Leptin Locally Synthesized in Carotid Atherosclerotic Plaques Could Be Associated With Lesion Instability and Cerebral Emboli
Leptin Locally Synthesized in Carotid Atherosclerotic Plaques Could Be Associated With Lesion Instability and Cerebral Emboli
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DOI：
10.1161/jaha.112.001727
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发表时间：
2012-10-01
影响因子：
5.4
通讯作者：
Virmani, Renu
中科院分区：
文献类型：
--
作者：
Schneiderman, Jacob;Schaefer, Katrin;Virmani, Renu
背景-不稳定的颈动脉斑块会导致脑栓塞。瘦素促进动脉粥样硬化和血管壁重塑。我们假设颈动脉粥样硬化病变不稳定与局部瘦素合成有关。方法和结果 - 对有症状（n = 40）和无症状进行性狭窄患者（n = 38）的颈动脉内膜切除术斑块进行分析，了解瘦素、肿瘤坏死因子（TNF）-α和纤溶酶原激活剂抑制剂1型的局部表达。所有病变均表现出晚期动脉粥样硬化，包括厚帽和薄帽纤维粥样斑块或病变破裂。有症状的病变表现出更多的斑块破裂和巨噬细胞浸润（分别为P=0.001和P=0.05）。有症状的斑块优先显示瘦素、TNF-α 和纤溶酶原激活剂抑制剂 1 型转录物（分别为 P=0.03、P=0.04 和 P=0.05）。通过原位杂交和免疫组织化学证实巨噬细胞和平滑肌细胞中的瘦素mRNA和抗原。各组之间血浆瘦素水平没有显着差异（P=1.0），而有症状患者的TNF-α水平显着升高（P=0.006）。 TNF-α、脂多糖或脂磷壁酸刺激的人主动脉平滑肌细胞培养物显示，72 小时时，分泌的瘦素抗原分别增加了 6、6.7 和 6 倍（P
Background-Unstable carotid plaques cause cerebral emboli. Leptin promotes atherosclerosis and vessel wall remodeling. We hypothesized that carotid atherosclerotic lesion instability is associated with local leptin synthesis.Methods and Results-Carotid endarterectomy plaques from symptomatic (n=40) and asymptomatic patients with progressive stenosis (n=38) were analyzed for local expression of leptin, tumor necrosis factor (TNF)-alpha, and plasminogen activator inhibitor type 1. All lesions exhibited advanced atherosclerosis inclusive of thick-and thin-cap fibroatheromas or lesion rupture. Symptomatic lesions exhibited more plaque ruptures and macrophage infiltration (P=0.001 and P=0.05, respectively). Symptomatic plaques showed preferential leptin, TNF-alpha, and plasminogen activator inhibitor type 1 transcript (P=0.03, P=0.04, and P=0.05, respectively). Leptin mRNA and antigen in macrophages and smooth muscle cells were confirmed by in situ hybridization and immunohistochemistry. Plasma leptin levels were not significantly different between groups (P=1.0), whereas TNF-alpha was significantly increased in symptomatic patients (P=0.006). Human aortic smooth muscle cell culture stimulated by TNF-alpha, lipopolysaccharide, or lipoteichoic acid revealed 6-, 6.7-, and 6-fold increased secreted leptin antigen, respectively, at 72 hours (P