Caspase-1 Plays a Critical Role in Accelerating Chronic Kidney Disease-Promoted Neointimal Hyperplasia in the Carotid Artery.
Caspase-1 Plays a Critical Role in Accelerating Chronic Kidney Disease-Promoted Neointimal Hyperplasia in the Carotid Artery.
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DOI：
10.1007/s12265-016-9683-3
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发表时间：
2016-04
影响因子：
3.4
通讯作者：
Choi, Eric T.
中科院分区：
文献类型：
--
作者：
Ferrer, Lucas M.;Monroy, Alexandra M.;Lopez-Pastrana, Jahaira;Nanayakkara, Gayani;Cueto, Ramon;Li, Ya-feng;Li, Xinyuan;Wang, Hong;Yang, Xiao-feng;Choi, Eric T.
关键词：
为了确定Caspase-1在慢性肾脏病(CKD)介导的动脉新生内膜增生(NH)中是否起关键作用，我们利用Caspase−/−小鼠，在慢性肾脏病环境中诱导颈动脉新生内膜增生，并用尿毒症血清刺激人血管平滑肌细胞。我们发现：(1)Caspase-1抑制纠正了尿毒症血清介导的VSMC收缩标志物的下调，(2)CKD促进的NH在Caspase−/−小鼠中被减弱，(3)CKD介导的收缩标志物的下调在Caspase阴性小鼠中得到挽救，(4)Caspase-−/−组织中VSMC迁移分子αvβ3整合素的表达减少。我们的结果提示caspase-1途径感知CKD代谢危险信号。此外，CKD介导的VSMC收缩标志物的增加和NH形成中VSMC迁移分子αvβ3整合素的表达增加依赖于Caspase1。因此，caspase-1是抑制CKD促进的NH的一个新的治疗靶点。
To determine whether caspase-1 is critical in chronic kidney disease (CKD)-mediated arterial neointimal hyperplasia (NH), we utilized caspase−/− mice and induced NH in carotid artery in a CKD environment, and uremic sera-stimulated human vascular smooth muscle cells (VSMC). We made the following findings: (1) Caspase-1 inhibition corrected uremic sera-mediated downregulation of VSMC contractile markers, (2) CKD-promoted NH was attenuated in caspase−/− mice, (3) CKD-mediated downregulation of contractile markers was rescued in caspase null mice, and (4) expression of VSMC migration molecule αvβ3 integrin was reduced in caspase−/− tissues. Our results suggested that caspase-1 pathway senses CKD metabolic danger signals. Further, CKD-mediated increase of contractile markers in VSMC and increased expression of VSMC migration molecule αvβ3 integrin in NH formation were caspase-1 dependent. Therefore, caspase-1 is a novel therapeutic target for the suppression of CKD-promoted NH.
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影响因子：
2.9
作者：
Lee T;Roy-Chaudhury P
通讯作者：
Roy-Chaudhury P
影响因子：
3.4
作者：
Daniels, Susan E.;Beineke, Philip;Rhees, Brian;McPherson, John A.;Kraus, William E.;Thomas, Gregory S.;Rosenberg, Steven
通讯作者：
Rosenberg, Steven
DOI：
10.2741/4383
发表时间：
2016-01-01
期刊：
Frontiers in bioscience (Landmark edition)
影响因子：
--
作者：
Li YF;Huang X;Li X;Gong R;Yin Y;Nelson J;Gao E;Zhang H;Hoffman NE;Houser SR;Madesh M;Tilley DG;Choi ET;Jiang X;Huang CX;Wang H;Yang XF
通讯作者：
Yang XF
影响因子：
4.8
作者：
Lopez-Pastrana, Jahaira;Ferrer, Lucas M.;Yang, Xiao-Feng
通讯作者：
Yang, Xiao-Feng
影响因子：
15.9
作者：
Regan, CP;Adam, PJ;Owens, GK
通讯作者：
Owens, GK