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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2083.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Inflammatory Response to Acute Myocardial Infarction Augments Neointimal Hyperplasia After Vascular Injury in a Remote Artery

Minoru Takaoka; Shiro Uemura; Hiroyuki Kawata; Kei-ichi Imagawa; Yukiji Takeda; Kimihiko Nakatani; Noriyuki Naya; Manabu Horii; Shigeru Yamano; Yoshihiro Miyamoto; Yasunao Yoshimasa; Yoshihiko Saito

From the First Department of Internal Medicine (M.T., S.U., H.K., K.I., Y.T., K.N., N.N., M.H., S.Y.,Y.S.), Nara Medical University, Nara, Japan; National Cardiovascular Center (Y.M., Y.Y.), Suita, Osaka, Japan.

Correspondence to Yoshihiko Saito, First Department of Internal Medicine, Nara Medical University, 84 Shijo-cho, Kashihara, Nara 634-8522, Japan. E-mail yssaito{at}naramed-u.ac.jp

Objective— Percutaneous coronary intervention (PCI) is currently the most widely accepted treatment for acute myocardial infarction (AMI). It remains unclear, however, whether post-AMI conditions might exacerbate neointimal hyperplasia and restenosis following PCI. Given that both a medial smooth muscle cell lineage and a bone marrow (BM)-derived hematopoietic stem cell lineage are now thought to contribute to neointima formation, the primary aims of the present study were to determine whether AMI augments neointimal hyperplasia at sites of arterial injury, and whether BM-derived cells contribute to that process.

Methods and Results— We simultaneously generated models of AMI and arterial injury in the same mice, some of which had received BM transplantation. We found that AMI augments neointimal hyperplasia at sites of femoral artery injury by &35% (P<0.05), but that while BM-derived cells contributed to neointimal hyperplasia, they did not contribute to the AMI-related augmentation. Expression of interleukin (IL)-6 mRNA was &7-fold higher in the neointimas of mice subjected to both AMI and arterial injury than in those of mice subjected to arterial injury alone. In addition, we observed increased synthesis of tumor necrosis factor (TNF)- within infarcted hearts and TNF- receptor type 1 (TNFR1) within injured arteries. Chronic treatment with pentoxifylline, which mainly inhibits TNF- synthesis, reduced levels of circulating TNF- and attenuated neointimal hyperplasia after AMI.

Conclusions— Conditions after AMI could exacerbate postangioplasty restenosis, not by increasing mobilization of BM-derived cells, but by stimulating signaling via TNF-, TNFR1 and IL-6.

To elucidate whether AMI exacerbate neointimal hyperplasia and restenosis after PCI, we simultaneously generated experimental models of AMI and femoral artery injury in the same mice. We demonstrate that AMI itself augments neointimal hyperplasia after vascular injury by stimulating signaling via TNF-, TNFR1, and IL-6.

Key Words: bone marrow • inflammation • myocardial infarction • restenosis • smooth muscle cell

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