Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions: Possible pathophysiological significance of VEGF in progression of atherosclerosis

Mayumi Inoue, Hiroshi Itoh, Makiko Ueda, Takahiko Naruko, Akiko Kojima, Ryushi Komatsu, Kentaro Doi, Yoshihiro Ogawa, Naohisa Tamura, Kazuhiko Takaya, Toshio Igaki, Jun Yamashita, Tae Hwa Chun, Ken Masatsugu, Anton E. Becker, Kazuwa Nakao

Research output: Contribution to journalArticle

395 Citations (Scopus)

Abstract

Background - Vascular endothelial growth factor (VEGF) is an important angiogenic factor reported to induce migration and proliferation of endothelial cells, enhance vascular permeability, and modulate thrombogenicity. VEGF expression in cultured cells (smooth muscle cells, macrophages, endothelial cells) is controlled by growth factors and cytokines. Hence, the question arises of whether VEGF could play a role in atherogenesis. Methods and Results - Frozen sections from 38 coronary artery segments were studied. The specimens were characterized as normal with diffuse intimal thickening, early atherosclerosis with hypercellularity, and advanced atherosclerosis (atheromatous plaques, fibrous plaques, and totally occlusive lesions). VEGF expression as well as the expression of 2 VEGF receptors, flt-1 and Flk-1, were studied with immunohistochemical techniques in these samples at the different stages of human coronary atherosclerosis progression. The expression of VEGF mRNA was also studied with reverse transcription-polymerase chain reaction. Normal arterial segments showed no substantial VEGF expression hypercellular and atheromatous lesions showed distinct VEGF positivity of activated endothelial cells, macrophages, and partially differentiated smooth muscle cells. VEGF positivity was also detected in endothelial cells of intraplaque microvessels within advanced lesions. In totally occlusive lesions with extensive neovascularization, intense immunostaining for VEGF was observed in accumulated macrophages and endothelial cells of the microvessels. Furthermore, VEGF mRNA expression was detected in atherosclerotic coronary segments but not in normal coronary segments. The immunostainings for flt-1 and Flk-1 were detected in aggregating macrophages in atherosclerotic lesions and also in endothelial cells of the microvessels in totally occlusive lesions. Conclusions - These results demonstrate distinct expression of VEGF and its receptors (flt-1 and Flk-1) in atherosclerotic lesions in human coronary arteries. Considering the multipotent actions of VEGF documented experimentally in vivo and in vitro, our findings suggest that VEGF may have some role in the progression of human coronary atherosclerosis, as well as in recanalization processes in obstructive coronary diseases.

Original languageEnglish
Pages (from-to)2108-2116
Number of pages9
JournalCirculation
Volume98
Issue number20
Publication statusPublished - 1998 Nov 17
Externally publishedYes

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Vascular Endothelial Growth Factor A
Atherosclerosis
Endothelial Cells
Microvessels
Macrophages
Smooth Muscle Myocytes
Coronary Artery Disease
Coronary Vessels
Tunica Intima
Vascular Endothelial Growth Factor Receptor-1
Messenger RNA
Vascular Endothelial Growth Factor Receptor
Angiogenesis Inducing Agents
Frozen Sections
Capillary Permeability
Atherosclerotic Plaques
Reverse Transcription
Coronary Disease
Cultured Cells
Intercellular Signaling Peptides and Proteins

Keywords

  • Angiogenesis
  • Atherosclerosis
  • Coronary disease
  • Immunohistochemistry
  • Pathology

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions : Possible pathophysiological significance of VEGF in progression of atherosclerosis. / Inoue, Mayumi; Itoh, Hiroshi; Ueda, Makiko; Naruko, Takahiko; Kojima, Akiko; Komatsu, Ryushi; Doi, Kentaro; Ogawa, Yoshihiro; Tamura, Naohisa; Takaya, Kazuhiko; Igaki, Toshio; Yamashita, Jun; Chun, Tae Hwa; Masatsugu, Ken; Becker, Anton E.; Nakao, Kazuwa.

