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(Circulation. 2000;101:e192.)
© 2000 American Heart Association, Inc.

Circulation Electronic Pages

Calcium Channel Blockers Activate the Interleukin-6 Gene Via the Transcription Factors NF-IL6 and NF-B in Primary Human Vascular Smooth Muscle Cells

Uichi Ikeda, MD, PhD; Takayuki Ito, MD; Kazuyuki Shimada, MD, PhD

Department of Cardiology, Jichi Medical School, Tochigi, Japan

	Introduction

 
To the Editor:

We read with interest the recent study by Eickelberg et al¹ concerning the activation of the interleukin-6 (IL-6) gene via the transcription factors NF-IL6 and NF-B by calcium channel blockers (CCBs) in human vascular smooth muscle cells (VSMCs). CCBs reduce the severity of experimentally induced atherosclerosis, and some clinical trials suggest that they retard or impede the progression of atherosclerosis in humans. We previously reported that IL-6 stimulates the proliferation of VSMCs.² Thus, the study by Eickelberg et al suggests that CCBs promote atherogenesis by inducing IL-6. However, Eickelberg et al cite the study by Lotz and Guerne.³ In this study, IL-6 induced the expression of the tissue inhibitor of metalloproteinase-1 (TIMP-1), an endogenous inhibitor of matrix metalloproteinases (MMPs), in human connective tissue cells. Eickelberg et al¹ proposed that the local induction of IL-6 in the arterial vessel wall by CCBs essentially reduced atherosclerotic progression by inducing the expression of tissue TIMPs.

CCBs also have direct effects on the expression of MMPs and TIMPs. Indeed, Eickelberg et al⁴ themselves previously reported that CCBs modulated directly MMP-2 activity and inhibited TIMP-2 expression in human VSMCs. We also observed that amlodipine and diltiazem increased MMP-1 and MMP-2 activity in human vascular endothelial cells (unpublished observation). Thus, we cannot agree with their premise that CCBs prevent atherogenesis by inducing TIMPs via IL-6 expression.

In addition, both positive and negative effects of CCBs on IL-6 expression have been reported in various kinds of cells.⁵ We investigated the effects of the . . . [Full Text of this Article]

Oliver Eickelberg, MD

Yale University, New Haven, Conn

Michael Roth, PhD; Jochen J. Rüdiger, MD; Michael Tamm, MD; André P. Perruchoud, MD

Department of Research and Internal Medicine, University Hospital, Basel, Switzerland

Lutz-Henning Block, MD

Department of Internal Medicine IV, University Hospital, Vienna, Austria

Rainer Mussmann, PhD

Division of Molecular Biology, The Netherlands Cancer Institute

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