Natriuretic peptide receptor-3 underpins the disparate regulation of endothelial and vascular smooth muscle cell proliferation by C-type natriuretic peptide.
Natriuretic peptide receptor-3 underpins the disparate regulation of endothelial and vascular smooth muscle cell proliferation by C-type natriuretic peptide.
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DOI：
10.1111/j.1476-5381.2011.01400.x
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发表时间：
2011-09
影响因子：
7.3
通讯作者：
Hobbs AJ
中科院分区：
文献类型：
--
作者：
Khambata RS;Panayiotou CM;Hobbs AJ
C型利钠肽（CNP）是一种内皮源性血管舒张剂，在血管系统中发挥抗动脉粥样硬化作用，并从缺血损伤中挽救心肌。CNP的细胞保护作用部分通过Gi偶联利钠肽受体（NPR）3介导。由于GPCR是众所周知的控制细胞增殖，我们研究了NPR 3激活是否是CNP对内皮和血管平滑肌细胞有丝分裂的影响的基础。在体外研究了人脐静脉内皮细胞（HUVEC）、大鼠主动脉平滑肌细胞（RAoSMC）以及NPR 3基因敲除（KO）小鼠的内皮和血管平滑肌细胞的增殖。CNP（1 pM-1 µM）浓度依赖性地促进HUVEC增殖并抑制RAoSMC生长。CNP的促有丝分裂和抗有丝分裂作用被NPR 3拮抗剂M372049（10 µM）和细胞外信号调节激酶（ERK）1/2抑制剂PD 98059（30 µM）阻断，并且在NPR 3 KO小鼠的细胞中不存在。百日咳毒素（100 ng·mL−1）和M372049（10 µM）可抑制CNP对ERK 1/2的激活。在HUVEC中，ERK 1/2激活增强了细胞周期启动子cyclin D1的表达，而在RAoSMC中，ERK 1/2激活增加了细胞周期抑制剂p21 waf 1/cip 1和p27 kip 1的表达。CNP的血管保护作用的一个方面是通过NPR 3依赖性ERK 1/2磷酸化介导的，导致内皮细胞增殖增强和血管平滑肌生长抑制。这一途径可能为逆转内皮损伤和血管平滑肌增生提供了一种创新的方法，这些都是许多血管疾病的特征。
C-type natriuretic peptide (CNP) is an endothelium-derived vasorelaxant, exerting anti-atherogenic actions in the vasculature and salvaging the myocardium from ischaemic injury. The cytoprotective effects of CNP are mediated in part via the Gi-coupled natriuretic peptide receptor (NPR)3. As GPCRs are well-known to control cell proliferation, we investigated if NPR3 activation underlies effects of CNP on endothelial and vascular smooth muscle cell mitogenesis. Proliferation of human umbilical vein endothelial cells (HUVEC), rat aortic smooth muscle cells (RAoSMC) and endothelial and vascular smooth muscle cells from NPR3 knockout (KO) mice was investigated in vitro. CNP (1 pM–1 µM) facilitated HUVEC proliferation and inhibited RAoSMC growth concentration-dependently. The pro- and anti-mitogenic effects of CNP were blocked by the NPR3 antagonist M372049 (10 µM) and the extracellular signal-regulated kinase (ERK) 1/2 inhibitor PD98059 (30 µM) and were absent in cells from NPR3 KO mice. Activation of ERK 1/2 by CNP was inhibited by Pertussis toxin (100 ng·mL−1) and M372049 (10 µM). In HUVEC, ERK 1/2 activation enhanced expression of the cell cycle promoter, cyclin D1, whereas in RAoSMC, ERK 1/2 activation increased expression of the cell cycle inhibitors p21waf1/cip1 and p27kip1. A facet of the vasoprotective profile of CNP is mediated via NPR3-dependent ERK 1/2 phosphorylation, resulting in augmented endothelial cell proliferation and inhibition of vascular smooth muscle growth. This pathway may offer an innovative approach to reversing the endothelial damage and vascular smooth muscle hyperplasia that characterize many vascular disorders.
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DOI：
10.1016/0006-291x(91)90627-j
发表时间：
1991-06-28
影响因子：
3.1
作者：
FURUYA, M;YOSHIDA, M;MATSUO, H
通讯作者：
MATSUO, H
DOI：
10.1016/0735-1097(96)00206-9
发表时间：
1996-09-01
影响因子：
24
作者：
FitzGibbon, GM;Kafka, HP;Burton, JR
通讯作者：
Burton, JR
影响因子：
11.2
作者：
Kanda, S;Miyata, Y;Kanetake, T
通讯作者：
Kanetake, T
DOI：
10.1006/bbrc.1993.1616
发表时间：
1993-05-28
影响因子：
3.1
作者：
FURUYA, M;AISAKA, K;MATSUO, H
通讯作者：
MATSUO, H
影响因子：
8.7
作者：
Doi, K;Ikeda, T;Nakao, K
通讯作者：
Nakao, K