Thrombospondin-1 inhibition of vascular smooth muscle cell responses occurs via modulation of both cAMP and cGMP.
Thrombospondin-1 inhibition of vascular smooth muscle cell responses occurs via modulation of both cAMP and cGMP.
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血小板传播1对血管平滑肌细胞反应的抑制是通过调节CAMP和CGMP发生的。
DOI：
10.1016/j.phrs.2010.10.014
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发表时间：
2011-01
影响因子：
9.3
通讯作者：
Isenberg, Jeff S.
中科院分区：
文献类型：
--
作者：
Yao, Mingyi;Roberts, David D.;Isenberg, Jeff S.
一氧化氮（NO）驱动血管细胞的促生存反应，限制血小板粘附，增强血流量，减少血栓形成。基质细胞蛋白血小板反应蛋白-1 （TSP1）通过与其受体CD47的相互作用，抑制血管细胞中NO对可溶性鸟酰环化酶（sGC）的激活。在血管平滑肌细胞（VSMCs）中，细胞内cGMP和cAMP共同调节黏附、收缩、增殖和迁移。cGMP可以通过反馈控制水解来调节cAMP。cAMP磷酸二酯酶-4的抑制选择性地干扰了外源性TSP1阻断no驱动的VSMC粘附的能力，但不影响cGMP的积累，这表明cAMP也参与了TSP1对VSMC的调节。抑制磷酸二酯酶-4足以提高cAMP水平，抑制胍基环化酶或磷酸二酯酶-3，或添加外源性TSP1可逆转cAMP的升高。因此，TSP1部分通过cgmp依赖性抑制磷酸二酯酶-3来调节VSMC cAMP水平。此外，在TSP1缺失小鼠的VSMCs和骨骼肌中，基础cAMP水平持续升高，并且用外源性TSP1处理缺失细胞抑制cAMP水平与野生型细胞相同。TSP1抑制福斯克林和异丙肾上腺素刺激的VSMCs cAMP升高。TSP1还消除了福斯克林和异丙肾上腺素刺激的血管舒张。与其直接限制腺苷酸环化酶激活的血管舒张的能力一致，TSP1也限制camp诱导的肌球蛋白轻链-2的去磷酸化。这些发现表明，TSP1通过磷酸二酯酶依赖的第二信使间的串导和腺苷酸环化酶激活的抑制，限制了cGMP和cAMP信号通路以及VSMCs和动脉的功能反应。
Nitric oxide (NO) drives pro-survival responses in vascular cells and limits platelet adhesion, enhancing blood flow and minimizing thrombosis. The matricellular protein thrombospondin-1 (TSP1), through interaction with its receptor CD47, inhibits soluble guanylyl cyclase (sGC) activation by NO in vascular cells. In vascular smooth muscle cells (VSMCs) both intracellular cGMP and cAMP regulate adhesion, contractility, proliferation, and migration. cGMP can regulate cAMP through feedback control of hydrolysis. Inhibition of the cAMP phosphodiesterase-4 selectively interfered with the ability of exogenous TSP1 to block NO-driven VSMC adhesion but not cGMP accumulation, suggesting that cAMP also contributes to VSMC regulation by TSP1. Inhibition of phosphodiesterase-4 was sufficient to elevate cAMP levels, and inhibiting guanylyl cyclase or phosphodiesterase-3, or adding exogenous TSP1 reversed this increase in cAMP. Thus, TSP1 regulates VSMC cAMP levels in part via cGMP-dependent inhibition of phosphodiesterase-3. Additionally basal cAMP levels were consistently elevated in both VSMCs and skeletal muscle from TSP1 null mice, and treating null cells with exogenous TSP1 suppressed cAMP levels to those of wild type cells. TSP1 inhibited both forskolin and isoproterenol stimulated increases in cAMP in VSMCs. TSP1 also abrogated forskolin and isoproterenol stimulated vasodilation. Consistent with its ability to directly limit adenylyl cyclase-activated vasodilation, TSP1 also limited cAMP-induced dephosphorylation of myosin light chain-2. These findings demonstrate that TSP1 limits both cGMP and cAMP signaling pathways and functional responses in VSMCs and arteries, by both phosphodiesterase-dependent cross talk between these second messengers and by inhibition of adenylyl cyclase activation.
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影响因子：
4.8
作者：
Frazier, WA;Gao, AG;Linder, ME
通讯作者：
Linder, ME
DOI：
10.1016/j.matbio.2009.01.002
发表时间：
2009-03
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
--
作者：
Isenberg JS;Qin Y;Maxhimer JB;Sipes JM;Despres D;Schnermann J;Frazier WA;Roberts DD
通讯作者：
Roberts DD
影响因子：
7.3
作者：
BOULANGER, C;SCHINI, VB;VANHOUTTE, PM
通讯作者：
VANHOUTTE, PM
影响因子：
4.8
作者：
Isenberg, Jeff S.;Jia, Yifeng;Roberts, David D.
通讯作者：
Roberts, David D.
影响因子：
6.9
作者：
Isenberg, JS;Calzada, MJ;Roberts, DD
通讯作者：
Roberts, DD