Department of Chemistry , University of California , Berkeley , California 94720 , United States.
Materials Sciences Division , Lawrence Berkeley National Laboratories , Berkeley , California 94720 , United States.
Bioconjug Chem. 2018 Aug 15;29(8):2526-2530. doi: 10.1021/acs.bioconjchem.8b00453. Epub 2018 Aug 2.
Atherosclerosis is a cardiovascular disease characterized by the formation of lipid-rich plaques within the walls of large arteries. Over time, a portion of these lesions can detach and lead to serious complications, such as strokes or heart attacks. Currently, there is no clinically effective way to detect the presence of atherosclerosis in patients until it has reached a relatively advanced stage. Furthermore, increasing evidence suggests that the pathobiological behavior of plaques is determined mainly by their composition, and not their size, which is the parameter usually monitored with current imaging techniques. In this work, we report protein-based agents that target the vascular cell adhesion molecule (VCAM1), a protein that plays a crucial role in atherosclerosis progression. In vivo experiments with murine atherosclerosis models indicated that the targeted protein nanoparticles were successful in detecting plaques of various sizes in the descending aorta and the aortic arch. This finding encourages the further development of these nanoscale agents for applications in the imaging, diagnosis, and treatment of cardiovascular diseases.
动脉粥样硬化是一种心血管疾病，其特征是大血管壁内形成富含脂质的斑块。随着时间的推移，这些病变的一部分可能会脱落，导致严重的并发症，如中风或心脏病发作。目前，在动脉粥样硬化达到相对较高级别之前，临床上尚无有效方法检测其存在。此外，越来越多的证据表明，斑块的病理生物学行为主要取决于其组成，而不是其大小，而这是目前常用的成像技术监测的参数。在这项工作中，我们报告了靶向血管细胞黏附分子（VCAM1）的基于蛋白质的试剂，VCAM1 是在动脉粥样硬化进展中起关键作用的一种蛋白质。用鼠动脉粥样硬化模型进行的体内实验表明，靶向蛋白纳米颗粒成功地检测到降主动脉和主动脉弓中各种大小的斑块。这一发现鼓励进一步开发这些纳米级试剂，用于心血管疾病的成像、诊断和治疗。
