Division of Cardiology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.
Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan.
Atherosclerosis. 2017 Oct;265:283-291. doi: 10.1016/j.atherosclerosis.2017.06.920. Epub 2017 Jun 23.
Glucagon-like peptide-1 (GLP-1) is thought to inhibit development of aortic atherosclerosis and plaque formation. However, whether GLP-1 stabilizes fully developed atherosclerotic plaque or alters the complicated plaque composition remains unclarified.
Ten Watanabe heritable hyperlipidemic (WHHL) rabbits were divided into GLP-1 receptor agonist treatment group and control group. After confirmation of atherosclerotic plaques in brachiocephalic arteries by iMap intravascular ultrasound (iMAP-IVUS), GLP-1 receptor agonist lixisenatide was administered to WHHL rabbits at 30 nmoL/kg/day for 12 weeks by osmotic pump. An equal volume of normal saline was administered in a control group. After evaluation by iMAP-IVUS at 12 weeks, brachiocephalic arteries were harvested for pathological histological analysis.
iMAP-IVUS analysis revealed larger fibrotic plaque components and smaller necrotic and calcified plaque components in the GLP-1 group than in the control group; %fibrotic area: 66.30 ± 2.06% vs. 75.14 ± 2.62%, p < 0.01, %necrotic area: 23.25 ± 1.87% vs. 16.17 ± 2.27%, p = 0.02, %calcified area: 2.15 ± 0.24% vs. 1.00 ± 0.18%, p < 0.01), indicating that GLP-1 receptor agonist might modify plaque composition and increase plaque stability. Histological analysis confirmed that GLP-1 receptor agonist treatment improved smooth muscle cell (SMC)-rich plaque with increased fibrotic content. Furthermore, plaque macrophage infiltration and calcification were significantly reduced by GLP-1 receptor agonist treatment; %SMC area: 6.93 ± 0.31% vs. 8.14 ± 0.48%, p = 0.02; %macrophage area: 9.11 ± 0.80% vs. 6.19 ± 0.85%, p < 0.01; %fibrotic area: 54.75 ± 1.63% vs. 69.60 ± 2.12%, p = 0.02; %calcified area: 3.25 ± 0.67% vs. 0.75 ± 0.15%, p = 0.02).
GLP-1 receptor agonist inhibited plaque progression and promoted plaque stabilization by inhibiting plaque growth and modifying plaque composition.
胰高血糖素样肽-1（GLP-1）被认为可以抑制主动脉粥样硬化的发展和斑块形成。然而，GLP-1 是否稳定完全形成的动脉粥样硬化斑块，或者改变复杂的斑块组成仍不清楚。
将 10 只 Watanabe 遗传性高脂血症（WHHL）兔分为 GLP-1 受体激动剂治疗组和对照组。通过 iMap 血管内超声（iMAP-IVUS）确认颈总动脉粥样硬化斑块后，GLP-1 受体激动剂利西那肽以 30 nmol/kg/天的剂量通过渗透泵给予 WHHL 兔 12 周。对照组给予等体积生理盐水。12 周后通过 iMAP-IVUS 评估后，采集颈总动脉进行病理组织学分析。
iMAP-IVUS 分析显示 GLP-1 组的纤维斑块成分较大，坏死和钙化斑块成分较小；纤维性区域百分比：66.30±2.06%比 75.14±2.62%，p<0.01，坏死性区域百分比：23.25±1.87%比 16.17±2.27%，p=0.02，钙化性区域百分比：2.15±0.24%比 1.00±0.18%，p<0.01），提示 GLP-1 受体激动剂可能改变斑块成分并增加斑块稳定性。组织学分析证实，GLP-1 受体激动剂治疗可改善富含平滑肌细胞（SMC）的斑块，增加纤维含量。此外，GLP-1 受体激动剂治疗显著减少斑块内巨噬细胞浸润和钙化；SMC 区域百分比：6.93±0.31%比 8.14±0.48%，p=0.02；巨噬细胞区域百分比：9.11±0.80%比 6.19±0.85%，p<0.01；纤维性区域百分比：54.75±1.63%比 69.60±2.12%，p=0.02；钙化性区域百分比：3.25±0.67%比 0.75±0.15%，p=0.02）。
GLP-1 受体激动剂通过抑制斑块生长和改变斑块组成来抑制斑块进展并促进斑块稳定。
