ABSTRACT

To characterize atherogenesis functionally, we studied the functional heterogeneity of endotheliocytes in carotid vessels with atherosclerotic plaques and identified several distinct cell clusters. We measured the Ki-67 labeling index (Ki-67 LI), percentage of Bcl-2 cells (CP) and expression of CCL5, IL 6 and VCAM1 in each cell cluster. We also investigated how these indicators change when the plaque becomes unstable and how they affect the risk of adverse cerebrovascular events in patients. We evaluated the inter-cluster gradient of marker activity and its relation to patient prognosis. We identified five endothelial clusters: the under plaque cluster (UPC), peripheral cluster (PC), marginal cluster (MC), transient cluster (TC) and outside plaque cluster (OC). The UPC exhibited the greatest proliferative, proinflammatory and adhesive activity, but low anti-apoptotic activity. The PC exhibited the second greatest proliferative, adhesive and proinflammatory activity. Progression of atherosclerosis and transition of a stable atherosclerotic plaque to an unstable one was accompanied by increased expression of nearly all markers. The proliferative activity in the UPC, PC and OC, and the pro-inflammatory activity in UPC and anti-apoptotic activity in the PC, were correlated with prognosis. Also, two gradients of proliferative activity and a gradient of pro-inflammatory activity were associated with risk of adverse events.

摘要

为了在功能上表征动脉粥样硬化，我们研究了具有动脉粥样硬化斑块的颈动脉血管中内皮细胞的功能异质性，并确定了几个不同的细胞簇。我们测量了每个细胞簇中的 Ki-67 标记指数 (Ki-67 LI)、Bcl-2 细胞 (CP) 的百分比和 CCL5、IL 6 和 VCAM1 的表达。我们还研究了当斑块变得不稳定时这些指标如何变化，以及它们如何影响患者发生不良脑血管事件的风险。我们评估了标志物活性的簇间梯度及其与患者预后的关系。我们确定了五个内皮簇：斑块下簇 (UPC)、外周簇 (PC)、边缘簇 (MC)、瞬时簇 (TC) 和斑块外簇 (OC)。UPC 表现出最大的增殖、促炎和粘附活性，但抗凋亡活性低。PC 表现出第二大的增殖、粘附和促炎活性。动脉粥样硬化的进展和稳定的动脉粥样硬化斑块向不稳定的动脉粥样硬化斑块的转变伴随着几乎所有标志物的表达增加。UPC、PC 和 OC 的增殖活性以及 UPC 的促炎活性和 PC 的抗凋亡活性与预后相关。此外，增殖活性的两个梯度和促炎活性的梯度与不良事件的风险相关。动脉粥样硬化的进展和稳定的动脉粥样硬化斑块向不稳定的动脉粥样硬化斑块的转变伴随着几乎所有标志物的表达增加。UPC、PC 和 OC 的增殖活性以及 UPC 的促炎活性和 PC 的抗凋亡活性与预后相关。此外，增殖活性的两个梯度和促炎活性的梯度与不良事件的风险相关。动脉粥样硬化的进展和稳定的动脉粥样硬化斑块向不稳定的动脉粥样硬化斑块的转变伴随着几乎所有标志物的表达增加。UPC、PC 和 OC 的增殖活性以及 UPC 的促炎活性和 PC 的抗凋亡活性与预后相关。此外，增殖活性的两个梯度和促炎活性的梯度与不良事件的风险相关。