Acute and chronic exposure to shear stress have opposite effects on endothelial permeability to macromolecules
Acute and chronic exposure to shear stress have opposite effects on endothelial permeability to macromolecules
复制标题
DOI：
10.1152/ajpheart.00114.2010
复制
发表时间：
2010-06-01
影响因子：
4.8
通讯作者：
Weinberg, Peter D.
中科院分区：
文献类型：
--
作者：
Warboys, Christina M.;Berson, R. Eric;Weinberg, Peter D.
Warboys CM、Berson RE、Mann GE、Pearson JD、Weinberg PD。急性和慢性暴露于剪切应力对内皮对大分子的通透性具有相反的影响。 Am J Physiol Heart Circ Physiol 298：H1850-H1856，2010。首次发表于 2010 年 4 月 2 日； doi:10.1152/ajpheart.00114.2010.-内皮特性受机械应力影响。多项研究表明，强烈施加剪切应力会增加培养物中内皮单层的渗透性。我们研究了更长时间的剪切作用是否会产生相反的效果。在 Transwell 滤器上培养猪主动脉内皮细胞，以评估单层对白蛋白的通透性。使用轨道摇床旋转细胞上方的培养基；计算得出的剪切力处于生理范围内。急性应用剪切会增加渗透性，但长期应用会降低渗透性。通过抑制一氧化氮（NO）的合成，可以逆转慢性而非急性剪切的影响。抑制磷脂酰肌醇 3-OH 激酶 (PI3K) 和可溶性鸟苷酸环化酶也可以逆转慢性剪切的影响。这些干预措施均不会影响静态条件下的渗透性，并且环氧合酶的抑制也没有效果。慢性剪切使有丝分裂率降低的程度与通透性的降低相当，但这种效应并不能通过抑制 NO 合成而逆转。我们得出结论，长期施加剪切应力可通过 PI3K-NO-cGMP 依赖性机制降低内皮对大分子的通透性。由于血浆大分子过度进入动脉壁可能引发动脉粥样硬化，因此这种现象可能有助于解释剪切力和一氧化氮的动脉粥样硬化保护作用。
Warboys CM, Berson RE, Mann GE, Pearson JD, Weinberg PD. Acute and chronic exposure to shear stress have opposite effects on endothelial permeability to macromolecules. Am J Physiol Heart Circ Physiol 298: H1850-H1856, 2010. First published April 2, 2010; doi:10.1152/ajpheart.00114.2010.-Endothelial properties are affected by mechanical stresses. Several studies have shown that an acute application of shear stress increases the permeability of endothelial monolayers in culture. We investigated whether more prolonged application of shear has the opposite effect. Porcine aortic endothelial cells were cultured on Transwell filters to assess monolayer permeability to albumin. The medium above the cells was swirled using an orbital shaker; resultant shears were computed to lie within the physiological range. Acute application of shear increased permeability, but chronic application reduced it. The effect of chronic but not acute shear was reversed by inhibiting nitric oxide (NO) synthesis. The effect of chronic shear was also reversed by inhibiting phosphatidylinositol 3-OH kinase (PI3K) and soluble guanylyl cyclase. None of these interventions affected permeability under static conditions, and inhibition of cyclooxygenase was without effect. Chronic shear decreased mitosis rates by a fraction comparable to the reduction in permeability, but this effect was not reversed by inhibiting NO synthesis. We conclude that chronic application of shear stress reduces endothelial permeability to macromolecules by a PI3K-NO-cGMP-dependent mechanism. Since atherosclerosis can be triggered by excessive entry of plasma macromolecules into the arterial wall, the phenomenon may help explain the atheroprotective effects of shear and NO.