Department of Biomedical Sciences, Panum Institute (L.G.L., M.J.D.), University of Copenhagen, Denmark.
Department of Cardiology, Rigshospitalet, Capital Region, Copenhagen, Denmark (G.M.H., H.B.).
Arterioscler Thromb Vasc Biol. 2022 Jul;42(7):857-864. doi: 10.1161/ATVBAHA.122.317491. Epub 2022 Apr 21.
Materials extracted from atherosclerotic arteries can disclose data about the molecular pathology of cardiovascular disease, but obtaining such samples is complex and requires invasive surgery. To overcome this barrier, this study investigated whether angioplasty balloons inflated during standard percutaneous coronary interventions retain proteins from treated (dilated) atherosclerotic lesions and whether proteomic analysis of this material could provide data on lesion protein profiles and distinguish between patients with stable and unstable coronary artery disease.
Patients with ST-segment-elevation myocardial infarction and stable angina pectoris were subjected to routine percutaneous coronary interventions. All angioplasty balloons inflated in a coronary artery were collected. Proteins retained on the balloons were extracted and analyzed using shotgun proteomic analysis.
Proteomics identified and quantified 1365 unique proteins captured on percutaneous coronary intervention balloons. Control balloons inflated in the ascending aorta showed minimal nonspecific protein binding, indicating specificity to the luminal region of atherosclerotic lesions of the diseased artery wall. Clustering and principal component analyses showed that ST-segment-elevation myocardial infarction and stable angina pectoris subjects could be separated by variations in protein content and abundance. We identified 206 proteins as differentially abundant between ST-segment-elevation myocardial infarction and stable angina pectoris subjects. Pathway analysis indicated several enriched processes in the ST-segment-elevation myocardial infarction group involved in neutrophil-mediated immunity and platelet activation.
Disease-related proteins from coronary artery lesions adhere to angioplasty balloons and constitute a source of material for proteomic analysis. This approach can identify proteins and processes occurring in unstable coronary atherosclerotic lesions and suggest novel therapeutic approaches.
从动脉粥样硬化血管中提取的物质可以揭示心血管疾病的分子病理学数据，但获取这些样本很复杂，需要进行侵入性手术。为了克服这一障碍，本研究调查了在标准经皮冠状动脉介入治疗中充气的血管成形球囊是否保留了经过治疗（扩张）的动脉粥样硬化病变的蛋白质，以及对这种物质的蛋白质组学分析是否可以提供关于病变蛋白谱的数据，并区分稳定型和不稳定型冠心病患者。
患有 ST 段抬高型心肌梗死和稳定型心绞痛的患者接受了常规经皮冠状动脉介入治疗。所有在冠状动脉中充气的血管成形球囊均被收集。使用鸟枪法蛋白质组学分析提取并分析保留在球囊上的蛋白质。
蛋白质组学鉴定和定量了在经皮冠状动脉介入球囊上捕获的 1365 种独特蛋白质。在升主动脉中充气的对照球囊显示出最小的非特异性蛋白质结合，表明其对病变动脉壁动脉粥样硬化病变的管腔区域具有特异性。聚类和主成分分析表明，ST 段抬高型心肌梗死和稳定型心绞痛患者可以通过蛋白质含量和丰度的变化来区分。我们确定了 206 种在 ST 段抬高型心肌梗死和稳定型心绞痛患者之间差异丰富的蛋白质。通路分析表明，ST 段抬高型心肌梗死组中涉及中性粒细胞介导的免疫和血小板激活的几个富集过程。
来自冠状动脉病变的与疾病相关的蛋白质附着在血管成形球囊上，构成蛋白质组学分析的物质来源。这种方法可以识别不稳定型冠状动脉粥样硬化病变中发生的蛋白质和过程，并提出新的治疗方法。
