Vascular smooth muscle cell proliferation is dependent upon upregulation of mitochondrial transcription factor A (mtTFA) expression in injured rat carotid artery.
Consistent with the physiological response to increased energy demand in proliferating cells, the number of mitochondria is upregulated in synthetic states of vascular smooth muscle cells (VSMC) in atherosclerotic lesion. We hypothesized that mitochondrial transcription factor A (mtTFA), a prerequisite factor for the transcription and replication of mtDNA, may be upregulated in VSMC of injured rat carotid artery, and that inhibition of its expression can attenuate the intimal thickening. Changes of intimal thickening and mtTFA expression by a treatment with antisense oligodeoxynucleotides (ODN) for mtTFA were investigated in balloon-injured rat carotid artery model. The expression of mtTFA was upregulated as early as 3 h up to 7 days after balloon injury. Delivery of ansisense ODN for mtTFA from adventitia side to injured arterial wall caused a significant decrease in intima-to-media (I/M) ratio. Furthermore, the increase in immunoreactivity and mRNA expression of mtTFA in injured artery as well as the number of mitochondria in intimal VSMC was abrogated by antisense ODN treatment. These data demonstrate that expression of mtTFA is upregulated in intimal VSMC of injured rat carotid artery, and that suppression of mtTFA expression by antisense ODN can attenuate intimal thickening after balloon injury.
Yoshida
Tomonori
T
Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Azuma
Hiroyuki
H
Aihara
Ken-ichi
K
Fujimura
Mitsunori
M
Akaike
Masashi
M
Mitsui
Takao
T
Matsumoto
Toshio
T
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D002404:Catheterization; D049109:Cell Proliferation; D004272:DNA, Mitochondrial / Q000037:antagonists & inhibitors; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000473:pathology*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; C489030:Tfam protein, rat; D014157:Transcription Factors; C422562:mitochondrial transcription factor A