potential for revealing early pathophysiological changes, leading to progression, regression, or stabilization of cardiovascular diseases.
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