In: Circulation, Vol. 98, No. 20, 17.11.1998, p. 2108-2116.

Research output: Contribution to journalArticle

Inoue, M, Itoh, H, Ueda, M, Naruko, T, Kojima, A, Komatsu, R, Doi, K, Ogawa, Y, Tamura, N, Takaya, K, Igaki, T, Yamashita, J, Chun, TH, Masatsugu, K, Becker, AE & Nakao, K 1998, 'Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions: Possible pathophysiological significance of VEGF in progression of atherosclerosis', Circulation, vol. 98, no. 20, pp. 2108-2116.
Inoue, Mayumi ; Itoh, Hiroshi ; Ueda, Makiko ; Naruko, Takahiko ; Kojima, Akiko ; Komatsu, Ryushi ; Doi, Kentaro ; Ogawa, Yoshihiro ; Tamura, Naohisa ; Takaya, Kazuhiko ; Igaki, Toshio ; Yamashita, Jun ; Chun, Tae Hwa ; Masatsugu, Ken ; Becker, Anton E. ; Nakao, Kazuwa. / Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions : Possible pathophysiological significance of VEGF in progression of atherosclerosis. In: Circulation. 1998 ; Vol. 98, No. 20. pp. 2108-2116.
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abstract = "Background - Vascular endothelial growth factor (VEGF) is an important angiogenic factor reported to induce migration and proliferation of endothelial cells, enhance vascular permeability, and modulate thrombogenicity. VEGF expression in cultured cells (smooth muscle cells, macrophages, endothelial cells) is controlled by growth factors and cytokines. Hence, the question arises of whether VEGF could play a role in atherogenesis. Methods and Results - Frozen sections from 38 coronary artery segments were studied. The specimens were characterized as normal with diffuse intimal thickening, early atherosclerosis with hypercellularity, and advanced atherosclerosis (atheromatous plaques, fibrous plaques, and totally occlusive lesions). VEGF expression as well as the expression of 2 VEGF receptors, flt-1 and Flk-1, were studied with immunohistochemical techniques in these samples at the different stages of human coronary atherosclerosis progression. The expression of VEGF mRNA was also studied with reverse transcription-polymerase chain reaction. Normal arterial segments showed no substantial VEGF expression hypercellular and atheromatous lesions showed distinct VEGF positivity of activated endothelial cells, macrophages, and partially differentiated smooth muscle cells. VEGF positivity was also detected in endothelial cells of intraplaque microvessels within advanced lesions. In totally occlusive lesions with extensive neovascularization, intense immunostaining for VEGF was observed in accumulated macrophages and endothelial cells of the microvessels. Furthermore, VEGF mRNA expression was detected in atherosclerotic coronary segments but not in normal coronary segments. The immunostainings for flt-1 and Flk-1 were detected in aggregating macrophages in atherosclerotic lesions and also in endothelial cells of the microvessels in totally occlusive lesions. Conclusions - These results demonstrate distinct expression of VEGF and its receptors (flt-1 and Flk-1) in atherosclerotic lesions in human coronary arteries. Considering the multipotent actions of VEGF documented experimentally in vivo and in vitro, our findings suggest that VEGF may have some role in the progression of human coronary atherosclerosis, as well as in recanalization processes in obstructive coronary diseases.",
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T1 - Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions

T2 - Possible pathophysiological significance of VEGF in progression of atherosclerosis

AU - Inoue, Mayumi

AU - Itoh, Hiroshi

AU - Ueda, Makiko

AU - Naruko, Takahiko

AU - Kojima, Akiko

AU - Komatsu, Ryushi

AU - Doi, Kentaro

AU - Ogawa, Yoshihiro

AU - Tamura, Naohisa

AU - Takaya, Kazuhiko

AU - Igaki, Toshio

AU - Yamashita, Jun

AU - Chun, Tae Hwa

AU - Masatsugu, Ken

AU - Becker, Anton E.

