Often, we test hypotheses regarding mechanobiological mechanisms of disease progression in the absence of an intact physiological system. These in vitro or cell culture studies yield insights into the effects of mechanical stimuli, such as shear stress and cyclic stretch, on endothelial cell biology. This approach also gives exquisite control over the cell chemical environment, source of cells, and allows imaging and cytokine readouts coincident with mechanical stimulation. We are currently using in vitro approaches to study the mechanobiological mechanisms of transition from isolated post-capillary pulmonary hypertension to combined pre/post capillary pulmonary hypertension.