PDGF-Induced Migration of Vascular Smooth Muscle Cells Is Inhibited by Heme Oxygenase-1 Via VEGFR2 Upregulation and Subsequent Assembly of Inactive VEGFR2/PDGFR beta Heterodimers

Caroline Cheng; Remco Haasdijk; Dennie Tempel; Wijnand den Dekker; Ihsane Chrifi; Lau Blonden; Esther Kamp; Marjan Boer; Petra Bürgisser; A Noorderloos; Joost Rens; Timo ten Hagen; Eric Duckers

doi:10.1161/ATVBAHA.112.245530

PDGF-Induced Migration of Vascular Smooth Muscle Cells Is Inhibited by Heme Oxygenase-1 Via VEGFR2 Upregulation and Subsequent Assembly of Inactive VEGFR2/PDGFR beta Heterodimers

Caroline Cheng, Remco Haasdijk, Dennie Tempel, Wijnand den Dekker, Ihsane Chrifi, Lau Blonden, Esther Kamp, Marjan Boer, Petra Bürgisser, A Noorderloos, Joost Rens, Timo ten Hagen, Eric Duckers

Research output: Contribution to journal › Article › Academic › peer-review

32 Citations (Scopus)

Abstract

Objective-In cardiovascular regulation, heme oxygenase-1 (HO-1) activity has been shown to inhibit vascular smooth muscle cell (VSMC) proliferation by promoting cell cycle arrest at the G1/S phase. However, the effect of HO-1 on VSMC migration remains unclear. We aim to elucidate the mechanism by which HO-1 regulates PDGFBB-induced VSMC migration. Methods and Results-Transduction of HO-1 cDNA adenoviral vector severely impeded human VSMC migration in a scratch, transmembrane, and directional migration assay in response to PDGFBB stimulation. Similarly, HO-1 overexpression in the remodeling process during murine retinal vasculature development attenuated VSMC coverage over the major arterial branches as compared with sham vector-transduced eyes. HO-1 expression in VSMCs significantly upregulated VEGFA and VEGFR2 expression, which subsequen Conclusion-These findings identify a potent antimigratory function of HO-1 in VSMCs, a mechanism that involves VEGFA and VEGFR2 upregulation, followed by assembly of inactive VEGFR2/PDGFR beta complexes that attenuates effective PDGFR beta signaling. (Arterioscler Thromb Vasc Biol.2012;32:1289-1298.)

Original language	Undefined/Unknown
Pages (from-to)	1289-+
Journal	Arteriosclerosis Thrombosis & Vascular Biology
Volume	32
Issue number	5
DOIs	https://doi.org/10.1161/ATVBAHA.112.245530
Publication status	Published - 2012

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EMC COEUR-09
EMC MM-03-47-11

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10.1161/ATVBAHA.112.245530

http://hdl.handle.net/1765/69693

Cite this

Cheng, C., Haasdijk, R., Tempel, D., den Dekker, W., Chrifi, I., Blonden, L., Kamp, E., Boer, M., Bürgisser, P., Noorderloos, A., Rens, J., ten Hagen, T., & Duckers, E. (2012). PDGF-Induced Migration of Vascular Smooth Muscle Cells Is Inhibited by Heme Oxygenase-1 Via VEGFR2 Upregulation and Subsequent Assembly of Inactive VEGFR2/PDGFR beta Heterodimers. Arteriosclerosis Thrombosis & Vascular Biology, 32(5), 1289-+. https://doi.org/10.1161/ATVBAHA.112.245530

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title = "PDGF-Induced Migration of Vascular Smooth Muscle Cells Is Inhibited by Heme Oxygenase-1 Via VEGFR2 Upregulation and Subsequent Assembly of Inactive VEGFR2/PDGFR beta Heterodimers",

abstract = "Objective-In cardiovascular regulation, heme oxygenase-1 (HO-1) activity has been shown to inhibit vascular smooth muscle cell (VSMC) proliferation by promoting cell cycle arrest at the G1/S phase. However, the effect of HO-1 on VSMC migration remains unclear. We aim to elucidate the mechanism by which HO-1 regulates PDGFBB-induced VSMC migration. Methods and Results-Transduction of HO-1 cDNA adenoviral vector severely impeded human VSMC migration in a scratch, transmembrane, and directional migration assay in response to PDGFBB stimulation. Similarly, HO-1 overexpression in the remodeling process during murine retinal vasculature development attenuated VSMC coverage over the major arterial branches as compared with sham vector-transduced eyes. HO-1 expression in VSMCs significantly upregulated VEGFA and VEGFR2 expression, which subsequen Conclusion-These findings identify a potent antimigratory function of HO-1 in VSMCs, a mechanism that involves VEGFA and VEGFR2 upregulation, followed by assembly of inactive VEGFR2/PDGFR beta complexes that attenuates effective PDGFR beta signaling. (Arterioscler Thromb Vasc Biol.2012;32:1289-1298.)",

