Induction of angiogenesis by smooth muscle cell‐derived factor: Possible role in neovascularization in atherosclerotic plaque

Journal of Cellular Physiology - Tập 164 Số 3 - Trang 658-667 - 1995
Masafumi Kuzuya1, Shosuke Satake1, Teiji Esaki1, Kazuyoshi Yamada1, Toshio Hayashi1, Michitaka Naito1, Kanichi Asai1, Akihisa Iguchi1
1Department of Geriatrics, Nagoya University School of Medicine, Nagoya 466, Japan

Tóm tắt

AbstractThe development of atherosclerotic plaque is associated with neovascularization in the thickened intima and media of vascular walls. Neovascularization may have a role in the progression of atherosclerotic plaque as well as in the development of intraplaque hemorrhage. However, the mechanism and stimulus for neovascularization in atherosclerotic plaque are unknown. We postulated that smooth muscle cells (SMCs), a major cellular component in the vascular wall, might contribute to the induction of neovascularization in atherosclerotic plaque through the secretion of an angiogenic factor. We observed that endothelial cells (ECs) cultured on collagen gel with SMC‐conditioned medium became spindle shaped, invaded the underlying collagen gel, and organized a capillary‐like branching cord structure in the collagen gel. The conditioned medium also stimulated EC proliferation and increased the EC‐associated plasminogen activator activity. The angiogenic factor in SMC‐conditioned medium was retained in a heparin‐Sepharose column and eluted with 0.9 M NaCl. Neutralizing anti‐vascullar endothelial growth factor (VEGF) antibody attenuated the angiogenic activity in the conditioned medium, including the induction of morphologic changes in ECs, mitogenic activity, and increased plasminogen activator activity associated with ECs. Immunoblotting analysis confirmed the secretion of VEGF from SMCs. These observations indicate that SMC may be responsible for the neovascularization in atherosclerotic plaque through the secretion of VEGF. © 1995 Wiley‐Liss, Inc.

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Journal of Cellular Physiology

Tập 164 Số 3

658-667

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