Profilin-1 is expressed in human atherosclerotic plaques and induces atherogenic effects on vascular smooth muscle cells.
Profilin-1 is expressed in human atherosclerotic plaques and induces atherogenic effects on vascular smooth muscle cells.
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DOI：
10.1371/journal.pone.0013608
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发表时间：
2010-10-25
期刊：
影响因子：
3.7
通讯作者：
Rosenkranz S
中科院分区：
文献类型：
--
作者：
Caglayan E;Romeo GR;Kappert K;Odenthal M;Südkamp M;Body SC;Shernan SK;Hackbusch D;Vantler M;Kazlauskas A;Rosenkranz S
Profilin-1是一种普遍存在的肌动蛋白结合蛋白。在糖尿病等病理条件下，血管内皮中的profilin-1水平增加。我们最近证实，profilin-1过表达触发LDL信号下游内皮功能障碍的指标，并且profilin-1的表达减弱可在体内保护动脉粥样硬化。在这里，我们监测profilin-1在人类动脉粥样硬化斑块的免疫荧光染色的表达。在培养的大鼠主动脉和人冠状动脉血管平滑肌细胞（VSMCs）中评价重组profilin-1对致动脉粥样硬化信号通路和细胞反应如DNA合成（BrdU掺入）和趋化性（改良Boyden室）的影响。此外，在人类中评估了profilin-1血清水平与动脉粥样硬化程度之间的相关性。在冠心病患者的冠状动脉中，我们发现与正常血管壁相比，动脉粥样硬化斑块中的profilin表达显著增强。在体外用重组profilin-1（10−6 M）刺激大鼠主动脉和人冠状动脉VSMC，导致细胞内信号级联激活，如10分钟内Erk 1/2、p70 S6激酶和PI 3 K/Akt磷酸化。此外，profilin-1浓度依赖性诱导大鼠和人VSMCs的DNA合成和迁移，分别。抑制PI 3 K（Wortmannin，LY 294002）或Src家族激酶（SU 6656，PP 2），但不是PLCγ（U 73122），完全消除了profilin诱导的细胞周期进程，而PI 3 K抑制部分降低了趋化反应。最后，我们发现，在人类严重动脉粥样硬化患者中，profilin-1血清水平显著升高（p<0.001，与无动脉粥样硬化或对照组相比）。与正常血管壁相比，人动脉粥样硬化斑块中的Profilin-1表达显著增强，并且profilin-1的血清水平与人动脉粥样硬化的程度相关。profilin-1对VSMC的致动脉粥样硬化作用表明斑块内的自分泌/旁分泌作用。这些数据表明profilin-1可能对动脉粥样硬化的形成有重要作用，并可能代表一种新的治疗靶点。
Profilin-1 is an ubiquitous actin binding protein. Under pathological conditions such as diabetes, profilin-1 levels are increased in the vascular endothelium. We recently demonstrated that profilin-1 overexpression triggers indicators of endothelial dysfunction downstream of LDL signaling, and that attenuated expression of profilin-1 confers protection from atherosclerosis in vivo. Here we monitored profilin-1 expression in human atherosclerotic plaques by immunofluorescent staining. The effects of recombinant profilin-1 on atherogenic signaling pathways and cellular responses such as DNA synthesis (BrdU-incorporation) and chemotaxis (modified Boyden-chamber) were evaluated in cultured rat aortic and human coronary vascular smooth muscle cells (VSMCs). Furthermore, the correlation between profilin-1 serum levels and the degree of atherosclerosis was assessed in humans. In coronary arteries from patients with coronary heart disease, we found markedly enhanced profilin expression in atherosclerotic plaques compared to the normal vessel wall. Stimulation of rat aortic and human coronary VSMCs with recombinant profilin-1 (10−6 M) in vitro led to activation of intracellular signaling cascades such as phosphorylation of Erk1/2, p70S6 kinase and PI3K/Akt within 10 minutes. Furthermore, profilin-1 concentration-dependently induced DNA-synthesis and migration of both rat and human VSMCs, respectively. Inhibition of PI3K (Wortmannin, LY294002) or Src-family kinases (SU6656, PP2), but not PLCγ (U73122), completely abolished profilin-induced cell cycle progression, whereas PI3K inhibition partially reduced the chemotactic response. Finally, we found that profilin-1 serum levels were significantly elevated in patients with severe atherosclerosis in humans (p<0.001 vs. no atherosclerosis or control group). Profilin-1 expression is significantly enhanced in human atherosclerotic plaques compared to the normal vessel wall, and the serum levels of profilin-1 correlate with the degree of atherosclerosis in humans. The atherogenic effects exerted by profilin-1 on VSMCs suggest an auto-/paracrine role within the plaque. These data indicate that profilin-1 might critically contribute to atherogenesis and may represent a novel therapeutic target.
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影响因子：
7.7
作者：
Caglayan E;Stauber B;Collins AR;Lyon CJ;Yin F;Liu J;Rosenkranz S;Erdmann E;Peterson LE;Ross RS;Tangirala RK;Hsueh WA
通讯作者：
Hsueh WA
影响因子：
64.5
作者：
HAUGWITZ, M;NOEGEL, AA;SCHLEICHER, M
通讯作者：
SCHLEICHER, M
DOI：
10.1096/fj.03-0841fje
发表时间：
2004-04-01
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Romeo, Giulio;Frangioni, John V;Kazlauskas, Andrius
通讯作者：
Kazlauskas, Andrius
影响因子：
20.1
作者：
Walcher, Daniel;Babiak, Christina;Marx, Nikolaus
通讯作者：
Marx, Nikolaus
动脉粥样硬化的炎症。
DOI：
10.1161/atvbaha.108.179705
发表时间：
2012-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Libby P
通讯作者：
Libby P