Validation of the vitronectin knockout mouse as a model for studying myocardial infarction: Vitronectin appears to influence left ventricular remodelling following myocardial infarction.

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.

Versican: signaling to transcriptional control pathways.

Versican, a chondroitin sulfate proteoglycan, is one of the main components of the extracellular matrix, which provides a loose and hydrated matrix during key events in development and disease. Versican participates in cell adhesion, proliferation, migration, and angiogenesis, and hence plays a central role in tissue morphogenesis and maintenance. In addition, versican contributes to the development of a number of pathologic processes including atherosclerotic vascular diseases, cancer, tendon remodeling, hair follicle cycling, central nervous system injury, and neurite outgrowth. Versican is a complex molecule consisting of modular core protein domains and glycosaminoglycan side chains, and there are various steps of synthesis and processes regulating them. Also, there is differential temporal and spatial expression of versican by multiple cell types and in different developmental and pathological time frames. To fully appreciate the functional roles of versican as it relates to changing patterns of expression in development and disease, an in depth knowledge of versican's biosynthetic processing is necessary. The goal of this review is to evaluate the current status of our knowledge regarding the transcriptional control of versican gene regulation. We will be focusing on the signal transduction pathways, promoter regions, cis-acting elements, and trans-factors that have been characterized.

Methods for examining stem cells in post-ischemic and transplanted hearts.

Currently, the tenet that heart muscle cells are terminally differentiated and incapable of self-repair is being challenged. Recent experimental observations suggest that both endogenous and exogenous stem cell populations have the potential to regenerate damaged areas within the heart. These findings hold promise for new therapeutic strategies to treat cardiovascular diseases, including common conditions like myocardial infarction and transplant vascular disease (TVD). In this chapter, we focus on the study of endogenous stem cells in the context of their role in modulation of cardiovascular diseases, including ischemic heart disease and TVD. Specific experimental models and methods used to study the phenomena of endogenous bone marrow-derived stem cell migration and potential differentiation are also described.