Abstract
The therapeutic use of angiogenic factors shows promise in the treatment of critical limb ischemia; however, its potential for myonephropathic metabolic syndrome (MNMS), a fatal complication caused by arterial reconstruction, has not been elucidated. The objective of this study was to evaluate the effectiveness of recombinant Sendai virus-mediated gene transfer of fibroblast growth factor-2 (FGF-2) directly compared with that of a radical scavenger, MCI-186, in a rat model of MNMS. MNMS was surgically induced by aortic occlusion below renal arteries for 4 h, followed by 6 h of reperfusion. Administration of MCI-186 (twice; iv 5 min before induced ischemia and ip 5 min before reperfusion; 10 mg/kg, respectively), but not FGF-2 gene transfer (once, 48 h before induced ischemia), dramatically prevented the increase of serum biochemical markers as well as the edema of the gastrocnemius muscle. The effect of MCI-186 was accompanied by the marked suppression of the neutrophilic infiltration into the local (muscle) and remote (lung) organs. Although serum and muscular levels of a neutrophil-chemoattractant (growth-related oncogene/cytokine-induced neutrophil chemoattractant-1) were not affected by any treatment, the serum level of soluble intercellular adhesion molecule-1 was decreased by treatment with MCI-186 but not by treatment with FGF-2. These results suggest the distinct mechanism of MNMS from critical limb ischemia without reperfusion. Therefore, radical scavenging should be paid more attention than therapeutic angiogenesis when arterial circulation is reconstructed.
| Original language | English |
|---|---|
| Pages (from-to) | H1484-H1492 |
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 290 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2006 |
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All Science Journal Classification (ASJC) codes
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
Cite this
A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia. / Kaneko, Kazuhiro; Yonemitsu, Yoshikazu; Fujii, Takaaki; Onimaru, Mitsuho; Jin, Chen Hao; Inoue, Makoto; Hasegawa, Mamoru; Onohara, Toshihiro; Maehara, Yoshihiko; Sueishi, Katsuo.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 290, No. 4, 01.04.2006, p. H1484-H1492.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia
AU - Kaneko, Kazuhiro
AU - Yonemitsu, Yoshikazu
AU - Fujii, Takaaki
AU - Onimaru, Mitsuho
AU - Jin, Chen Hao
AU - Inoue, Makoto
AU - Hasegawa, Mamoru
AU - Onohara, Toshihiro
AU - Maehara, Yoshihiko
AU - Sueishi, Katsuo
PY - 2006/4/1
Y1 - 2006/4/1
N2 - The therapeutic use of angiogenic factors shows promise in the treatment of critical limb ischemia; however, its potential for myonephropathic metabolic syndrome (MNMS), a fatal complication caused by arterial reconstruction, has not been elucidated. The objective of this study was to evaluate the effectiveness of recombinant Sendai virus-mediated gene transfer of fibroblast growth factor-2 (FGF-2) directly compared with that of a radical scavenger, MCI-186, in a rat model of MNMS. MNMS was surgically induced by aortic occlusion below renal arteries for 4 h, followed by 6 h of reperfusion. Administration of MCI-186 (twice; iv 5 min before induced ischemia and ip 5 min before reperfusion; 10 mg/kg, respectively), but not FGF-2 gene transfer (once, 48 h before induced ischemia), dramatically prevented the increase of serum biochemical markers as well as the edema of the gastrocnemius muscle. The effect of MCI-186 was accompanied by the marked suppression of the neutrophilic infiltration into the local (muscle) and remote (lung) organs. Although serum and muscular levels of a neutrophil-chemoattractant (growth-related oncogene/cytokine-induced neutrophil chemoattractant-1) were not affected by any treatment, the serum level of soluble intercellular adhesion molecule-1 was decreased by treatment with MCI-186 but not by treatment with FGF-2. These results suggest the distinct mechanism of MNMS from critical limb ischemia without reperfusion. Therefore, radical scavenging should be paid more attention than therapeutic angiogenesis when arterial circulation is reconstructed.
AB - The therapeutic use of angiogenic factors shows promise in the treatment of critical limb ischemia; however, its potential for myonephropathic metabolic syndrome (MNMS), a fatal complication caused by arterial reconstruction, has not been elucidated. The objective of this study was to evaluate the effectiveness of recombinant Sendai virus-mediated gene transfer of fibroblast growth factor-2 (FGF-2) directly compared with that of a radical scavenger, MCI-186, in a rat model of MNMS. MNMS was surgically induced by aortic occlusion below renal arteries for 4 h, followed by 6 h of reperfusion. Administration of MCI-186 (twice; iv 5 min before induced ischemia and ip 5 min before reperfusion; 10 mg/kg, respectively), but not FGF-2 gene transfer (once, 48 h before induced ischemia), dramatically prevented the increase of serum biochemical markers as well as the edema of the gastrocnemius muscle. The effect of MCI-186 was accompanied by the marked suppression of the neutrophilic infiltration into the local (muscle) and remote (lung) organs. Although serum and muscular levels of a neutrophil-chemoattractant (growth-related oncogene/cytokine-induced neutrophil chemoattractant-1) were not affected by any treatment, the serum level of soluble intercellular adhesion molecule-1 was decreased by treatment with MCI-186 but not by treatment with FGF-2. These results suggest the distinct mechanism of MNMS from critical limb ischemia without reperfusion. Therefore, radical scavenging should be paid more attention than therapeutic angiogenesis when arterial circulation is reconstructed.
UR - http://www.scopus.com/inward/record.url?scp=33646102687&partnerID=8YFLogxK
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U2 - 10.1152/ajpheart.01006.2005
DO - 10.1152/ajpheart.01006.2005
M3 - Article
C2 - 16301206
AN - SCOPUS:33646102687
VL - 290
SP - H1484-H1492
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 4
ER -