Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Vascular Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands.
Atherosclerosis. 2017 Nov;266:128-135. doi: 10.1016/j.atherosclerosis.2017.09.025. Epub 2017 Sep 22.
Previously, we showed that patients undergoing carotid endarterectomy have an increased risk for major atherosclerotic events in the presence of moderate or poor kidney function. Acceleration of vascular inflammatory responses is considered to be causally involved in progression of atherogenesis and poor outcome in chronic kidney disease patients. The association between kidney function and plaque composition has not been thoroughly investigated yet. The aim of this study was to investigate the association between kidney function and atherosclerotic plaque composition in patients undergoing carotid endarterectomy.
Atherosclerotic plaques, harvested from 1796 patients who underwent carotid endarterectomy, were immunohistochemically stained for macrophages, smooth muscle cells, calcifications, collagen, microvessels, lipid core size and intraplaque hemorrhage. Cytokines were measured in plaque and plasma and associated with kidney function. Quantitative proteomics were performed on 40 carotid plaques and associated with kidney function.
Decreased kidney function was associated with increased odds ratio of intraplaque hemorrhage, OR 1.15 (95% CI; 1.02-1.29 (p = 0.024)) and increased odds ratio of fibrous-atheromatous plaques (plaques with lipid core presenting more than 10% of total plaque surface) OR 1.21 (95% CI; 1.07-1.38 (p = 0.003)) per decrease of 20 points in eGFR. Proteomics revealed that decreased kidney function was associated with upregulation of the classical pathway of the complement system and the intrinsic pathway of the coagulation system.
Decreased kidney function was associated with plaque hemorrhage but not with inflammatory plaque characteristics. Our data suggests that other pathways than the inflammation-pathway are involved in plaque vulnerability and poor outcome in patients with decreased kidney function.
此前，我们发现肾功能中度或重度受损的颈动脉内膜切除术患者发生主要动脉粥样硬化事件的风险增加。血管炎症反应的加速被认为与动脉粥样硬化的进展以及慢性肾脏病患者的不良预后密切相关。然而，肾功能与斑块成分之间的关系尚未得到充分研究。本研究旨在探讨颈动脉内膜切除术患者肾功能与动脉粥样硬化斑块成分之间的关系。
对 1796 例行颈动脉内膜切除术的患者的动脉粥样硬化斑块进行免疫组织化学染色，以检测巨噬细胞、平滑肌细胞、钙化、胶原、微血管、脂质核心大小和斑块内出血。检测斑块和血浆中的细胞因子，并与肾功能相关联。对 40 个颈动脉斑块进行定量蛋白质组学分析，并与肾功能相关联。
肾功能下降与斑块内出血的比值比（OR）增加（OR 1.15；95%CI：1.02-1.29；p=0.024）和纤维粥样硬化斑块（脂质核心占总斑块表面 10%以上的斑块）的比值比（OR）增加（OR 1.21；95%CI：1.07-1.38；p=0.003）相关，eGFR 每降低 20 分。蛋白质组学研究表明，肾功能下降与经典补体途径和内在凝血途径的上调相关。
肾功能下降与斑块出血相关，而与炎症斑块特征无关。我们的数据表明，在肾功能下降的患者中，与炎症途径无关的其他途径可能与斑块易损性和不良预后相关。
