An angiogenesis inhibitor TNP-470 (AGM-1470) suppresses vascular smooth muscle cell proliferation in experimental rat aortotomy models.
OBJECTIVE
Vascular intimal hyperplasia is an important clinical concern in vascular diseases, such as anastomotic stricture as a possible complication of cardiovascular surgery. We recently suggested that a rat aortotomy model could be substituted for a vascular anastomotic stricture around a suture line. TNP-470 is known as an angiogenesis inhibitor and has demonstrated abilities to inhibit DNA synthesis of smooth muscle cells (SMCs) and SMCs proliferation. The aim of this study was to investigate the effect of TNP-470 on SMC proliferation using rat aortotomy models.


METHODS
Longitudinal aortotomy was performed in the abdominal aorta of rats. Rats received a subcutaneous injection of materials (TNP-470, 20 mg/kg) or vehicle 3 times a week (n=10 in each group). The aorta was harvested 2 weeks after aortotomy. Serial sections from tissues were stained with hematoxylin and eosin, and the ratio of intimal to medial cross-sectional areas (I/M ratio) was determined. Values are expressed as the mean +/- the standard deviation. Results. Thickening of the intimal layer 2 weeks following aortotomy was observed in the control group however, intimal thickening was inhibited in the TNP-treated group. The I/M ratio was significantly (p = 0.0376) lower in the TNP-treated group than in the control group (8.3 +/- 4.8 vs 15.6 +/- 9.6%). Conclusion. TNP-470 significantly suppressed intimal thickening in experimental rat aortotomy models. TNP-470 might inhibit the development of anastomotic stricture after cardiovascular surgery.
Ogata
T
T
Department of Surgery, Public Tomioka General Hospital, Tomioka, Japan. toshi-ogata@gem.hi-ho.ne.jp
Kurabayashi
M
M
Maeno
T
T
Maeno
Y
Y
Ishikawa
S
S
Takeyoshi
I
I
Morishita
Y
Y
Nagai
R
R
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology* / Q000601:surgery; D001707:Biopsy, Needle; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003510:Cyclohexanes; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011336:Probability; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D012717:Sesquiterpenes / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol