Multi-cellular Kinetics and Tissue Remodeling Visualized by in vivo Molecular Imaging
Abstract: To assess physiological and pathophysiological events that involve dynamic interplay between multiple cell-types such as inflammation and atherosclerosis, real-time and three-dimensional analysis of cell dynamics in vivo is required. We developed a visualization technique based on confocal laser microscopy that enabled us to analyze the three-dimensional structures and cellular dynamics in vivo with high spatiotemporal resolution (2007 Diabetes, 2008 JCI). We applied this technique to visualize cellular interplay in adipose tissue obesity to elucidate the mechanism of metabolic syndrome, a major cause of cardiovascular disease.
We found close spatial and temporal interrelationships between angiogenesis and adipogenesis, and both were augmented in obese animals. In the microcirculation of obese visceral adipose tissue, we also found increased leukocyte-platelet-endothelial cell interactions, which were indicative of activation of the leukocyte adhesion cascade, a hallmark of inflammation. Platelets were also activated locally in obese visceral adipose. Our results clearly demonstrated the power of our imaging technique to analyze complex cellular interplays in vivo and to evaluate new therapeutic interventions against them. Results also indicate that visceral adipose tissue obesity is an inflammatory disease.
Key words: in vivo imaging, inflammation, obesity, adipose tissue