Mechanical properties of the extracellular matrix alter expression of smooth muscle protein LPP and its partner palladin; relationship to early atherosclerosis and vascular injury.

Mechanical properties of the extracellular matrix alter expression of smooth muscle protein LPP and its partner palladin; relationship to early atherosclerosis and vascular injury.
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DOI:
10.1007/s10974-009-9173-1
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发表时间:
2009
影响因子:
2.7
通讯作者:
Somlyo, Avril V.
Somlyo, Avril V.
中科院分区:
生物学3区
文献类型:
--
作者:
Jin, Li;Hastings, Nicole E.;Blackman, Brett R.;Somlyo, Avril V.

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脂肪瘤首选伴侣(LPP)定位于局灶性粘连/致密小体,选择性表达于平滑肌细胞(SMC),促进细胞迁移。在变性胶原或刚性基质上培养的SMC,LPP、其伴侣Palladin、TN-C、磷酸化粘着斑激酶(PFAK)的表达上调,表现出较强的应激纤维。在内皮(EC)/SMC血流动力学系统中,模拟动脉粥样硬化血流的剪应力波形作用于EC层,显著降低SMC LPP和Palladin的表达。在动脉粥样硬化和氧化应激的ApoE小鼠模型中,TN-C也下调了它们的表达,但在动脉损伤模型中,它们的表达随着pFAK、PRX1和TN-C的上游顺序变化而上调。综上所述,LPP和Palladin的表达受机械信号、氧化应激和底物组成的共同调控,在血管壁损伤和早期动脉粥样硬化形成过程中,LPP和Palladin表达上调或下调。
Lipoma preferred partner (LPP) localizes to focal adhesions/dense bodies, is selectively expressed in smooth muscle cells (SMC) and enhances cell migration. SMCs cultured on denatured collagen or on a rigid substrate, up regulated expression of LPP, its partner palladin, tenascin C (TN-C), phosphorylated focal adhesion kinase (pFAK) and exhibited robust stress fibers. In an endothelial (EC) /SMC hemodynamic flow system, shear stress waveforms mimicking atheroprone flow, applied to the EC layer, significantly decreased expression of SMC LPP and palladin. They were also down regulated with TN-C, in an ApoE murine model of atherosclerosis and with oxidative stress but up regulated in an arterial injury model in response to upstream sequential changes in pFAK, Prx1 and TN-C. In conclusion, expression of LPP and palladin are modulated by a mix of mechanical cues, oxidative stress and substrate composition which translate into their up or down regulation in vessel wall injury and early atherogenesis.
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