Development of novel technology for the visualization and quantitation of angiogenesis and the alveolar-capillary network in a mouse model of fibrosis.

Abstract

Adaptive angiogenesis can drive repair or underlie the pathogenesis of tissue remodeling. Pulmonary vascular dysfunction is a major manifestation of chronic lung disease (CLD), but the role of angiogenesis in the development of CLD is not well defined. Microvascular capillaries in the alveolar-capillary network are the vessels most affected by pruning and remodeling in the lung, resulting in reduced capillary length and diameter with subsequent loss of gas exchange surfaces. Our lab has previously demonstrated that microvascular endothelial progenitor cells (mvEPCs) drive reparative angiogenesis. We hypothesize that visualization of the alveolar-capillary microvasculature in three-dimensions is essential to define the mechanisms governing repair versus progression to the pathogenesis of CLD. To address this gap in knowledge, we have developed a simple and reliable fluorescent perfusion technique that will allow the quantitation of microvessel structure in the alveolar-capillary network using mouse models of lung injury. This approach may be used in various organ systems to visualize microvasculature structure and its role in disease.We developed and validated a fluorescent technology to visualize and quantify the alveolar-capillary network in three-dimensions in mouse lung for modeling of the microvasculature in models of lung disease.