Remnant lipoproteins from patients with sudden cardiac death enhance coronary vasospastic activity through upregulation of Rho-kinase
Remnant lipoproteins from patients with sudden cardiac death enhance coronary vasospastic activity through upregulation of Rho-kinase
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DOI：
10.1161/01.atv.0000126678.93747.80
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发表时间：
2004-05-01
影响因子：
8.7
通讯作者：
Takeshita, A
中科院分区：
文献类型：
--
作者：
Oi, K;Shimokawa, H;Takeshita, A
心脏性猝死（SCD）仍然是一个严重的问题。我们以前已经证明，残粒样颗粒（RLP）是SCD的主要危险因素，Rho激酶在冠状动脉血管痉挛的分子机制中起着核心作用。在这项研究中，我们研究了RLP从SCD患者是否上调Rho激酶与增强冠状动脉vasspastic activity.Methods和Results-We分离RLP和非RLP在极低密度脂蛋白（VLDL）馏分SCD患者无冠状动脉狭窄。我们进行了体内研究，其中我们在猪的外膜处用RLP或非RLP组分处理冠状动脉。1周后，5-羟色胺在RLP组引起明显的冠状动脉过度收缩（P < 0.001，n = 6），而非RLP组则无明显变化（P> 0.001，n = 6）。在器官室实验中，5-羟色胺引起RLP处理的血管平滑肌细胞（VSMC）的过度收缩，羟法舒地尔显著抑制这种收缩（P < 0.001，n = 6）。在体外培养的人冠状动脉VSMC中，RLP可显著增强Rho激酶的表达和活性（P < 0.05，n = 6）。
Objective-Sudden cardiac death (SCD) still remains a serious problem. We have previously shown that remnant-like particles (RLP) are the major risk factor for SCD and that Rho-kinase plays a central role in the molecular mechanism of coronary vasospasm. In this study, we examined whether RLP from patients with SCD upregulate Rho-kinase associated with an enhanced coronary vasospastic activity.Methods and Results-We isolated RLP and non-RLP in very-low-density lipoprotein (VLDL) fraction from SCD patients without coronary stenosis. We performed in vivo study in which we treated the coronary artery with RLP or non-RLP fraction at the adventitia in pigs. After 1 week, intracoronary serotonin caused marked coronary hyperconstriction at the segment treated with RLP fraction but not with non-RLP fraction (P < 0.001, n = 6), and hydroxyfasudil, a selective Rho-kinase inhibitor, dose-dependently inhibited the spasm in vivo. In organ chamber experiments, serotonin caused hypercontraction of vascular smooth muscle cells (VSMC) from RLP-treated segment, which was significantly inhibited by hydroxyfasudil (P < 0.001, n = 6). In cultured human coronary VSMC, the treatment with RLP significantly enhanced the expression and activity of Rho-kinase (P < 0.05, n = 6).Conclusions-These results indicate that RLP from SCD patients upregulate Rho-kinase in coronary VSMC and markedly enhance coronary vasospastic activity.