CLINICAL STUDIES
Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction
Hirofumi Soejima, MD*,
Hisao Ogawa, MD*,
Hirofumi Yasue, MD*,
Koichi Kaikita, MD*,
Keiji Takazoe, MD*,
Koichi Nishiyama, MD*,
Kenji Misumi, MD*,
Shinzo Miyamoto, MD*,
Michihiro Yoshimura, MD*,
Kiyotaka Kugiyama, MD*,
Shin Nakamura, MD and
Ichiro Tsuji, PhD
* Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Kumamoto, Japan
Department of Molecular and Cellular Biology, Primate Research Institute, Kyoto University, Inuyama, Aichi, Japan
Chemo-Sero Therapeutic Research Institute, Kumamoto, Japan
Manuscript received January 4, 1999;
revised manuscript received April 22, 1999,
accepted June 11, 1999.
Reprint requests and correspondence: Dr. Hisao Ogawa, Department of Cardiovascular Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto City, 860-8556 Japan
ogawah{at}gpo.kumamoto-u.ac.jp
OBJECTIVES
We investigated the effects of enalapril therapy on plasma tissue factor (TF), tissue factor pathway inhibitor (TFPI) and monocyte chemoattractant protein-1 (MCP-1) levels in patients with acute myocardial infarction.
BACKGROUND
Macrophages express TF in human coronary atherosclerotic plaques. Both TF and TFPI are major regulators of coagulation and thrombosis. Monocyte chemoattractant protein-1 is a monocyte and macrophage chemotactic and activating factor.
METHODS
In a randomized, double-blind, placebo-controlled study beginning about two weeks after myocardial infarction, 16 patients received four weeks of placebo (placebo group) and another 16 patients received four weeks of enalapril 5 mg daily therapy (enalapril group). We performed blood sampling after administration of the doses.
RESULTS
There were no significant differences in the serum angiotensin-converting enzyme (ACE) activity, plasma TF, free TFPI or MCP-1 levels before administration between the enalapril and placebo groups. In the enalapril group, ACE activity (IU/liter) (14.0 before, 5.2 on day 3, 5.8 on day 7, 6.3 on day 28), TF levels (pg/ml) (223, 203, 182, 178) and MCP-1 levels (pg/ml) (919, 789, 790, 803) significantly decreased by day 28. However, the free TFPI levels (ng/ml) (28.2, 26.5, 26.8, 28.4) did not change. These four variables were unchanged during the study period in the placebo group.
CONCLUSIONS
This study demonstrated that administration of enalapril reduces the increased procoagulant activity in patients with myocardial infarction associated with inhibition of the activation and accumulation of macrophages and monocytes.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | ECG | = electrocardiogram | | HDL | = high-density lipoprotein | | MCP-1 | = monocyte chemoattractant protein-1 | | TF | = tissue factor | | TFPI | = tissue factor pathway inhibitor |
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