Matrix metalloproteinase-9 (92-kd gelatinase/type IV collagenase equals gelatinase B) can degrade arterial elastin

Shogo Katsuda, Yasunori Okada, Yoshikatsu Okada, Kazushi Imai, Isao Nakanishi

研究成果: Article査読

78 被引用数 (Scopus)

抄録

Degradation of elastic fibers in the arterial walls is an important step in the development of atherosclerosis. To identify the enzyme(s) responsible for the elastinolysis, we have designed an ex vivo model of aortic explants cultured with or without THP-1 cells (human monocyte/macrophage-like cells). After culturing with THP-1 cells for 5 days, elastic fibers of the aortic explants were fragmented and lost. With insoluble [3H] elastin as a substrate, elastin-degrading activity could be detected in the culture medium. Zymography in sodium dodecyl sulfate-polyacrylamide gel electrophoresis containing α-elastin showed the presence of elastinolytic activity with 92 kd in the medium from the aortic tissue with THP-1 cell cultures, whereas the medium from the aortic tissue without THP-1 cells contained negligible elastinolytic activity. The activity was inhibited by ethylenediamine tetraacetic acid but not by phenylmethane sulfonyl fluoride, N-ethylmaleimide, or pepstatin A, indicating that the enzyme belongs to a class of metalloproteinases. In addition, destruction of the elastic fibers of the aortic explants cultured with THP-1 cells was completely inhibited only by metalloproteinase inhibitors. Immunoblot analyses demonstrated that the proteinase responsible for the elastinolytic activity is matrix metalloproteinase-9 (92-kd gelatinase/type IV collagenase = gelatinase B). Using immunocytochemistry, the metalloproteinase was localized in the THP-1 cells but not in the medial smooth muscle cells. These results suggest that matrix metalloproteinase-9 produced by THP-1 cells is of importance to degradation of elastic fibers in the aortic explants. The role of macrophages in the atherosclerosis is discussed with reference to elastinolysis of the arterial walls.

本文言語English
ページ(範囲)1208-1218
ページ数11
ジャーナルAmerican Journal of Pathology
145
5
出版ステータスPublished - 1994 11月
外部発表はい

ASJC Scopus subject areas

  • 病理学および法医学

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