AU - Nakao, Kazuwa

PY - 1998/11/17

Y1 - 1998/11/17

N2 - Background - Vascular endothelial growth factor (VEGF) is an important angiogenic factor reported to induce migration and proliferation of endothelial cells, enhance vascular permeability, and modulate thrombogenicity. VEGF expression in cultured cells (smooth muscle cells, macrophages, endothelial cells) is controlled by growth factors and cytokines. Hence, the question arises of whether VEGF could play a role in atherogenesis. Methods and Results - Frozen sections from 38 coronary artery segments were studied. The specimens were characterized as normal with diffuse intimal thickening, early atherosclerosis with hypercellularity, and advanced atherosclerosis (atheromatous plaques, fibrous plaques, and totally occlusive lesions). VEGF expression as well as the expression of 2 VEGF receptors, flt-1 and Flk-1, were studied with immunohistochemical techniques in these samples at the different stages of human coronary atherosclerosis progression. The expression of VEGF mRNA was also studied with reverse transcription-polymerase chain reaction. Normal arterial segments showed no substantial VEGF expression hypercellular and atheromatous lesions showed distinct VEGF positivity of activated endothelial cells, macrophages, and partially differentiated smooth muscle cells. VEGF positivity was also detected in endothelial cells of intraplaque microvessels within advanced lesions. In totally occlusive lesions with extensive neovascularization, intense immunostaining for VEGF was observed in accumulated macrophages and endothelial cells of the microvessels. Furthermore, VEGF mRNA expression was detected in atherosclerotic coronary segments but not in normal coronary segments. The immunostainings for flt-1 and Flk-1 were detected in aggregating macrophages in atherosclerotic lesions and also in endothelial cells of the microvessels in totally occlusive lesions. Conclusions - These results demonstrate distinct expression of VEGF and its receptors (flt-1 and Flk-1) in atherosclerotic lesions in human coronary arteries. Considering the multipotent actions of VEGF documented experimentally in vivo and in vitro, our findings suggest that VEGF may have some role in the progression of human coronary atherosclerosis, as well as in recanalization processes in obstructive coronary diseases.

AB - Background - Vascular endothelial growth factor (VEGF) is an important angiogenic factor reported to induce migration and proliferation of endothelial cells, enhance vascular permeability, and modulate thrombogenicity. VEGF expression in cultured cells (smooth muscle cells, macrophages, endothelial cells) is controlled by growth factors and cytokines. Hence, the question arises of whether VEGF could play a role in atherogenesis. Methods and Results - Frozen sections from 38 coronary artery segments were studied. The specimens were characterized as normal with diffuse intimal thickening, early atherosclerosis with hypercellularity, and advanced atherosclerosis (atheromatous plaques, fibrous plaques, and totally occlusive lesions). VEGF expression as well as the expression of 2 VEGF receptors, flt-1 and Flk-1, were studied with immunohistochemical techniques in these samples at the different stages of human coronary atherosclerosis progression. The expression of VEGF mRNA was also studied with reverse transcription-polymerase chain reaction. Normal arterial segments showed no substantial VEGF expression hypercellular and atheromatous lesions showed distinct VEGF positivity of activated endothelial cells, macrophages, and partially differentiated smooth muscle cells. VEGF positivity was also detected in endothelial cells of intraplaque microvessels within advanced lesions. In totally occlusive lesions with extensive neovascularization, intense immunostaining for VEGF was observed in accumulated macrophages and endothelial cells of the microvessels. Furthermore, VEGF mRNA expression was detected in atherosclerotic coronary segments but not in normal coronary segments. The immunostainings for flt-1 and Flk-1 were detected in aggregating macrophages in atherosclerotic lesions and also in endothelial cells of the microvessels in totally occlusive lesions. Conclusions - These results demonstrate distinct expression of VEGF and its receptors (flt-1 and Flk-1) in atherosclerotic lesions in human coronary arteries. Considering the multipotent actions of VEGF documented experimentally in vivo and in vitro, our findings suggest that VEGF may have some role in the progression of human coronary atherosclerosis, as well as in recanalization processes in obstructive coronary diseases.

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KW - Atherosclerosis

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