Gordon E Pate1, Hubert P Walinski, Lubos Bohunek, Thomas J Podor. 1. Department of Pathology and Laboratory Medicine, University of British Columbia and the James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St Paul's Hospital, Vancouver, British Columbia.
Abstract
BACKGROUND: Vitronectin (VN) is an abundant acute-phase plasma protein that regulates cell adhesion and migration as well as interactions with components of the plasminogen activator/plasmin system, specifically plasminogen activator inhibitor type 1. This system plays a major role in tissue remodelling regulating wound healing after myocardial infarction. OBJECTIVES: To investigate the feasibility of using VN knockout mice (VN(-/-)) to study the role of VN on ventricular remodelling following myocardial infarction. METHODS: Specifically bred VN(-/-) mice and normal wild-type (VN(+/+)) mice underwent coronary artery ligation and were assessed 28 days postligation using echocardiography and morphometric histology. RESULTS: No difference was observed between VN(-/-) mice and VN(+/+) mice with respect to gross phenotype, weight, coronary anatomy or echocardiographically measured ejection fraction (56%). Following myocardial infarction, VN(-/-) mice exhibited less ventricular dilation and less impairment in echocardiographic ejection fraction compared with VN(+/+) mice (48% versus 41%; P=0.01). VN(-/-) mice also exhibited smaller infarcts on morphometric analysis. CONCLUSIONS: The results of the present study confirmed the feasibility of using coronary artery ligation in VN knockout mice to investigate the role of VN in post-myocardial infarction remodelling. The absence of VN appears to result in favourable effects on wound healing. These data suggest that this model may offer novel insights into the role of VN in the regulation of myocardial remodelling.
BACKGROUND:Vitronectin (VN) is an abundant acute-phase plasma protein that regulates cell adhesion and migration as well as interactions with components of the plasminogen activator/plasmin system, specifically plasminogen activator inhibitor type 1. This system plays a major role in tissue remodelling regulating wound healing after myocardial infarction. OBJECTIVES: To investigate the feasibility of using VN knockout mice (VN(-/-)) to study the role of VN on ventricular remodelling following myocardial infarction. METHODS: Specifically bred VN(-/-) mice and normal wild-type (VN(+/+)) mice underwent coronary artery ligation and were assessed 28 days postligation using echocardiography and morphometric histology. RESULTS: No difference was observed between VN(-/-) mice and VN(+/+) mice with respect to gross phenotype, weight, coronary anatomy or echocardiographically measured ejection fraction (56%). Following myocardial infarction, VN(-/-) mice exhibited less ventricular dilation and less impairment in echocardiographic ejection fraction compared with VN(+/+) mice (48% versus 41%; P=0.01). VN(-/-) mice also exhibited smaller infarcts on morphometric analysis. CONCLUSIONS: The results of the present study confirmed the feasibility of using coronary artery ligation in VN knockout mice to investigate the role of VN in post-myocardial infarction remodelling. The absence of VN appears to result in favourable effects on wound healing. These data suggest that this model may offer novel insights into the role of VN in the regulation of myocardial remodelling.
Authors: Thomas J Podor; Davindra Singh; Paul Chindemi; Denise M Foulon; Robert McKelvie; Jeffrey I Weitz; Richard Austin; Ghislain Boudreau; Richard Davies Journal: J Biol Chem Date: 2001-12-14 Impact factor: 5.157
Authors: Michael H Lazar; Paul J Christensen; Ming Du; Bi Yu; Natalya M Subbotina; Kerstin E Hanson; Jean M Hansen; Eric S White; Richard H Simon; Thomas H Sisson Journal: Am J Respir Cell Mol Biol Date: 2004-08-12 Impact factor: 6.914
Authors: Arman T Askari; Marie-Luise Brennan; Xiaorong Zhou; Jeanne Drinko; Annitta Morehead; James D Thomas; Eric J Topol; Stanley L Hazen; Marc S Penn Journal: J Exp Med Date: 2003-03-03 Impact factor: 14.307