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(Circulation. 1996;94:1118-1124.)
© 1996 American Heart Association, Inc.

Articles

Nonmuscle and Smooth Muscle Myosin Heavy Chain Expression in Rejected Cardiac Allografts

A Study in Rat and Monkey Models

Jun-ichi Suzuki, MD; Mitsuaki Isobe, MD; Masanori Aikawa, MD; Motohiro Kawauchi, MD; Ichiro Shiojima, MD; Naoto Kobayashi, MD; Akihiro Tojo, MD; Toru Suzuki, MD; Kenjiro Kimura, MD; Toshio Nishikawa, MD; Tatsuo Sakai, MD; Morie Sekiguchi, MD; Yoshio Yazaki, MD; Ryozo Nagai, MD

the Third Department of Internal Medicine (J.S., M.A., I.S., T.S., Y.Y., R.N.), the Second Department of Internal Medicine (A.T., K.K.), and the Department of Thoracic Surgery (M.K.), Faculty of Medicine, University of Tokyo; the First Department of Internal Medicine (J.S., M.I., M.S.), Shinshu University School of Medicine, Matsumoto; the First Department of Anatomy (N.K., T.S.), Juntendo University School of Medicine, Tokyo; and the Second Department of Pathology (T.N.), Tokyo Women's Medical College, Japan.

Correspondence to Ryozo Nagai, MD, the Second Department of Internal Medicine, Gunma University, 3-39-22 Showa-cho, Maebashi, Gunma 371, Japan. E-mail nagai@news.sb.gunma-u.ac.jp.

Background Diagnosis of acute rejection and graft arteriosclerosis (chronic rejection) is critical to the success of cardiac transplantation, but accurate diagnosis is often difficult. We have reported that there are three types of vascular myosin heavy chain (MHC) isoforms: SM1, SM2, and SMemb. SM2 is specifically expressed in differentiated smooth muscle cells (SMCs). SMemb is a nonmuscle-type MHC abundantly expressed in SMCs of fetal aorta.

Methods and Results To evaluate the usefulness of MHC expression for diagnosis and analysis of acute and chronic rejection, heterotopic cardiac transplantation was performed in rats and monkeys. Immunohistochemistry, electron microscopy, and Northern blot assay were performed to evaluate MHC expression. SMemb was expressed in spindle-shaped cells located in acutely rejected myocardium in the rats and monkeys. These cells were also observed in areas lacking cellular infiltration. These SMemb-positive cells were activated fibroblasts or myofibroblasts. SMemb mRNA was enhanced parallel to the progression of acute rejection. In the coronary arteries of chronically rejected allografts, enhanced SMemb and reduced SM2 expression was observed in both thickened intima and media. The reduced medial SM2 expression was observed before the intimal thickening occurred. These cells were phenotypically modulated SMCs.

Conclusions Altered expression of MHC isoforms is a sensitive indicator in the diagnosis of acute and chronic cardiac rejection. The pathophysiology of this alteration in MHC isoform expression should be studied further to elucidate the pathogenesis of cardiac rejection.

Key Words: myosin • rejection • transplantation • monkeys

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