Gargiulo Sara, Gramanzini Matteo, Mancini Marcello
Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145 Naples, Italy.
Int J Mol Sci. 2016 Sep 9;17(9):1511. doi: 10.3390/ijms17091511.
Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE(-/-) and ApoE(-/-)Fbn1C1039G(+/-) mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies.
动脉粥样硬化的特征是动脉血管内膜斑块,其发展缓慢,在某些情况下可能会自发破裂,随后引发心脏病发作或中风。目前,非侵入性诊断工具不足以筛查具有急性并发症高风险的动脉粥样硬化病变。因此,科学界的注意力集中在使用分子成像来识别易损斑块上。基因工程小鼠模型,如载脂蛋白E(ApoE)基因敲除(ApoE(-/-))和ApoE(-/-)Fbn1C1039G(+/-)小鼠,已被证明可用于测试针对相关分子过程生物标志物的新型探针,以表征易损斑块,如血管内皮生长因子受体(VEGFR)-1、VEGFR-2、细胞间黏附分子(ICAM)-1、P-选择素和整合素,以及用于开发潜在的转化工具,以识别可能从早期治疗干预中受益的高危患者。本综述总结了易损斑块的主要动物模型,重点是基因改造小鼠,以及最新的临床前分子成像策略。