author = "Caroline Cheng and Remco Haasdijk and Dennie Tempel and {den Dekker}, Wijnand and Ihsane Chrifi and Lau Blonden and Esther Kamp and Marjan Boer and Petra B{\"u}rgisser and A Noorderloos and Joost Rens and {ten Hagen}, Timo and Eric Duckers",

year = "2012",

doi = "10.1161/ATVBAHA.112.245530",

language = "Undefined/Unknown",

volume = "32",

pages = "1289--+",

journal = "Arteriosclerosis Thrombosis & Vascular Biology",

issn = "1079-5642",

publisher = "Lippincott Williams & Wilkins",

number = "5",

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Cheng, C, Haasdijk, R, Tempel, D, den Dekker, W, Chrifi, I, Blonden, L, Kamp, E, Boer, M , Bürgisser, P, Noorderloos, A, Rens, J, ten Hagen, T & Duckers, E 2012, 'PDGF-Induced Migration of Vascular Smooth Muscle Cells Is Inhibited by Heme Oxygenase-1 Via VEGFR2 Upregulation and Subsequent Assembly of Inactive VEGFR2/PDGFR beta Heterodimers', Arteriosclerosis Thrombosis & Vascular Biology, vol. 32, no. 5, pp. 1289-+. https://doi.org/10.1161/ATVBAHA.112.245530

PDGF-Induced Migration of Vascular Smooth Muscle Cells Is Inhibited by Heme Oxygenase-1 Via VEGFR2 Upregulation and Subsequent Assembly of Inactive VEGFR2/PDGFR beta Heterodimers. / Cheng, Caroline; Haasdijk, Remco; Tempel, Dennie et al.
In: Arteriosclerosis Thrombosis & Vascular Biology, Vol. 32, No. 5, 2012, p. 1289-+.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - PDGF-Induced Migration of Vascular Smooth Muscle Cells Is Inhibited by Heme Oxygenase-1 Via VEGFR2 Upregulation and Subsequent Assembly of Inactive VEGFR2/PDGFR beta Heterodimers

AU - Cheng, Caroline

AU - Haasdijk, Remco

AU - Tempel, Dennie

AU - den Dekker, Wijnand

AU - Chrifi, Ihsane

AU - Blonden, Lau

AU - Kamp, Esther

AU - Boer, Marjan

AU - Bürgisser, Petra

AU - Noorderloos, A

AU - Rens, Joost

AU - ten Hagen, Timo

AU - Duckers, Eric

PY - 2012

Y1 - 2012

N2 - Objective-In cardiovascular regulation, heme oxygenase-1 (HO-1) activity has been shown to inhibit vascular smooth muscle cell (VSMC) proliferation by promoting cell cycle arrest at the G1/S phase. However, the effect of HO-1 on VSMC migration remains unclear. We aim to elucidate the mechanism by which HO-1 regulates PDGFBB-induced VSMC migration. Methods and Results-Transduction of HO-1 cDNA adenoviral vector severely impeded human VSMC migration in a scratch, transmembrane, and directional migration assay in response to PDGFBB stimulation. Similarly, HO-1 overexpression in the remodeling process during murine retinal vasculature development attenuated VSMC coverage over the major arterial branches as compared with sham vector-transduced eyes. HO-1 expression in VSMCs significantly upregulated VEGFA and VEGFR2 expression, which subsequen Conclusion-These findings identify a potent antimigratory function of HO-1 in VSMCs, a mechanism that involves VEGFA and VEGFR2 upregulation, followed by assembly of inactive VEGFR2/PDGFR beta complexes that attenuates effective PDGFR beta signaling. (Arterioscler Thromb Vasc Biol.2012;32:1289-1298.)

AB - Objective-In cardiovascular regulation, heme oxygenase-1 (HO-1) activity has been shown to inhibit vascular smooth muscle cell (VSMC) proliferation by promoting cell cycle arrest at the G1/S phase. However, the effect of HO-1 on VSMC migration remains unclear. We aim to elucidate the mechanism by which HO-1 regulates PDGFBB-induced VSMC migration. Methods and Results-Transduction of HO-1 cDNA adenoviral vector severely impeded human VSMC migration in a scratch, transmembrane, and directional migration assay in response to PDGFBB stimulation. Similarly, HO-1 overexpression in the remodeling process during murine retinal vasculature development attenuated VSMC coverage over the major arterial branches as compared with sham vector-transduced eyes. HO-1 expression in VSMCs significantly upregulated VEGFA and VEGFR2 expression, which subsequen Conclusion-These findings identify a potent antimigratory function of HO-1 in VSMCs, a mechanism that involves VEGFA and VEGFR2 upregulation, followed by assembly of inactive VEGFR2/PDGFR beta complexes that attenuates effective PDGFR beta signaling. (Arterioscler Thromb Vasc Biol.2012;32:1289-1298.)

U2 - 10.1161/ATVBAHA.112.245530

DO - 10.1161/ATVBAHA.112.245530

M3 - Article

C2 - 22426130

SN - 1079-5642

VL - 32

SP - 1289-+

JO - Arteriosclerosis Thrombosis & Vascular Biology

JF - Arteriosclerosis Thrombosis & Vascular Biology

IS - 5

ER -