Subnormal shear stress-induced intimal thickening requires medial smooth muscle cell proliferation and migration.
Arterial intimal thickening is consisted of predominately smooth muscle cells (SMC). The source of these SMCs and mechanisms response for their changes have not been well cleared. Using a model of rabbit common carotid artery (CCA) shear induced intimal thickening, we sought to identify and describe the source of SMCs in intima. The enlarged CCA 28 days after arteriovenous fistula (AVF) creation was subjected to subnormal wall shear stress (WSS) for 1, 3, and 7 days by closure of the AVF. To determine SMC proliferation, BrdU pulse labeling of SMCs was performed. BrdU-labeled SMCs were tracked over time to further confirm SMC migration. In response to subnormal WSS intimal thickening developed progressively. BrdU-labeled SMCs localized in the subendothelial area. When the BrdU-labeled medial SMCs were tracked 1 day after AVF closure, progenies of these BrdU-incorporated SMCs increased by 4.8-fold with 75% of them in the intima. They were 12-fold increased with 83% in the intima 7 days after. En face examination showed an accumulation of SMCs in internal elastic lamina gap after AVF closure, which later migrated into subendothelial area. In situ hybridization revealed increased TGF-beta1 mRNA expression in intimal SMCs. This study demonstrates that the medial SMCs are the predominant cells in subnormal WSS-induced intimal thickening. Early expression of TGF-beta1 may play an important role in the process of intimal thickening.
Sho
Mien
M
Second Department of Pathology, Akita University School of Medicine, Akita 010-8543, Japan.
Sho
Eiketsu
E
Singh
Tej M
TM
Komatsu
Masayo
M
Sugita
Akihiro
A
Xu
Chengpei
C
Nanjo
Hiroshi
H
Zarins
Christopher K
CK
Masuda
Hirotake
H
D000222:Adaptation, Physiological; D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D002465:Cell Movement / Q000502:physiology; D004195:Disease Models, Animal; D006965:Hyperplasia / Q000209:etiology / Q000473:pathology; D017403:In Situ Hybridization; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D012039:Regional Blood Flow; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D017539:Tunica Intima / Q000473:pathology* / Q000502:physiology
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1