School of Pharmacy , University of Wisconsin-Madison , Madison , Wisconsin 53705 , United States.
Davis Heart and Lung Research Institute , The Ohio State University , Columbus , Ohio 43210 , United States.
J Proteome Res. 2019 Apr 5;18(4):1669-1678. doi: 10.1021/acs.jproteome.8b00941. Epub 2019 Mar 11.
Restenosis, or renarrowing of the arterial lumen, is a common recurrent disease following balloon angioplasty and stenting treatments for cardiovascular disease. A major technical barrier for deciphering restenotic mechanisms is the dynamic, spatial profiling of bioactive lipids in the arterial wall, especially in small animals. Here, applying matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI), we conducted the first lipidomic study of temporal-spatial profiling in a small animal model of angioplasty-induced restenosis. Cross sections were collected 3, 7, and 14 days after balloon angioplasty of rat carotid arteries. MALDI-MSI analyses showed that diacylglycerols (DAGs), signaling lipids associated with restenosis, and lysophosphatidylcholines (LysoPCs), whose function was uncharacterized in restenosis, dramatically increased at postangioplasty day 7 and day 14 in the neointimal layer of balloon-injured arteries compared to uninjured controls. In contrast, sphingomyelins (SMs) did not increase, but rather decreased at day 3, day 7, and day 14 in injured arteries versus the uninjured control arteries. These results revealed previously unexplored distinct temporal-spatial lipid dynamics in the restenotic arterial wall. Additionally, we employed time-of-flight secondary ion mass spectrometry (TOF-SIMS) tandem MS imaging for both molecular identification and imaging at high spatial resolution. These imaging modalities provide powerful tools for unraveling novel mechanisms of restenosis involving lipids or small signaling molecules.
再狭窄，即动脉管腔的再狭窄，是心血管疾病经球囊血管成形术和支架置入治疗后的一种常见复发疾病。解析再狭窄机制的一个主要技术障碍是在动脉壁中动态、空间解析生物活性脂质，尤其是在小动物中。在这里，我们应用基质辅助激光解吸/电离质谱成像（MALDI-MSI），首次对血管成形术后再狭窄的小动物模型进行了时空脂质组学研究。在大鼠颈动脉球囊血管成形术后 3、7 和 14 天收集横截面。MALDI-MSI 分析表明，二酰基甘油（DAGs），与再狭窄相关的信号脂质，以及溶血磷脂酰胆碱（LysoPCs），其在再狭窄中的功能尚未确定，在损伤动脉的新生内膜层中，与未损伤对照组相比，在血管成形术后第 7 天和第 14 天显著增加。相比之下，鞘磷脂（SMs）在损伤动脉中并未增加，而是在第 3 天、第 7 天和第 14 天下降。这些结果揭示了再狭窄动脉壁中以前未探索到的独特时空脂质动力学。此外，我们还采用飞行时间二次离子质谱（TOF-SIMS）串联 MS 成像来进行分子鉴定和高空间分辨率成像。这些成像方式为揭示涉及脂质或小信号分子的再狭窄新机制提供了有力工具。
