Slevin M, Badimon L, Grau-Olivares M, Ramis M, Sendra J, Morrison M, Krupinski J
School of Biology, Chemistry and Health Science, Manchester Metropolitan University, Manchester, UK.
Mol Biosyst. 2010 Mar;6(3):444-50. doi: 10.1039/b916175a. Epub 2009 Nov 12.
Activation of vasa vasorum (the microvessels supplying the major arteries) at specific sites in the adventitia initiates their proliferation or 'angiogenesis' concomitant with development of atherosclerotic plaques. Haemorrhagic, leaky blood vessels from unstable plaques proliferate abnormally, are of relatively large calibre but are immature neovessels poorly invested with smooth muscle cells and possess structural weaknesses which may contribute to instability of the plaque by facilitation of inflammatory cell infiltration and haemorrhagic complications. Weak neovascular beds in plaque intima as well as activated adventitial blood vessels are potential targets for molecular imaging and targeted drug therapy, however, the majority of tested, currently available imaging and therapeutic agents have been unsuccessful because of their limited capacity to reach and remain stably within the target tissue or cells in vivo. Nanoparticle technology together with magnetic resonance imaging has allowed the possibility of imaging of neovessels in coronary or carotid plaques, and infusion of nanoparticle suspensions using infusion catheters or implant-based drug delivery represents a novel and potentially much more efficient option for treatment. This review will describe the importance of angiogenesis in mediation of plaque growth and development of plaque instability and go on to investigate the possibility of future design of superparamagnetic/perfluorocarbon-derived nanoparticles for imaging of the vasculature in this disease or which could be directed to the adventitial vasa vasorum or indeed intimal microvessels and which can release active payloads directed against primary key external mitogens and intracellular signalling molecules in endothelial cells responsible for their activation with a view to inhibition of angiogenesis.
外膜特定部位的滋养血管(为主要动脉供血的微血管)激活会引发其增殖或“血管生成”,这与动脉粥样硬化斑块的发展相伴。不稳定斑块中出血性、渗漏的血管异常增殖,管径相对较大,但属于不成熟的新生血管,平滑肌细胞覆盖较少,且存在结构弱点,这可能通过促进炎症细胞浸润和出血并发症而导致斑块不稳定。斑块内膜中的薄弱新生血管床以及激活的外膜血管是分子成像和靶向药物治疗的潜在靶点,然而,由于目前大多数已测试的成像和治疗剂在体内到达并稳定存在于靶组织或细胞中的能力有限,因此均未成功。纳米颗粒技术与磁共振成像相结合,使得对冠状动脉或颈动脉斑块中的新生血管进行成像成为可能,并且使用输液导管输注纳米颗粒悬浮液或基于植入物的药物递送代表了一种新颖且可能更有效的治疗选择。本综述将描述血管生成在介导斑块生长和斑块不稳定发展中的重要性,并进而探讨未来设计超顺磁性/全氟化碳衍生纳米颗粒用于对此疾病中的脉管系统进行成像的可能性,或者该纳米颗粒可被导向外膜滋养血管或内膜微血管,并能释放针对负责激活内皮细胞的主要关键外部促细胞分裂剂和细胞内信号分子的活性载荷,以期抑制血管生成。