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(Circulation. 2000;101:e239-a.)
© 2000 American Heart Association, Inc.

Circulation Electronic Pages

The Significance of Expression of Proliferating Cell Nuclear Antigen in the Cardiovascular System: Mitosis or DNA Repair?

Laszlo Hegyi, MD, PhD

Department of Medicine

Jeremy N. Skepper, PhD

Multi-Imaging Centre Department of Anatomy, University of Cambridge, Cambridge, United Kingdom

	Introduction

 
To the Editor:

We read the article by Kanoh et al¹ with great interest. They showed that the terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate–biotin nick-end labeling (TUNEL) technique is not specific for apoptosis, which was pointed out previously.^{2 3} Although not specific, TUNEL is a selective method³ and, within the limits imposed by its high sensitivity, the TUNEL technique stains apoptotic nuclei.^{2 3}

Kanoh et al found that a number of TUNEL-positive nuclei expressed proliferating cell nuclear antigen (PCNA) in myocytes from hearts with dilated cardiomyopathy.¹ A few years ago, we found that TUNEL-positive nuclei can express PCNA at the edge of the lipid core of human advanced atherosclerotic lesions.² This region, the periphery of the acellular core of atheroma, is chiefly occupied by lipid-laden macrophage foam cells.² We have come to the same conclusion as Kanoh et al: the coexpression of PCNA and TUNEL (PCNA being the accessory protein of DNA polymerase ⁴ ) indicates DNA repair synthesis. We also suggested that this repair may presage apoptosis in human atherosclerotic lesions.² Indeed, the presence of TUNEL-positive PCNA-negative nuclei (or nuclear fragments) in the lesions² may suggest late stages of apoptosis.

These observations underline the most likely possibility: the expression of PCNA and certain other markers of DNA synthesis, which are frequently used to estimate the fraction of proliferative cells, may also show DNA repair synthesis.^{1 2 5} The positivity of nick-end labeling techniques, including TUNEL, proves extensive DNA damage and large numbers of DNA breaks exist in these nuclei.

Taken together, the expression of PCNA . . . [Full Text of this Article]

Motoo Kanoh Genzou Takemura; Jun Misao; Yukihiro Hayakawa; Takuma Aoyama; Kazuhiko Nishigaki; Toshiyuki Noda; Shinya Minatoguchi; Hisayoshi Fujiwara

Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan

Kazunori Fukuda

Department of Oriental Medicine Gifu University School of Medicine

Takako Fujiwara

Department of Food Science Kyoto Women’s University, Kyoto, Japan