Remnant Lipoproteins from Patients with Sudden Cardiac Death Enhance Coronary Vasospastic Activity Through Upregulation of Rho-Kinase

Keiji Oi, Hiroaki Shimokawa, Junko Hiroki, Toyokazu Uwatoku, Kohtaro Abe, Yasuharu Matsumoto, Yasuhiro Nakajima, Katsuyuki Nakajima, Sanae Takeichi, Akira Takeshita

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)918-922
Number of pages5
JournalArteriosclerosis, thrombosis, and vascular biology
Volume24
Issue number5
DOIs
Publication statusPublished - 2004 May

Keywords

  • Coronary vasospasm
  • Lipoproteins
  • Sudden cardiac death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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