Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension
Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension
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DOI：
10.1073/pnas.0405908101
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发表时间：
2004-09-21
影响因子：
11.1
通讯作者：
Yuan, JXJ
中科院分区：
文献类型：
--
作者：
Yu, Y;Fantozzi, L;Yuan, JXJ
肺动脉平滑肌细胞(PASMC)过度增殖引起的肺血管中层肥大是特发性肺动脉高压(IPAH)患者肺血管阻力升高的主要原因。钙内流增加是PASMC增殖的重要刺激因素。瞬时受体电位(Trp)通道基因编码的钙通道在细胞增殖过程中负责钙离子的进入。正常人PASMC表达多种典型色氨酸(TRPC)亚型，TRPC6高表达，TRPC3低表达。正常PASMC中TRPC6的蛋白表达与Ki67的表达密切相关，提示TRPC6的表达参与了PASMC从静止期向有丝分裂的转变。在IPAH患者肺组织和PASMC中，TRPC3和-6mRNA和蛋白的表达明显高于正常血压和继发性肺动脉高压患者。TRPC6小干扰RNA抑制TRPC6的表达可明显抑制Ipah-PASMC的增殖。这些结果表明，TRPC通道的表达与PASMC的细胞周期进程有关。TRPC通道过度表达可能是IPAH患者PASMC增殖增加和肺血管中层肥厚的部分原因。
Pulmonary vascular medial hypertrophy caused by excessive pulmonary artery smooth muscle cell (PASMC) proliferation is a major cause for the elevated pulmonary vascular resistance in patients with idiopathic pulmonary arterial hypertension (IPAH). Increased Ca2+ influx is an important stimulus for PASMC proliferation. Transient receptor potential (TRP) channel genes encode Ca2+ channels that are responsible for Ca2+ entry during cell proliferation. Normal human PASMC expressed multiple canonical TRP (TRPC) isoforms; TRPC6 was highly expressed and TRPC3 was minimally expressed. The protein expression of TRPC6 in normal PASMC closely correlated with the expression of Ki67, suggesting that TRPC6 expression is involved in the transition of PASMC from quiescent phase to mitosis. In lung tissues and PASMC from IPAH patients, the mRNA and protein expression of TRPC3 and -6 were much higher than in those from normotensive or secondary pulmonary hypertension patients. Inhibition of TRPC6 expression with TRPC6 small interfering RNA markedly attenuated IPAH-PASMC proliferation. These results demonstrate that expression of TRPC channels correlates with the progression of the cell cycle in PASMC. TRPC channel overexpression may be partially responsible for the increased PASMC proliferation and pulmonary vascular medial hypertrophy in IPAH patients.