BACKGROUND: Extracellular matrix (ECM) remodeling is central to the development of restenosis after PTCA. Substantial evidence implicates transforming growth factor-beta1 (TGF-beta1), a regulator of ECM deposition by vascular cells, in its pathogenesis. TGF-beta3 reduces TGF-beta1-induced ECM deposition in cutaneous wounds. We therefore investigated the effects of intracoronary expression of TGF-beta3 and TGF-beta1 on luminal loss after angioplasty. METHODS AND RESULTS: Porcine coronary arteries received an adenovirus expressing TGF-beta3, TGF-beta1, or lacZ (beta-galactosidase), or PBS only, at the site of angioplasty. Morphometric analysis 28 days after angioplasty confirmed reduced luminal loss in TGF-beta3 vessels (-0.65+/-0.10 mm2) compared with lacZ (-1.18+/-0.19 mm2) or PBS only (-1.19+/-0.17 mm2; P=0.003). Luminal loss was not reduced in TGF-beta1 vessels (-1.02+/-0.19 mm2; P=0.48). An increase in the external elastic lamina area in TGF-beta3-treated vessels (+0.73+/-0.32 mm2) contrasted with decreases in control vessels (mean, -0.53+/-0.17 mm2; P=0.001) and TGF-beta1 vessels (-0.87+/-0.34 mm2; P=0.003). Collagen content increased at the site of injury in TGF-beta3-treated vessels (26.1+/-14.2%) but decreased in the lacZ (-22.8+/-6.6%) and PBS-only (-23.4+/-7.0%; P=0.002) groups and was not significantly changed in TGF-beta1-treated vessels. CONCLUSIONS: Expression of TGF-beta3 inhibits constrictive remodeling after PTCA and reduces luminal loss. This is accompanied by increased adventitial collagen, which may act as an external "scaffold" preventing vessel constriction. These findings confirm the potential of gene therapies that modify ECM remodeling for prophylaxis of restenosis.
BACKGROUND: Extracellular matrix (ECM) remodeling is central to the development of restenosis after PTCA. Substantial evidence implicates transforming growth factor-beta1 (TGF-beta1), a regulator of ECM deposition by vascular cells, in its pathogenesis. TGF-beta3 reduces TGF-beta1-induced ECM deposition in cutaneous wounds. We therefore investigated the effects of intracoronary expression of TGF-beta3 and TGF-beta1 on luminal loss after angioplasty. METHODS AND RESULTS: Porcine coronary arteries received an adenovirus expressing TGF-beta3, TGF-beta1, or lacZ (beta-galactosidase), or PBS only, at the site of angioplasty. Morphometric analysis 28 days after angioplasty confirmed reduced luminal loss in TGF-beta3 vessels (-0.65+/-0.10 mm2) compared with lacZ (-1.18+/-0.19 mm2) or PBS only (-1.19+/-0.17 mm2; P=0.003). Luminal loss was not reduced in TGF-beta1 vessels (-1.02+/-0.19 mm2; P=0.48). An increase in the external elastic lamina area in TGF-beta3-treated vessels (+0.73+/-0.32 mm2) contrasted with decreases in control vessels (mean, -0.53+/-0.17 mm2; P=0.001) and TGF-beta1 vessels (-0.87+/-0.34 mm2; P=0.003). Collagen content increased at the site of injury in TGF-beta3-treated vessels (26.1+/-14.2%) but decreased in the lacZ (-22.8+/-6.6%) and PBS-only (-23.4+/-7.0%; P=0.002) groups and was not significantly changed in TGF-beta1-treated vessels. CONCLUSIONS: Expression of TGF-beta3 inhibits constrictive remodeling after PTCA and reduces luminal loss. This is accompanied by increased adventitial collagen, which may act as an external "scaffold" preventing vessel constriction. These findings confirm the potential of gene therapies that modify ECM remodeling for prophylaxis of restenosis.
Authors: Shakti A Goel; Lian-Wang Guo; Xu-Dong Shi; Rishi Kundi; Gregory Sovinski; Stephen Seedial; Bo Liu; K Craig Kent Journal: Cell Signal Date: 2012-12-29 Impact factor: 4.315
Authors: Rishi Kundi; Scott T Hollenbeck; Dai Yamanouchi; Brad C Herman; Rachel Edlin; Evan J Ryer; Chunjie Wang; Shirling Tsai; Bo Liu; K Craig Kent Journal: Cardiovasc Res Date: 2009-07-01 Impact factor: 10.787
Authors: Shakti A Goel; Lian-Wang Guo; Bowen Wang; Song Guo; Drew Roenneburg; Gene E Ananiev; F Michael Hoffmann; K Craig Kent Journal: PLoS One Date: 2014-02-24 Impact factor: 3.240