Cyclooxygenase-2 induction by bradykinin in aortic vascular smooth muscle cells.
Cyclooxygenase-2 induction by bradykinin in aortic vascular smooth muscle cells.
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主动脉血管平滑肌细胞中缓激肽诱导环氧合酶-2。
DOI：
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
V. Velarde
中科院分区：
文献类型：
--
作者：
Jorge A. Rodriguez;Paula de la Cerda;E. Collyer;Valerie Decap;C. Vio;V. Velarde
血管平滑肌细胞增殖和迁移在包括动脉粥样硬化在内的多种血管疾病的病理生理学中起重要作用。参与该过程的前列腺素由两种环氧合酶（考克斯）同工型合成，其中受调节的考克斯-2同工型的表达在动脉粥样硬化斑块中增加。缓激肽（BK）是一种在炎症中增加的血管活性肽，通过特异性受体激活诱导胰头素的形成。我们推测BK在调节考克斯-2中起重要作用，有助于血管平滑肌细胞中的三尖杉酯碱产生的增加。在此，我们研究了参与BK对原代培养的主动脉血管平滑肌细胞中考克斯-2蛋白水平调节的信号通路。我们观察到BK诱导的考克斯-2蛋白水平增加，在24 h达到最大。这种增加被B2激肽受体拮抗剂阻断，但不是B1受体拮抗剂，表明B2受体参与了这一途径。此外，我们得出结论，丝裂原活化蛋白激酶p42/p44，蛋白激酶C和一氧化氮合酶的激活是必要的，增加考克斯-2水平诱导BK，因为这些酶的特异性抑制剂阻断BK的效果。使用类似的方法，我们进一步证明，活性氧和cAMP不是介导的这一途径。这些结果表明，BK激活几种细胞内途径，这些途径联合作用以增加考克斯-2蛋白水平。这项研究表明BK通过控制考克斯-2的水平在动脉粥样硬化斑块的演变中发挥作用。
Vascular smooth muscle cell proliferation and migration play an important role in the pathophysiology of several vascular diseases, including atherosclerosis. Prostaglandins that have been implicated in this process are synthesized by two isoforms of cyclooxygenase (COX), with the expression of the regulated COX-2 isoform increased in atherosclerotic plaques. Bradykinin (BK), a vasoactive peptide increased in inflammation, induces the formation of prostaglandins through specific receptor activation. We hypothesized that BK plays an important role in the regulation of COX-2, contributing to the increase in production of prostaglandins in vascular smooth muscle cells. Herein we examined the signaling pathways that participate in the BK regulation of COX-2 protein levels in primary cultured aortic vascular smooth muscle cells. We observed an increase in COX-2 protein levels induced by BK that was maximal at 24 h. This increase was blocked by a B2 kinin receptor antagonist but not a B1 receptor antagonist, suggesting that the B2 receptor is involved in this pathway. In addition, we conclude that the activation of mitogen-activated protein kinases p42/p44, protein kinase C, and nitric oxide synthase is necessary for the increase in COX-2 levels induced by BK because either of the specific inhibitors for these enzymes blocked the effect of BK. Using a similar approach, we further demonstrated that reactive oxygen species and cAMP were not mediators on this pathway. These results suggest that BK activates several intracellular pathways that act in combination to increase COX-2 protein levels. This study suggests a role for BK on the evolution of the atheromatous plaque by virtue of controlling the levels of COX-2.
血管平滑肌细胞中缓激肽激活 MAPK 的机制。
DOI：
10.1152/ajpcell.1999.277.2.c253
发表时间：
1999
期刊：
The American journal of physiology
影响因子：
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作者：
Velarde,V;Ullian,ME;Morinelli,TA;Mayfield,RK;Jaffa,AA
通讯作者：
Jaffa,AA
NOS 和小窝蛋白在仓鼠外周脉管系统和骨骼肌中的共同分布。
DOI：
10.1152/ajpheart.1999.277.3.h1167
发表时间：
1999
期刊：
The American journal of physiology
影响因子：
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作者：
Segal,SS;Brett,SE;Sessa,WC
通讯作者：
Sessa,WC
DOI：
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发表时间：
2001-04
期刊：
Journal of the American Society of Nephrology : JASN
影响因子：
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作者：
C. Vio;S. An;C. Céspedes;J. Mcgiff;N. Ferreri
通讯作者：
C. Vio;S. An;C. Céspedes;J. Mcgiff;N. Ferreri