This Article Full Text Full Text (PDF) All Versions of this Article: 24/5/918    most recent 01.ATV.0000126678.93747.80v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Oi, K. Articles by Takeshita, A. Search for Related Content PubMed PubMed Citation Articles by Oi, K. Articles by Takeshita, A. Related Collections Animal models of human disease Acute coronary syndromes Coronary circulation

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:918.)
© 2004 American Heart Association, Inc.

Vascular Biology

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

From the Department of Cardiovascular Medicine (K.O., H.S., J.H., T.U., K.A., Y.M., A.T.), Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; Kyushu University COE Program on Lifestyle-Related Diseases (H.S.), Fukuoka, Japan; Department of Forensic Medicine (Y.N., S.T.), Tokai University School of Medicine, Isehara, Japan; and Immunoresearch Laboratories Co (K.N.), Takasaki, Japan.

Correspondence to Dr Hiroaki Shimokawa, Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail shimo{at}cardiol.med.kyushu-u.ac.jp

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.

Key Words: sudden cardiac death • lipoproteins • coronary vasospasm

This article has been cited by other articles:

				B. Bermudez, S. Lopez, Y. M. Pacheco, J. Villar, F. J.G. Muriana, J. D. Hoheisel, A. Bauer, and R. Abia Influence of postprandial triglyceride-rich lipoproteins on lipid-mediated gene expression in smooth muscle cells of the human coronary artery Cardiovasc Res, July 15, 2008; 79(2): 294 - 303. [Abstract] [Full Text] [PDF]

				H. Shimokawa and A. Takeshita Rho-Kinase Is an Important Therapeutic Target in Cardiovascular Medicine Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): 1767 - 1775. [Abstract] [Full Text] [PDF]