Adenovirus-mediated transfer of a dominant-negative H-ras suppresses neointimal formation in balloon-injured arteries in vivo

Hikaru Ueno, Hiroaki Yamamoto, Shinichi Ito, Jian Jun Li, Akira Takeshita

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Abnormal migration and proliferation of arterial smooth muscle cells may be a central event in inflammatory proliferative arterial diseases such as atherosclerosis and restenosis after angioplasty. The proto-oncogene c-H-ras is considered to be a key transducer in various growth-signaling events. We constructed an adenoviral vector (AdexCAHRasY57) expressing a potent dominant-negative mutated form of c-H-ras in which tyrosine replaces aspartic acid at residue 57. Infection of smooth muscle cells with AdexCAHRasY57 produced a large quantity of H-ras-p21, completely inhibited serum-stimulated activation of mitogen-activated protein kinase, and abolished the DNA synthesis in response to serum mitogens. However, a surge of intracellular Ca2+ concentration in response to platelet-derived growth factor was not affected, suggesting that some cellular functions were preserved. When we applied AdexCAHRasY57 into balloon-injured rat carotid arteries from inside the lumen, neointimal formation was significantly reduced (neointima/media ratio: 0.28) compared with that (1.50) in arteries treated with either injury alone or injury and infection with a control adenovirus, AdexCALacZ, expressing bacterial β-galactosidase. Our results suggest that adenovirus- mediated arterial transfer of dominant-negative H-ras may be a practical form of effective molecular intervention for proliferative arterial diseases.

Original languageEnglish
Pages (from-to)898-904
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume17
Issue number5
DOIs
Publication statusPublished - Jan 1 1997

Fingerprint

Adenoviridae
Smooth Muscle Myocytes
Arteries
Galactosidases
Proto-Oncogene Proteins p21(ras)
Neointima
ras Genes
Platelet-Derived Growth Factor
Wounds and Injuries
Infection
Mitogen-Activated Protein Kinases
Transducers
Serum
Mitogens
Angioplasty
Carotid Arteries
Aspartic Acid
Tyrosine
Atherosclerosis
DNA

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Adenovirus-mediated transfer of a dominant-negative H-ras suppresses neointimal formation in balloon-injured arteries in vivo. / Ueno, Hikaru; Yamamoto, Hiroaki; Ito, Shinichi; Li, Jian Jun; Takeshita, Akira.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 17, No. 5, 01.01.1997, p. 898-904.

Research output: Contribution to journalArticle

@article{f53a7a68c4124391a7c961744aae360b,
title = "Adenovirus-mediated transfer of a dominant-negative H-ras suppresses neointimal formation in balloon-injured arteries in vivo",
abstract = "Abnormal migration and proliferation of arterial smooth muscle cells may be a central event in inflammatory proliferative arterial diseases such as atherosclerosis and restenosis after angioplasty. The proto-oncogene c-H-ras is considered to be a key transducer in various growth-signaling events. We constructed an adenoviral vector (AdexCAHRasY57) expressing a potent dominant-negative mutated form of c-H-ras in which tyrosine replaces aspartic acid at residue 57. Infection of smooth muscle cells with AdexCAHRasY57 produced a large quantity of H-ras-p21, completely inhibited serum-stimulated activation of mitogen-activated protein kinase, and abolished the DNA synthesis in response to serum mitogens. However, a surge of intracellular Ca2+ concentration in response to platelet-derived growth factor was not affected, suggesting that some cellular functions were preserved. When we applied AdexCAHRasY57 into balloon-injured rat carotid arteries from inside the lumen, neointimal formation was significantly reduced (neointima/media ratio: 0.28) compared with that (1.50) in arteries treated with either injury alone or injury and infection with a control adenovirus, AdexCALacZ, expressing bacterial β-galactosidase. Our results suggest that adenovirus- mediated arterial transfer of dominant-negative H-ras may be a practical form of effective molecular intervention for proliferative arterial diseases.",
author = "Hikaru Ueno and Hiroaki Yamamoto and Shinichi Ito and Li, {Jian Jun} and Akira Takeshita",
year = "1997",
month = "1",
day = "1",
doi = "10.1161/01.ATV.17.5.898",
language = "English",
volume = "17",
pages = "898--904",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Adenovirus-mediated transfer of a dominant-negative H-ras suppresses neointimal formation in balloon-injured arteries in vivo

AU - Ueno, Hikaru

AU - Yamamoto, Hiroaki

AU - Ito, Shinichi

AU - Li, Jian Jun

AU - Takeshita, Akira

PY - 1997/1/1

Y1 - 1997/1/1

N2 - Abnormal migration and proliferation of arterial smooth muscle cells may be a central event in inflammatory proliferative arterial diseases such as atherosclerosis and restenosis after angioplasty. The proto-oncogene c-H-ras is considered to be a key transducer in various growth-signaling events. We constructed an adenoviral vector (AdexCAHRasY57) expressing a potent dominant-negative mutated form of c-H-ras in which tyrosine replaces aspartic acid at residue 57. Infection of smooth muscle cells with AdexCAHRasY57 produced a large quantity of H-ras-p21, completely inhibited serum-stimulated activation of mitogen-activated protein kinase, and abolished the DNA synthesis in response to serum mitogens. However, a surge of intracellular Ca2+ concentration in response to platelet-derived growth factor was not affected, suggesting that some cellular functions were preserved. When we applied AdexCAHRasY57 into balloon-injured rat carotid arteries from inside the lumen, neointimal formation was significantly reduced (neointima/media ratio: 0.28) compared with that (1.50) in arteries treated with either injury alone or injury and infection with a control adenovirus, AdexCALacZ, expressing bacterial β-galactosidase. Our results suggest that adenovirus- mediated arterial transfer of dominant-negative H-ras may be a practical form of effective molecular intervention for proliferative arterial diseases.

AB - Abnormal migration and proliferation of arterial smooth muscle cells may be a central event in inflammatory proliferative arterial diseases such as atherosclerosis and restenosis after angioplasty. The proto-oncogene c-H-ras is considered to be a key transducer in various growth-signaling events. We constructed an adenoviral vector (AdexCAHRasY57) expressing a potent dominant-negative mutated form of c-H-ras in which tyrosine replaces aspartic acid at residue 57. Infection of smooth muscle cells with AdexCAHRasY57 produced a large quantity of H-ras-p21, completely inhibited serum-stimulated activation of mitogen-activated protein kinase, and abolished the DNA synthesis in response to serum mitogens. However, a surge of intracellular Ca2+ concentration in response to platelet-derived growth factor was not affected, suggesting that some cellular functions were preserved. When we applied AdexCAHRasY57 into balloon-injured rat carotid arteries from inside the lumen, neointimal formation was significantly reduced (neointima/media ratio: 0.28) compared with that (1.50) in arteries treated with either injury alone or injury and infection with a control adenovirus, AdexCALacZ, expressing bacterial β-galactosidase. Our results suggest that adenovirus- mediated arterial transfer of dominant-negative H-ras may be a practical form of effective molecular intervention for proliferative arterial diseases.

UR - http://www.scopus.com/inward/record.url?scp=0031005738&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031005738&partnerID=8YFLogxK

U2 - 10.1161/01.ATV.17.5.898

DO - 10.1161/01.ATV.17.5.898

M3 - Article

VL - 17

SP - 898

EP - 904

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 5

ER -