Transforming growth factor-beta 1 expression and myofibroblast formation during arterial repair.
Transforming growth factor-beta 1 (TGF-beta 1) plays a central role in tissue repair owing to its modulating effects on cell growth and the synthesis of extracellular matrix. We have previously shown that adventitial fibroblasts differentiate to myofibroblasts after endoluminal injury, thereby contributing to arterial remodeling. Since TGF-beta 1 exerts several biologic actions attributed to myofibroblasts, we examined its role in myofibroblast formation in a porcine model of balloon overstretch coronary artery injury. TGF-beta 1 transcripts were induced in numerous adventitial cells 2 days after injury (47 +/- 10%, P < .001 versus control). These cells displayed no smooth muscle (SM) markers, i.e., alpha-SM actin or desmin, which suggested their fibroblastic origin. This was further corroborated by the rare presence of macrophages in the injured adventitia (3 +/- 1%). At 7 to 8 days, most TGF-beta 1-expressing cells demonstrated alpha-SM actin immunoreactivity. Their myofibroblast phenotype was confirmed by electron microscopy, which revealed microfilaments (stress fibers) and a well-developed rough endoplasmic reticulum. The distribution of TGF-beta 1 transcripts by in situ hybridization was paralleled by the immunolocalization of intracellular and extracellular TGF-beta 1 epitopes. At later times (> 14 days after injury), the decrease in TGF-beta 1 coincided with the disappearance of adventitial myofibroblasts, whereas the neointima exhibited longer TGF-beta 1 expression. In conclusion temporal and spatial relationships between TGF-beta 1 and myofibroblast formation suggest an important role for autocrine TGF-beta 1 in the phenotypic modulation of vascular fibroblasts. Induction of TGF-beta 1 expression may provide a differentiation signal for adventitial fibroblasts to become myofibroblasts, which affect arterial remodeling via their mechanical and synthetic properties.
Shi
Y
Y
Department of Medicine (Cardiology), Thomas Jefferson University, Philadelphia, Pa 19107, USA.
O'Brien
J E
JE
Fard
A
A
Zalewski
A
A
D000818:Animals; D002404:Catheterization; D002454:Cell Differentiation; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology*; D005347:Fibroblasts / Q000473:pathology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008854:Microscopy, Electron; D013552:Swine; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D016212:Transforming Growth Factor beta