FIGURE 9.

Juxtacrine signaling among pulmonary vascular endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts (FBs) may contribute to spread “pathogenic signals.” A: schematic diagram showing the proposed scenario in which a single cell in normal pulmonary artery (PA) may become an affected cell or a “diseased” cell by, for example, somatic mutation and stimulation through localized pathogenic factors. B: the “diseased cell” then spreads the pathogenic signals to adjacent cells through juxtacrine signaling mechanisms to affect other cells in close vicinity. C: the pathogenic communication or interaction among the affected cells eventually forms the local lesion that can further develop and expand and, ultimately, affect the function and structure of the segment of the pulmonary vasculature, especially in the presence of inflammatory cells and pathogenic progenitor cells. ECM, extracellular matrix.