Abstract
We reported that carbon monoxide (CO) generated through heme oxygenase (HO) inhibits mitogen-induced proliferation of vascular smooth muscle cells (VSMCs). We report that balloon injury induces HO-1, the stress-inducible isozyme of HO, in VSMCs and inhibits neointimal formation through the action of endogenous CO. Northern blot analysis and immunohistochemistry revealed that HO-1 is markedly induced in the media as early as 1 day after injury, whereas only a little expression was detected in the intact carotid artery. The neointimal proliferative changes were augmented or inhibited by the HO inhibitors or inducer, respectively, and effects of these interventions were not altered by suppression of endogenous nitric oxide (NO), if any. To elucidate the mechanisms by which HO controls the proliferative changes, effects of alterations in the HO reaction were examined by determining angiotensin II-elicited VSMC proliferation in vitro: the HO inducer attenuated and its inhibitor restored the proliferative response to angiotensin II (1 nM and 100 nM). Hemoglobin, a reagent trapping both NO and CO, but not methemoglobin, which can capture NO but not CO, augmented the proliferative response. These data suggest that endogenous CO serves as a protective factor that limits the excessive VSMC proliferation associated with vascular diseases.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 278 |
| Issue number | 2 47-2 |
| Publication status | Published - 2000 Feb |
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Keywords
- Atherosclerosis
- Balloon injury
- Heme oxygenase
- Proliferation
- Vascular smooth muscle cell
ASJC Scopus subject areas
- Physiology
- Physiology (medical)
Cite this
Protective roles of endogenous carbon monoxide in neointimal development elicited by arterial injury. / Togane, Yuko; Morita, Toshisuke; Suematsu, Makoto; Ishimura, Yuzuru; Yamazaki, Jun Ichi; Katayama, Shigehiro.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 278, No. 2 47-2, 02.2000.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Protective roles of endogenous carbon monoxide in neointimal development elicited by arterial injury
AU - Togane, Yuko
AU - Morita, Toshisuke
AU - Suematsu, Makoto
AU - Ishimura, Yuzuru
AU - Yamazaki, Jun Ichi
AU - Katayama, Shigehiro
PY - 2000/2
Y1 - 2000/2
N2 - We reported that carbon monoxide (CO) generated through heme oxygenase (HO) inhibits mitogen-induced proliferation of vascular smooth muscle cells (VSMCs). We report that balloon injury induces HO-1, the stress-inducible isozyme of HO, in VSMCs and inhibits neointimal formation through the action of endogenous CO. Northern blot analysis and immunohistochemistry revealed that HO-1 is markedly induced in the media as early as 1 day after injury, whereas only a little expression was detected in the intact carotid artery. The neointimal proliferative changes were augmented or inhibited by the HO inhibitors or inducer, respectively, and effects of these interventions were not altered by suppression of endogenous nitric oxide (NO), if any. To elucidate the mechanisms by which HO controls the proliferative changes, effects of alterations in the HO reaction were examined by determining angiotensin II-elicited VSMC proliferation in vitro: the HO inducer attenuated and its inhibitor restored the proliferative response to angiotensin II (1 nM and 100 nM). Hemoglobin, a reagent trapping both NO and CO, but not methemoglobin, which can capture NO but not CO, augmented the proliferative response. These data suggest that endogenous CO serves as a protective factor that limits the excessive VSMC proliferation associated with vascular diseases.
AB - We reported that carbon monoxide (CO) generated through heme oxygenase (HO) inhibits mitogen-induced proliferation of vascular smooth muscle cells (VSMCs). We report that balloon injury induces HO-1, the stress-inducible isozyme of HO, in VSMCs and inhibits neointimal formation through the action of endogenous CO. Northern blot analysis and immunohistochemistry revealed that HO-1 is markedly induced in the media as early as 1 day after injury, whereas only a little expression was detected in the intact carotid artery. The neointimal proliferative changes were augmented or inhibited by the HO inhibitors or inducer, respectively, and effects of these interventions were not altered by suppression of endogenous nitric oxide (NO), if any. To elucidate the mechanisms by which HO controls the proliferative changes, effects of alterations in the HO reaction were examined by determining angiotensin II-elicited VSMC proliferation in vitro: the HO inducer attenuated and its inhibitor restored the proliferative response to angiotensin II (1 nM and 100 nM). Hemoglobin, a reagent trapping both NO and CO, but not methemoglobin, which can capture NO but not CO, augmented the proliferative response. These data suggest that endogenous CO serves as a protective factor that limits the excessive VSMC proliferation associated with vascular diseases.
KW - Atherosclerosis
KW - Balloon injury
KW - Heme oxygenase
KW - Proliferation
KW - Vascular smooth muscle cell
UR - http://www.scopus.com/inward/record.url?scp=0034063826&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034063826&partnerID=8YFLogxK
M3 - Article
C2 - 10666095
AN - SCOPUS:0034063826
VL - 278
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 2 47-2
ER -